Toxicological effects of thimerosal on rat kidney: a histological and biochemical study / Efeitos toxicológicos do timerosal no rim de rato: um estudo histológico e bioquímico

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.

Study on the difference of curative effect of conventional mercury displacement treatment on mercury in brain and kidney / 中华劳动卫生职业病杂志

Objective: To explore the expulsion effect of sodium dimercaptopropanesulfonate (DMPS) on mercury in different organs of mercury poisoning and the therapeutic effect of glutathione (GSH) combined with antioxidant therapy on mercury poisoning. Methods: In February 2019, 50 SPF male SD rats were randomly divided into 5 groups, 10 rats in each group: A (saline negative control group) , B (HgCL2 positive control group) , treatment group (C: intramuscular injection of DMPS 15 mg/kg treatment, D: intramuscular injection of DMPS30 mg/kg treatment, E: intramuscular injection of DMPS 15 mg/kg and intraperitoneal injection of GSH200 mg/kg treatment) . Rats in group B, C, D and E were subcutaneously injected with mercury chloride solution (1 mg/kg) to establish a rat model of subacute mercury poisoning kidney injury. Rats in group A were subcutaneously injected with normal saline. After the establishment of the model, rats in the treatment group were injected with DMPS and GSH. Rats in group A and group B were injected with normal saline. At 21 d (treatment 7 d) and 28 d (treatment 14 d) after exposure, urine and blood samples of 5 rats in each group were collected. Blood biochemistry, urine mercury, urine microalbumin and mercury content in renal cortex, cerebral cortex and cerebellum were detected. Results: After exposure to mercury, the contents of mercury in renal cortex, cerebrum and cerebellum of rats in group B, C, D and E increased, and urine microalbumin increased. Pathology showed renal tubular injury and renal interstitial inflammation. Compared with group B, urinary mercury and renal cortex mercury in group C, D and E decreased rapidly after DMPS treatment, and there was no significant decrease in mercury levels in cerebellum and cerebral cortex of rats, accompanied by transient increase in urinary albumin after DMPS treatment (P<0.05) ; the renal interstitial inflammation in group E was improved after GSH treatment. There was a positive correlation between urinary mercury and the contents of mercury in renal cortex, cerebral cortex and cerebellum (r=0.61, 0.47, 0.48, P<0.05) . Conclusion: DMPS mercury expulsion treatment can significantly reduce the level of metal mercury in the kidney, and there is no significant change in the level of metal mercury in the cortex and cerebellum.

Swim training reverses some effects of nandrolone decanoate in wistar rats / El entrenamiento en natación revierte algunos efectos del decanoato de nandrolona en los ratones wistar / Treinamento de natação reverte alguns efeitos do decanoato de nandrolona em ratos wistar

ABSTRACT Introduction: The indiscriminate use of androgenic steroids may have deleterious effects on human tissue. Objectives: Evaluate the effects of chronic administration of the steroid nandrolone decanoate (DECA) on autonomic cardiovascular modulation, kidney morphometry and the association between these variables in Wistar rats subjected to physical training with swimming. Methods: Thirty-two male Wistar rats aged 20 weeks were distributed among four experimental groups according to the training received: sedentary control (SC), sedentary treated with DECA (SD), trained control (TC) and trained treated with DECA (TD). The hemodynamic parameters, including blood pressure and variations in systolic blood pressure (SBPV) and diastolic blood pressure (DBPV), and kidney morphometry were evaluated. The level of significance adopted was 5%. Results: The SD group had higher baseline SBP and DBP values when compared to the SC, TC and TD groups, which were similar to each other. The rats in the SD group had higher systolic blood pressure (SBPV) and diastolic blood pressure (DBPV) variation values and higher absolute and normalized values in the LF band of the DBPV when compared to the animals in the SC, TC and TD groups. The animals in the SD group had a significantly higher rate of kidney fibrosis compared to the SC, TC and TD groups. There were no significant differences between the sympathetic modulation of SBPV through the LF component and kidney fibrosis. Conclusions: Physical training with swimming was effective in preventing the increase in blood pressure levels and lowering the occurrence of kidney fibrosis in animals treated with anabolic steroids. Level of Evidence IV; Series of cases .

RESUMEN Introducción: El uso indiscriminado de esteroides androgénicos puede tener consecuencias nocivas para el organismo. Objetivo: Evaluar los efectos de la administración crónica del esteroide decanoato de nandrolona (DECA) en ratones Wistar sometidos a entrenamiento físico con natación, sobre la modulación autonómica cardiovascular, morfometría renal y asociación entre esas variables. Métodos: Fueron utilizados 32 ratones Wistar machos con edad de 20 semanas, distribuidos en 4 grupos experimentales de acuerdo con el tratamiento recibido: sedentarios controles (SC), sedentarios que recibieron el DECA (SD), entrenados controles (EC) y entrenados que recibieron el DECA (ED). Se evaluaron parámetros hemodinámicos, como presión arterial y variación de la presión arterial sistólica (VPAS) y diastólica (VPAD) y morfometría renal. El nivel de significancia adoptado fue de 5%. Resultados: El grupo SD presentó valores basales mayores de PAS y PAD cuando comparados a los grupos SC, EC y ED, los cuales fueron semejantes entre sí. Los animales del grupo SD tuvieron valores mayores de la variancia de VPAS y VPAD y valores absolutos mayores y normalizados de la banda LF de la VPAD, en comparación con los animales de los grupos SC, EC y ED. El grupo SD tuvo tasa significativamente mayor de fibrosis renal en comparación con los animales de los grupos SC, EC y ED. No se evidenciaron diferencias considerables entre la modulación simpática de la VPAS a través del componente LF y fibrosis renal. Conclusiones: El entrenamiento físico con natación fue efectivo en prevenir el aumento de niveles presóricos y disminuir la ocurrencia de fibrosis renal en animales tratados con esteroide anabolizante. Nivel de Evidencia IV; Serie de casos .

RESUMO Introdução: O uso indiscriminado de esteroides androgênicos pode ter consequências deletérias no organismo. Objetivo: Avaliar os efeitos da administração crônica do esteroide decanoato de nandrolona (DECA) em ratos Wistar submetidos a treinamento físico com natação sobre a modulação autônoma cardiovascular, morfometria renal e associação entre essas variáveis. Métodos: Foram utilizados 32 ratos Wistar machos com idade de 20 semanas, distribuídos em 4 grupos experimentais de acordo com o tratamento recebido: sedentários controles (SC), sedentários que receberam o DECA (SD), treinados controles (TC) e treinados que receberam o DECA (TD). Avaliaram-se parâmetros hemodinâmicos, como pressão arterial e variação da pressão arterial sistólica (VPAS) e diastólica (VPAD) e morfometria renal. O nível de significância adotado foi de 5%. Resultados: O grupo SD apresentou valores basais maiores de PAS e PAD quando comparado aos grupos SC, TC e TD, os quais foram semelhantes entre si. Os animais do grupo SD tiveram valores maiores da variância da VPAS e VPAD e valores absolutos maiores e normalizados da banda LF da VPAD, em comparação com os animais dos grupos SC, TC e TD. O grupo SD teve taxa significativamente maior de fibrose renal em comparação com os animais dos grupos SC, TC e TD. Não se evidenciaram diferenças consideráveis entre a modulação simpática da VPAS através do componente LF e fibrose renal. Conclusões: O treinamento físico com natação foi efetivo em prevenir o aumento de níveis pressóricos e diminuir a ocorrência de fibrose renal em animais tratados com esteroide anabolizante. Nível de Evidência IV; Série de casos .

Prevalência de nefropatia induzida por contraste em pacientes cardíacos de um setor de hemodinâmica / Prevalence of contrast-induced nephropathy in cardiac patients in a hemodynamic sector / Prevalencia de nefropatía inducida por contraste en pacientes cardíacos de un sector de hemodinámica

Objetivo: Determinar a prevalência da nefropatia induzida por contraste em pacientes cardiopatas submetidos a procedimentos angiográficos de diagnóstico e/ou tratamento. Método: Estudo prospectivo, quantitativo, realizado no setor de hemodinâmica de um hospital de grande porte, situado na região norte do Rio Grande do Sul, Brasil. A amostra foi constituída por 79 participantes através do cálculo de tamanho amostral. Resultados: A amostra foi formada por 52 (65,8%) homens e 27 (34,2%) mulheres. A idade média foi de 65,9 ± 9,52 anos. A incidência de nefropatia induzida por contraste foi de 30,38%, totalizando 24 pacientes. Conclusão: Foi evidenciada uma alta prevalência de nefropatia por contraste, apesar dos pacientes apresentarem poucos fatores de risco, o que ressalta a necessidade de medidas preventivas e redução do volume de contraste

Objective: To determine the prevalence of contrast-induced nephropathy in cardiac patients undergoing diagnostic and / or treatment angiographic procedures. Method: A prospective, quantitative study in the hemodynamics sector of a large hospital, located in the northern region of Rio Grande do Sul, Brazil. The sample consisted of 79 participants through the calculation of sample size. Results: The sample consisted of 52 (65.8%) men and 27 (34.2%) women. The mean age was 65.9 ± 9.52 years. The incidence of contrast-induced nephropathy was 30,38%, totaling 24 patients. Conclusion: A high prevalence of contrast nephropathy was evidenced, despite the fact that patients presented few risk factors, which highlights the need for preventive measures and reduction of contrast volume

Objetivo: Determinar la prevalencia de la nefropatía inducida por contraste en pacientes cardiopatas sometidos a procedimientos angiográficos de diagnóstico y / o tratamiento. Método: Estudio prospectivo, cuantitativo, realizado en el sector de hemodinámica de un hospital de gran porte, situado en la región norte de Rio Grande do Sul, Brasil. La muestra fue constituida por 79 participantes a través del cálculo de tamaño muestral. Resultados: La muestra fue formada por 52 (65,8%) hombres y 27 (34,2%) mujeres. La edad media fue de 65,9 ± 9,52 años. La incidencia de nefropatía inducida por contraste fue del 30,38%, totalizando 24 pacientes. Conclusión: Se evidenció una alta prevalencia de nefropatía por contraste, a pesar de que los pacientes presentaban pocos factores de riesgo, lo que resalta la necesidad de medidas preventivas y reducción del volumen de contraste

Renoprotective Effects of Gallic Acid Against Gentamicin Nephrotoxicity Through Amelioration of Oxidative Stress in Rats

Abstract Gallic acid (GA), as a strong antioxidant, was selected in this study to investigate its possible nephroprotective effects against gentamicin (GM)-induced nephrotoxicity. Twenty-four rats were separated into three groups (n=8): group 1 (control group) received saline (0.5 mL/day), group 2 (GM group) received GM (100 mg/kg/day), and group 3 (treated group) received GM (100 mg/kg/day) and GA (100mg/kg/day). All treatments were performed intraperitoneally for 12 days. After 12 days, the rats were euthanized, and kidneys were removed immediately. For serum preparation, blood samples were collected before killing. Kidney paraffin sections were prepared from one of the kidneys and stained by the periodic acid-Schiff process. GA significantly decreased GM-induced renal histopathological injuries, including tubular necrosis, tubular cast, and leucocyte infiltration compared with the GM group. Additionally, GA significantly improved proteinuria, serum levels of urea and creatinine, and serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with nephrotoxic animals. Furthermore, GA caused a significant improvement in the levels of cholesterol (Chol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and cardiac risk ratios 1 and 2 in comparison with nephrotoxic animals. GA administration was observed to significantly improve the levels of lipid peroxidation, nitric oxide (NO), and glutathione (GSH) compared with the GM group. Finally, the activities and gene expression levels of catalase (CAT) and glutathione peroxidase (GPX) significantly increased following GA administration compared with the GM group. Our results indicated that GA has potential protective effects against GM nephrotoxicity by reducing oxidative stress in rats.

Estudo da morfologia e status oxidativo em rim de ratos com nefropatia isquêmica após tratamento com células-tronco mesenquimais de tecido adiposo / Study of morphology and oxidative status in kidney of rats with ischemic nephropathy after treatment with adipose tissue mesenchymal stem cells

A nefropatia isquêmica é uma doença renal crônica provocada pela redução do fluxo sanguíneo renal que pode progredir para a doença renal terminal, cujo tratamentos disponíveis se baseiam em terapias substitutivas da função renal, como diálise ou transplante renal. No entanto, devido ao alto custo dos tratamentos e a carência de órgãos, se faz necessária a busca por novas terapias, como as células-tronco (CT). Apesar do potencial terapêutico das CT em doenças crônicas, não está claro se essas células mantêm seus efeitos benéficos em órgãos lesionados por tempo prolongado. O objetivo desse estudo foi avaliar os efeitos precoces e tardios do tratamento com células-tronco adiposas (CTA) sobre a morfologia e o status oxidativo em rins de ratos com nefropatia isquêmica. A isquemia renal foi induzida pelo modelo 2rins-1clip (2R1C) e, depois de um mês da clipagem da artéria renal, foram injetadas 106 células-tronco na região subscapsular do rim afetado. Após 15 e 30 dias da injeção das CTA, a morfologia renal foi verificada por meio da análise macroscópica, microscópica e ultraestrutural. Além disso, o status oxidativo foi avaliado no tecido renal através da mensuração da atividade das enzimas antioxidantes catalase e glutationa peroxidase; e de marcadores biológicos de dano oxidativo, como proteínas carboniladas, 3-Nitrotirosina e 4-Hidroxinonenal. Por imunoperoxidase foi possível localizar as células-tronco adiposas GFP+ foram rastreadas e encontradas tanto 15 dias, quanto 30 dias após a injeção na região subcapsular. A restauração da arquitetura renal foi evidenciada 15d após o uso das células, onde detectamos redução na deposição de fibras colágenas no parênquima renal, o que não foi observado 30d após o uso das células. Os resultados também foram confirmados através da análise da ultraestrutura renal que mostraram restauração da arquitetura renal no grupo de 15d, não evidenciada no grupo de 30d. Quanto a análise do status oxidativo, somente os animais com nefropatia isquêmica mais prolongada apresentaram estresse oxidativo com redução da atividade da enzima antioxidante catalase no tecido renal. Além disso, foi observado dano proteico e lipídico, sem melhora dessa condição nos animais 30d após o tratamento com as células-tronco. No modelo de nefropatia isquêmica avaliado, o tratamento com CTA mostrou benefícios na morfologia renal a curto prazo, mas não tardiamente, apesar da permanência dessas células no tecido. Acreditamos que o estresse oxidativo, evidenciado somente no tecido renal com isquemia mais prolongada, possa ter dificultado a ação das células-tronco, contribuindo para tais achados. Esses resultados abrem perspectivas para o aprofundamento do estudo quanto à caracterização dos mecanimos de ação das CTA nas respostas anti-fibrogênicas, assim como o estabelecimento do número, frequência, vias de administração e melhor momento para uso dessas células no tratamento de doenças renais crônicas.

Ischemic nephropathy is a chronic kidney disease caused by reduced kidney blood flow that can progress to end stage kidney disease, whose available treatments are based on kidney function replacement therapies, such as dialysis or kidney transplantation. However, due to the high cost of treatments and the lack of organs, it is necessary to search for new therapies, such as stem cells (SC). Despite the therapeutic potential of SC in chronic diseases, it is unclear whether these cells maintain their beneficial effects on injured organs for a long time. The aim of this study was to evaluate the early and late effects of adipose-derived stem cells (ADSC) treatment on the morphology and oxidative status in kidneys of rats with ischemic nephropathy. Renal ischemia was induced by the 2kidneys-1clip (2K1C) model and, after a month of clipping the renal artery, 106 stem cells were injected into the subscapsular region of the affected kidney. After 15 and 30 days of ADSC injection, renal morphology was verified by macroscopic, microscopic, and ultrastructural analysis. In addition, oxidative status was assessed in renal tissue by measuring the activity of the antioxidant enzymes catalase and glutathione peroxidase; and biological markers of oxidative damage, such as carbonylated proteins, 3-nitrotyrosine and 4-hydroxynonenal. By immunoperoxidase, it was possible to locate GFP + adipose-derived stem cells that were tracked and found both 15 days and 30 days after injection in the subcapsular region. The restoration of the renal architecture was evidenced 15d after the use of the cells, where we detected a reduction in the deposition of collagen fibers in the renal parenchyma, which was not observed 30d after the use of the cells. The results were also confirmed by analyzing the renal ultrastructure, which showed restoration of the renal architecture in the 15d group, not evidenced in the 30d group. Regarding the analysis of oxidative status, only animals with more prolonged ischemic nephropathy presented oxidative stress with reduced activity of the antioxidant enzyme catalase in renal tissue. In addition, protein and lipid damage was observed, with no improvement in this condition in the animals 30d after treatment with stem cells. In the evaluated ischemic nephropathy model, treatment with ADSC showed benefits in renal morphology in the short term, but not late, despite the permanence of these cells in the tissue. We believe that oxidative stress, evidenced only in renal tissue with more prolonged ischemia, may have hindered the action of stem cells, contributing to such findings. These results open perspectives for further study on the characterization of ADSC mechanisms of action in anti-fibrogenic responses, as well as the establishment of the number, frequency, routes of administration and the best time to use these cells in the treatment of chronic kidney diseases.

Predictive value of ATRIA risk score for contrast-induced nephropathy after percutaneous coronary intervention for ST-segment elevation myocardial infarction

SUMMARY BACKGROUND: The AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) risk score used to detect the thromboembolic and hemorrhagic risk in atrial fibrillation patients has been shown recently to predict poor clinical outcomes in patients with acute myocardial infarction (ACS), regardless of having atrial fibrillation (AF). We aimed to analyze the relationship between different risk scores and contrast-induced nephropathy (CIN) development in patients with ACS who underwent urgent percutaneous coronary intervention (PCI) and compare the predictive ability of the ATRIA risk score with the MEHRAN risk score. METHODS: We analyzed 429 patients having St-segment Elevation Myocardial Infarction (STEMI) who underwent urgent PCI between January 2016 and February 2017. Patients were divided into two groups: those with and those without CIN and both groups were compared according to clinical, laboratory, and demographic features, including the CHA2DS2-VASc and ATRIA risk score. Predictors of CIN were determined by multivariate regression analysis. Receiver operating characteristics (ROC) curve analysis was used to analyze the prognostic value of CHA2DS2-VASc and ATRIA risk score for CIN, following STEMI. RESULTS: Multivariate regression analysis showed that Athe TRIA risk score, Opaque/Creatinine Clearance ratio, and low left ventricular ejection fraction was an independent predictor of CIN. The C-statistics for the ATRIA risk score and CHA2DS2-VASC risk score were 0.66 and 0.64 (p<0.001, and p<0.001), respectively. A pair-wise comparison of ROC curves showed that both scores were not inferior to the MEHRAN score in predicting CIN. CONCLUSION: The ATRIA and CHA2DS2-VASC scoring systems were useful for detecting CIN following STEMI.

RESUMO OBJETIVO: O escore Anticoagulação e Fatores de Risco na Fibrilação Atrial (Atria), usado na detecção do risco tromboembólico e hemorrágico de pacientes com fibrilação atrial (FA), recentemente demonstrou predizer resultados clínicos ruins em pacientes com infarto agudo do miocárdio (SCA), independentemente de ter FA. Nosso objetivo foi analisar a relação entre os diferentes escores de risco e o desenvolvimento de nefropatia induzida por contraste (NIC) em pacientes com SCA submetidos à intervenção coronária percutânea (ICP) urgente e comparar a capacidade preditiva do escore de risco Atria com o escore de risco Mehran. MÉTODOS: Foram analisados 429 pacientes com infarto agudo do miocárdio com elevação do segmento ST (IAM-ST) submetidos à ICP de urgência entre janeiro de 2016 e fevereiro de 2017. Os pacientes foram divididos em dois grupos: aqueles com e sem NIC, e ambos os grupos foram comparados de acordo com as características clínicas, laboratoriais e demográficas, incluindo os escores de risco CHA2DS2-VASc e Atria. Preditores de NIC foram determinados por análise de regressão multivariada. A análise da curva características de operação do receptor (ROC) foi utilizada para analisar o valor prognóstico dos escores de risco CHA2DS2-VASc e Atria para NIC, após IAM-ST. RESULTADOS: A análise de regressão multivariada mostrou que o escore de risco Atria, a relação opaca/crCl e a baixa fração de ejeção do ventrículo esquerdo foram preditores independentes de NIC. A estatística-C para o escore de risco Atria e o escore de risco CHA2DS2-VASC foi de 0,66 e 0,64 (p<0,001 e p<0,001), respectivamente. Uma comparação de pares de curvas características de operação do receptor mostrou que ambos os escores foram não inferiores ao escore Mehran na previsão de NIC. CONCLUSÃO: Os sistemas de pontuação Atria e CHA2DS2-VASC foram sistemas úteis para a detecção de NIC após IAM-ST.

Efectos en la función renal de la suplementación de creatina con fines deportivos / Effects of creatine supplementation on renal function

Creatine supplements may transitorily rise serum creatinine levels and mimic a kidney disease. If its use is associated with a high protein diet, the resulting increase in blood urea nitrogen will increase the confusion. Since clinical laboratories usually inform the estimated glomerular filtration rate based on serum creatinine, its elevation may lead to over diagnose a chronic renal failure, with the inherent personal and public health consequences. Creatine supplements are safe and do not cause renal disease. Reports of kidney damage associated with its use are scanty. However, creatine supplements should not be used in people with chronic renal disease or using potentially nephrotoxic medications.

New metallophamaceutic reduced renal injury induced by non-steroidal anti-inflammatory

Abstract Purpose To evaluate the effect of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor, able to modulate the histological changes caused by the NASID (meloxicam). Methods Wistar rats were assigned into three groups (n=6 rats/group): Sham group (saline solution), NSAID group (meloxicam - 15 mg/kg) and Rut-bpy group (100 mg/kg of Rut-bpy associated with 15mg/kg of meloxicam). At the end of experiments, kidneys were removed for histological study, fractal dimension and lacunarity in all animals. Results At the histological examination, all animals (six animals - 100 %) in the NSAID group had membrane thickening and other changes (necrosis, acute tubular congestion and vascular congestion); on the other hand, only one animal (16.6 %) of the Rut-bpy group had congestion. The fractal dimension and lacunarity were greater in the control and Rut-bpy group than in NSAIDs group (p<0.05). Conclusion Rut-bpy may prevent renal histological changes in rats caused by meloxicam.

Sub-chronic administration of vincristine sulfate induces renal damage and apoptosis in rats via induction of oxidative stress and activation of Raf1-MEK1/2-Erk1/2 signal transduction / La administración subcrónica de sulfato de vincristina induce daño renal y apoptosis en ratas por inducción de estrés oxidativo y activación de la transducción de señales Raf1-MEK1/2-Erk1/2

SUMMARY: In spite of being one of the most powerful anti-cancer drug, the nephrotoxicity of Vincristine (VCR) is not well established in either animals or humans. Hence, this study evaluates the nephrotoxic effect of VCR in rats after sub-chronic long-term administration. Rats were divided into 2 groups (n=10/group) of either control and VCR treated rats (50 mg/kg). Treatments were carried out for 30 consecutive days, after which a series of biochemical and molecular experiments related to kidney function were evaluated. VCR administration significantly decreased the survival rate (69.8 %) and impaired renal function as evidenced by lowered creatinine (Cr) clearance (Ccr), high serum levels of urea and Cr, increased urinary protein levels and resulted in sever cortex pathological alterations, including glomerulus congestion and damage as well as vascular degenerations up to necrosis of both proximal and distal convoluted tubules. Mechanistically, VCR lowered renal antioxidant potential and ATP levels, enhanced lipid peroxidation and induced inflammation. In addition, VCR induced activation of Raf-1-MEK1/2-ERK1/2 signaling pathway leading to downregulation of Bcl2 and upregulation of P53, Bax, and cleaved caspase-3. In conclusion, these findings show a nephrotoxic effect of VCR sulfate in rats after sub-chronic administration and such effect was mediated by activation of ERK1/2 induced apoptosis.

RESUMEN: A pesar de ser uno de los medicamentos de mayor eficacia contra el cáncer, aún no se ha establecido la nefrotoxicidad de la vincristina (VCR) en animales y humanos. Por lo tanto, este estudio evalúa el efecto nefrotóxico de la VCR en ratas después de la administración subcrónica a largo plazo. Las ratas se dividieron en 2 grupos (n = 10 / grupo) de control y ratas tratadas con VCR (50 mg / kg). Los tratamientos se llevaron a cabo durante 30 días consecutivos, después de los cuales se evaluaron una serie de experimentos bioquímicos y moleculares relacionados con la función renal. La administración de VCR disminuyó significativamente la tasa de supervivencia (69,8 %), dificultó la función renal, lo que se observó además en los bajos niveles de creatinina (Cr) (Ccr), los niveles séricos elevados de urea y Cr, un nivel más alto de proteína urinaria, los que dieron lugar a alteraciones patológicas severas de la corteza, incluido el glomérulo congestión y daño, como también degeneraciones vasculares, incluyendo la necrosis de los túbulos contorneados proximales y distales. Mecánicamente, el VCR redujo el potencial antioxidante renal y los niveles de ATP, mejoró la peroxidación lipídica y la inflamación inducida. Además, la VCR indujo la activación de la vía de señalización Raf-1-MEK1 / 2-ERK1 / 2 que conduce a la regulación negativa de Bcl-2 y la regulación positiva de P53, Bax y la caspasa-3. En conclusión, estos hallazgos muestran un efecto nefrotóxico del sulfato de VCR en ratas después de la administración subcrónica. Dicho efecto fue mediado por la activación de la apoptosis inducida por ERK1 / 2.

An experimental study on the preventive effects of N-acetyl cysteine and ozone treatment against contrast-induced nephropathy

Abstract Purpose: To compare the preventive effects of N-acetyl cysteine (NAC), ozone preconditioning and ozone treatment against contrast-induced nephropathy (CIN) in an experimental rat model. Methods: Thirty adult male Wistar rats were randomly distributed into five groups (n=6 for each group). Group I served as control and Group II had only contrast agent, while Group III received NAC and Group IV received intraperitoneal ozone 6 hours before and 6 hours after introduction of contrast agent. Ozone treatment was applied for 5 days after the contrast agent was introduced in Group V. After induction of CIN, groups were compared in terms of serum levels of urea, creatinine, neutrophil gelatinase associated lipocalin, protein carbonyl, total antioxidant capacity (TAC) as well as degree of renal injury at histopathologic level. Results: Groups II-V displayed more obvious histopathological alterations such as hemorrhage and renal tubular injury compared with Group I. TAC (p=0.043) and creatinine (p=0.046) levels increased significantly in Group II after the intervention. In Group III, protein carbonyl level diminished remarkably (p=0.046), while creatinine level was increased (p=0.046) following the intervention. TAC level was higher in Group IV (p=0.028) and Group V (p=0.026) following the procedure. Conclusion: The N-acetyl cysteine and ozone treatment may alleviate the biochemical and histopathological deleterious effects of contrast-induced nephropathy via enhancement of total antioxidant capacity and decreasing oxidative stress.

Stereological assessment of nephroprotective effects of Trachyspermum ammi essential oil against carbon tetrachloride-induced nephrotoxicity in mice / Evaluación estereológica de los efectos nefroprotectores del aceite esencial de Trachyspermum ammi contra la nefrotoxicidad inducida por tetracloruro de carbono en ratones

Trachyspermum ammi (T. ammi) has been used in folk medicine as anti-inflammatory, antipyretic, antibacterial, antifungal agent. The present study was conducted to investigate the protective effect of Trachyspermum ammi (T. ammi) essential oil against CC14- induced nephrotoxicity in mice. Thirty-five mice were divided into five groups as follows; positive control received olive oil 1 mL/ kg/ip, negative control received CC14 1 mg/kg/ip + 0.5 mL distilled water orally and tree treatment groups which received CC14 similar to the negative control and 200, 800 and 1600 µg/kg of T. ammi essential oil, respectively. All treatments were done twice a week (Saturday and Wednesday) for 45 days. On the last day, blood was sampled for urea and creatinine assessment and the left kidney was removed for stereological estimations. Essential oil of T. ammi at high dose significantly (p ≤ 0.05) decreased serum levels of creatinine and urea in comparison with CC14-treated group. Total volume of the kidney, cortex, proximal convoluted tubules (PC), glomerulus, vessels and interstitial tissue as well as total length of PC and vessel were significantly (p ≤ 0.05) increased following CC14 administration and were restored toward normal levels at high dose of T. ammi. Also, high dose of T. ammi improved glomerular loss significantly (p ≤ 0.05) as compared with CC14-treated group. Due to the chemical composition of T. ammi essential oil such as tymol, p-cymene, γ-terpinene which are antioxidant, it can be concluded that the essential oil of T. ammi can ameliorated renal injury induced following CC14 toxicity via its antioxidant components.

En la medicina popular se ha utilizado el aceite esencial de Trachyspermum ammi (T. ammi) como agente antiinflamatorio, antipirético, antibacteriano y anti fúngico. El presente estudio se realizó para investigar el efecto protector de Trachyspermum ammi (T. ammi) aceite esencial contra la nefrotoxicidad inducida en ratones. Treinta y cinco ratones fueron divididos en cinco grupos de la siguiente manera; el control positivo recibió 1 mL / kg / ip de aceite de oliva, el control negativo recibió 1 mg / kg / ip + 0,5 mL de agua destilada por vía oral y grupos de tratamiento arbóreo que recibieron un control similar al negativo y 200, 800 y 1600 mg / kg de T. aceite esencial de T. ammi, respectivamente. Todos los tratamientos se realizaron dos veces por semana (sábado y miércoles) durante 45 días. En el último día de tratamiento, se tomaron muestras de sangre para evaluar la urea y la creatinina, y se extrajo el riñón izquierdo para realizar estimaciones estereológicas. El aceite esencial de T. ammi a dosis altas significativamente (p ≤ 0,05) disminuyó los niveles séricos de creatinina y urea en comparación con el grupo tratado. El volumen total del riñón, la corteza, los túbulos contorneados proximales (PC), el glomérulo, los vasos y el tejido intersticial, así como la longitud total de la PC y el vaso aumentaron significativamente (p ≤ 0,05) después de la administración y se restablecieron a niveles normales con dosis altas de T. ammi. Además, una dosis alta de T. ammi mejoró significativamente la pérdida glomerular (p ≤ 0,05) en comparación con el grupo tratado. Debido a la composición química del aceite esencial de T. ammi como timol, p-cimeno, 𝛾-terpineno con propiedades antioxidantes, se puede concluir que el aceite esencial de T. ammi puede mejorar la lesión renal inducida después de la toxicidad a través de sus componentes antioxidantes.

Protective effect of quercetin on histomorphometric changes in kidney of retinoid acid-treated rat fetuses / Efecto protector de la quercetina sobre los cambios histomorfométricos en el riñón de fetos de rata tratados con ácido retinoico

SUMMARY: Retinoic acid, an active metabolite of vitamin A, plays essential signaling roles in mammalian embryogenesis. Prenatal rat fetuse exposure to retinoid induces some malformations in various organs, the most active and teratogenic metablolite is all-transretinoic acid (atRA). The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, quercetin, a naturally occurring flavonoid has excellent antioxidant properties. Therefore, the aim of this study was assess the protective effects of quercetin against atRA in fetuses of rat's kidney tissue. This study was performed on 40 pregnant rats that were divided into seven groups. Control group received normal saline and test groups received DMSO, quercetin (75 mg/kg), quercetin (200 mg/kg), atRA (25 mg/kg), atRA (25 mg/kg) plus quercetin (75 mg/kg) and atRA (25 mg/kg) plus quercetin (200 mg/kg), intraperitoneally at 8-10th days of gestation. Fetuses were collected at 20th day of gestation. Kidneys were collected and placed in 10 % buffered formalin solution. Then, kidneys were sectioned by routine method and stained by H&E and examined histologically. On histomorphomertrical examination, it was observed the priglomerular space and diameter of renal corpuscle in group which received only atRA were significantly (p≤0.05) greater than those received normal saline, dimethyl sulfoxide and quercetin, while these two indexes in group which received atRA plus quercetin significantly (p≤0.05) decreased by quercetin as dose dependent manner. Number of renal corpuscles were significantly (p≤0.05) decreased by atRA, but the quercetin could not affect the glomerular numbers. It is concluded that quercetin can protect fetuses against atRA damages and prevent their incidence probably via its antioxidant effect.

RESUMEN: El ácido retinoico, un metabolito activo de la vitamina A, desempeña un papel esencial de señalización en la embriogénesis de mamíferos. La exposición al ácido retinoico en fetos de ratas prenatales induce malformaciones en varios órganos, siendo el metabolito más activo y teratogénico el ácido transretinoico (ATRA). Los efectos teratogénicos de algunos medicamentos se pueden prevenir mediante la aplicación de medicamentos antioxidantes y la estimulación del sistema inmune materno. Además, la quercetina, un flavonoide de origen natural, tiene excelentes propiedades antioxidantes. Por lo tanto, el objetivo de este estudio fue evaluar los efectos protectores de quercetina contra ATRA en fetos de tejido de riñón de rata. Este estudio se realizó en 40 ratas preñadas que se dividieron en siete grupos. El grupo control recibió solución salina normal y los grupos de prueba recibieron DMSO, quercetina (75 mg / kg), quercetina (200 mg / kg), ATRA (25 mg / kg), ATRA (25 mg / kg) más quercetina (75 mg / kg) y ATRA (25 mg / kg) más quercetina (200 mg / kg), por vía intraperitoneal a los 8-10 días de gestación. Los fetos se recolectaron a los 20 días de gestación. Los riñones se recogieron y se colocaron en solución de formalina tamponada al 10 %. Luego, los riñones se seccionaron por método de rutina y se tiñeron con H & E y se examinaron histológicamente. En el examen histomorfométrico, se observó que el espacio periglomerular y el diámetro del corpúsculo renal en el grupo que recibió solo ATRA fueron significativamente (p≤0.05) mayores que los que recibieron solución salina normal, dimetilsulfóxido y quercetina, mientras que estos dos índices, en el grupo que recibió ATRA más quercetina, disminuyó significativamente (p≤0.05) en forma dependiente de la dosis. El número de corpúsculos renales disminuyó significativamente (p≤0.05) por el ATRA, pero la quercetina no pudo afectar el número de glomérulos. Se concluye que la quercetina puede proteger a los fetos contra daños de ATRA y prevenir su incidencia, probablemente, a través de su efecto antioxidante.

Nefropatia induzida por contraste (NIC), em pacientes da unidade de terapia intensiva oncológica, submetidos à tomografia computadorizada / Contrast-Induced Nephropathy (CIN) in patients from oncology intensive care unit, underwent CT scans

Introdução: a Nefropatia Induzida por Contraste (NIC) é atualmente uma das principais causas de insuficiência renal aguda (IRA), seja pela administração intra-arterial ou intravenosa do meio de contraste iodado (MCI). Existem ainda muitas dúvidas na literatura sobre a real condição que propicia a NIC e seus fatores predisponentes. Este estudo avalia a ocorrência da NIC em pacientes críticos oncológicos. Objetivo: avaliar a incidência de NIC na população de uma unidade de terapia intensiva oncológica. Materiais e Métodos: estudo prospectivo unicêntrico com um grupo de 79 pacientes internados na unidade de terapia intensiva (UTI) do A.C.Camargo Cancer Center, que foram submetidos ao exame de Tomografia Computadorizada (TC) utilizando uma injeção de MCI não iônico de baixa osmolaridade. A função renal foi avaliada pela dosagem sérica de Creatinina (79 pacientes) e Cistatina C (75 pacientes), antes e depois (72h) da administração do MCI. Resultado: nenhum paciente apresentou sinais clínicos de insuficiência renal após a administração do MCI. Dos 79 pacientes avaliados por dosagem sérica de Creatinina, apenas 1 (1,3%); IC (95%) = [0,03%; 6,9%] apresentou um aumento de pelo menos 0,5 mg/dl na dosagem realizada após a administração do MCI e 7 pacientes (8,9%); IC(95%) = [3,6%; 17,4%] apresentaram incremento de pelo menos 25%. Dos 75 pacientes avaliados com dosagem sérica de Cistatina C, 3 (4,0%); IC(95%) = [0,8%; 11,2%] tiveram um incremento na concentração do marcador de pelo menos 0,9 mg/dl e 17 (22,7%); IC(95%) = [13,8%; 33,8%] apresentaram incremento de pelo menos 10% na dosagem sérica da Cistatina C. Conclusão: O MCI de baixa osmolaridade é seguro para pacientes em unidade de terapia intensiva com baixas taxas de alteração nos marcadores de função renal (AU)

Introduction: Contrast-Induced Nephropathy (CIN) is currently a major cause of acute renal failure (ARF), either by intra-arterial or intravenous administration of iodinated contrast medium (ICM). There are many doubts and gaps in the literature about the real condition that favors CIN, and its predisposing factors. This study evaluates the occurrence of CIN in critically ill oncologic patients. Objective: To evaluate the incidence of CIN in the population of a cancer intensive care. Materials and Methods: Single-center prospective study with a group of 79 patients admitted to the intensive care unit (ICU) of the A C Camargo Cancer Center who underwent examination Computed tomography (CT) using an injection of iodinated contrast nonionic low osmolarity, the renal function was evaluated by serum creatinine (79 patients) and Cystatin C (75 patients), both before and after (72 hours) of the administration of MCI. Results: No patient develop clinical signs of renal insufficiency. Of the 79 patients evaluated by serum creatinine, 1 (1.3%; 95% CI = [0.03%, 6.9%]) had an increase of at least 0.5 mg/dL in the dosage performed after administration of ICM and 7 patients (8.9%; 95% CI = [3.6%, 17.4%]) showed an increase of at least 25% in serum creatinine after administration of ICM. Of the 75 evaluable patients with serum Cystatin C, 3 (4.0%; 95% CI = [0.8%- 11.2%]) had an increase of at least 0.9 mg/dL in the dosage performed after the administration of ICM and 17 (22.7%; 95% CI [13.8%, 33.8%]) showed an increase of at least 10% of the serum Cystatin after administration of ICM. Conclusion: The low osmolarity is safe for MCI patients in intensive care with low rates of change in markers of renal function (AU)

Assessment of nephrotoxicity and histopathological lesions of albino rats exposure to DD-force and baygon insecticides / Evaluación de la nefrotoxicidad y lesiones histopatológicas tras la exposición de ratas Albino a los insecticidas DD-Force y Baygon

Although studies suggest adverse effects of pesticides, human exposure to insecticides in homes is increasing and reports on their health effects are limited. The study investigated nephrotoxic effects of organo phosphate and carbamate insecticides, DD-Force and Baygon, in albino rats. Forty-five albino rats divided into groups were exposed to DD-Force (dichlorvos) or Baygon (propoxur) indoor insecticidein wooden boxes in separate exposure duration of 1, 2, 3 and 4 hours/day for 14 consecutive days. Serum and kidney tissue obtained after sacrifice were used to determine markers of renal damage and histopathological analysis, respectively. Exposure of rats to the insecticides showed duration-dependent significant increases (p<0.05) in serum levels of urea, uric acid and creatinine compared to control. However, rats exposed to DD-Force insecticide induced significantly higher levels of urea, uric acid and creatinine compared to Baygon (p<0.05). Histopathological lesions were observed in rats exposed to the insecticides, particularly in the exposure duration of 3 or 4 hours/day. These findings suggest that acute exposure to DD-Force and Baygonis nephrotoxic and may induce renal damage in rats.

Aunque los estudios sugieren efectos adversos de los pesticidas, la exposición humana a los insecticidas en los hogares está aumentando y los informes sobre sus efectos sobre la salud son limitados. Este estudio investigó los efectos nefrotóxicos de los insecticidas órgano fosfato y carbamato, DD-Force y Baygon, en ratas albinas. Cuarenta y cinco ratas albinas divididas en grupos fueron expuestas a DD-Force (diclorvos) o Baygon (propoxur) insecticidas de interior en cajas de madera en una duración de exposición separada de 1, 2, 3 y 4 horas / día durante 14 días consecutivos. Muestras séricas y de tejido renal obtenidas después del sacrificio se utilizaron para determinar los marcadores de daño renal y el análisis histopatológico, respectivamente. La exposición de las ratas a los insecticidas mostró aumentos significativos dependientes de la duración (p<0.05) en los niveles séricos de urea, ácido úrico y creatinina en comparación con el control. Sin embargo, las ratas expuestas al insecticida DD-Force indujeron niveles significativamente más altos de urea, ácido úrico y creatinina en comparación con Baygon (p<0.05). Se observaron lesiones histopatológicas en ratas expuestas a los insecticidas, particularmente en la duración de exposición de 3 o 4 horas/día. Estos hallazgos sugieren que la exposición aguda a DD-Force y Baygonis nephrotóxico y puede inducir daño renal en ratas.

Lesão renal aguda induzida por contraste: importância dos critérios diagnósticos para estabelecer a prevalência e o prognóstico na unidade de terapia intensiva / Contrast-induced acute kidney injury: the importance of diagnostic criteria for establishing prevalence and prognosis in the intensive care unit

RESUMO Objetivo: Estabelecer se há superioridade entre os critérios para predizer desfecho clínico desfavorável na lesão renal aguda e nefropatia induzidas por contraste. Métodos: Estudo retrospectivo conduzido em hospital terciário com 157 pacientes submetidos à infusão de contraste radiológico para fins propedêuticos. Resultados: Cumpriram os critérios para inclusão 147 pacientes. Aqueles que cumpriram os critérios de lesão renal aguda induzida por contraste (59) também cumpriram os critérios para nefropatia induzida por contraste (76); 44,3% dos pacientes cumpriram os critérios para o estadiamento pelo sistema KDIGO; 6,4% dos pacientes necessitaram utilizar terapia de substituição renal, e 10,7% dos pacientes morreram. Conclusão: O diagnóstico de nefropatia induzida por contraste foi o critério mais sensível para determinar a necessidade de terapia de substituição renal e óbito, enquanto o KDIGO demonstrou a maior especificidade; na população avaliada, não houve correlação entre o volume de contraste e a progressão para lesão renal induzida por contraste, nefropatia induzida por contraste, diálise de suporte ou óbito.

ABSTRACT Objective: To establish whether there is superiority between contrast-induced acute kidney injury and contrast-induced nephropathy criteria as predictors of unfavorable clinical outcomes. Methods: Retrospective study carried out in a tertiary hospital with 157 patients undergoing radiocontrast infusion for propaedeutic purposes. Results: One hundred forty patients fulfilled the inclusion criteria: patients who met the criteria for contrast-induced acute kidney injury (59) also met the criteria for contrast-induced nephropathy (76), 44.3% met the criteria for KDIGO staging, 6.4% of the patients required renal replacement therapy, and 10.7% died. Conclusion: The diagnosis of contrast-induced nephropathy was the most sensitive criterion for renal replacement therapy and death, whereas KDIGO showed the highest specificity; there was no correlation between contrast volume and progression to contrast-induced acute kidney injury, contrast-induced nephropathy, support dialysis or death in the assessed population.

Impact of gender in early structural changes of contrast induced nephropathy in rats / Impacto do gênero em alterações estruturais precoces da nefropatia induzida por contraste em ratos

Abstract Introduction: Contrast-induced nephropathy (CIN) is a major iatrogenic cause of acute kidney injury. Experimental studies have shown that intravascular injection causes intense vacuolization of the contrast agent in the proximal renal tubules cells, preceding the increase in serum creatinine, and that the female may be at a higher risk for CIN. Objective: To study the early kidney histomorphometric changes in contrast-induced nephropathy according to the gender. Methods: Twenty previously uninephrectomized Wistar rats were divided into 4 groups (n = 5): control males; control females; contrast exposed males; and contrast exposed females. The animals were sacrificed immediately after contrast administration and kidney tissue samples were collected for histomorphometric analysis. The research project was approved by the Research Ethics Committee of the School of Medicine of Universidade Federal Fluminense. Results: There was a more intense presence of microvacuoles in proximal tubules in the rats exposed to contrast than in the control groups. Such proximal tubular vacuolation was more intensive in the female rats (p = 0.001). Conclusion: Proximal tubular vacuolation is a very early change in CIN and is more intensive in female than in male rats.

Resumo Introdução: A nefropatia induzida por contraste (NIC) é uma das principais causas iatrogênicas de lesão renal aguda. Estudos experimentais têm demonstrado que a injeção intravascular do agente de contraste provoca vacuolização intensa nas células dos túbulos renais proximais, que precede o aumento da creatinina sérica, e que a fêmea podem estar em maior risco de CIN. Objetivo: Estudar as primeiras mudanças histomorfométricas renais na nefropatia induzida por contraste de acordo com o gênero. Métodos: Vinte ratos Wistar anteriormente uninefrectomizados foram divididos em 4 grupos (n = 5): machos de controle; fêmeas de controle; machos expostos ao contraste e fêmeas expostas ao contraste. Os animais foram sacrificados imediatamente após a administração de contraste e amostras de tecido de rim foram coletadas para análise histomorfométrica. O projeto de pesquisa foi aprovado pelo Comitê de Ética em Pesquisa da Faculdade de Medicina da Universidade Federal Fluminense. Resultados: Houve presença mais intensa de microvacuolização em túbulos proximais nos ratos expostos ao contraste do que nos grupos de controle. Tal vacuolização tubular proximal foi mais intensa nos ratos do sexo feminino p = 0,001). Conclusão: Vacuolização do tpubulo proximal é uma mudança precoce na CIN e é mais intensa em ratos fêmeas do que em ratos machos.

Tribulus terrestris hydroalcoholic extract effect on cisplatin-induced apoptosis in mice kidney / Efecto del extracto hidroalcohólico de Tribulus terrestris sobre la apoptosis Inducida por cisplatino en el riñón de ratones

Cisplatin (EBEWE Pharma, Unterach, Austria) is an anti-cancer drug used in chemotherapy. One of the limiting major side effects of cisplatin is nephrotoxicity. Tribulus terrestris (TT) has been used as an synthetic or herbal protective agents for kidney disorders. The present study amid to investigate the Tribulus terrestris Hydroalcoholic extract effect on cisplatin-induced apoptosis in mice kidney. Male adult mice (n= 30) were divided into control group and 4 experimental groups (n= 6). Control group received saline, the first experimental group received cisplatin (5.5 mg/kg) and other three experimental groups received cisplatin (5.5 mg/kg) and different doses of hydroalcoholic extact of TT (100, 300 and 500 mg/kg i.p) respectively. The kidneys were removed after 4 days of injections, and TUNEL assay on mice's kidneys were performed. Weights of body and kidneys and apoptotic index were assessed. Data analysis was performed using one-way ANOVA followed by Tukey's post hoc test. The results showed that cisplatin lead to a reduction in the weight of body and kidney (P <0.01), and increased apoptotic index significantly compared to the control group (P <0.001), while in treated groups with TT, the weights of body and kidney were significantly higher compared with cisplatin group, but apoptotic index did not show significant differences. These parameters reached normal range after administration of fruit extracts of TT for 4 days. The study demonstrates that extract of TT could have protective effect on cisplatin- induced apoptosis of kidney. This may be related to the presence of antioxidant components acting via a multitude of central and peripheral mechanisms.

El cisplatino (EBEWE Pharma, Unterach, Austria) es un medicamento contra el cáncer utilizado en quimioterapia. Uno de los principales efectos secundarios limitantes del cisplatino es la nefrotoxicidad. Tribulus terrestris (TT) ha sido utilizado como agente protector sintético o herbal para los trastornos renales. El objetivo fue investigar el efecto del extracto hidroalcohólico de TT sobre la apoptosis inducida por cisplatino en el riñón de ratones. Se utilizaron ratones adultos machos (n= 30), que fueron divididos en 4 grupos, un control y tres grupos experimentales (n= 6). El grupo control recibió solución salina; el primer grupo experimental recibió cisplatino (5,5 mg/kg) y los otros tres grupos experimentales recibieron cisplatino (5,5 mg/kg) con diferentes dosis de extracto hidroalcohólico de TT (100, 300 y 500 mg/kg vía ip) respectivamente. Los riñones fueron retirados después de 4 días de aplicadas las inyecciones, y se realizó el ensayo TUNEL en los riñones. Se evaluó el peso corporal de los ratones, el peso de los riñones y el índice de apoptosis. El análisis de datos se realizó mediante ANOVA de un factor seguido por la prueba post hoc de Tukey. Los resultados mostraron que el cisplatino con plomo provocó una reducción en el peso corporal y el riñón (P <0,01) y un aumento significativo del índice de apoptosis en comparación con el grupo control (P <0,001), mientras que en los grupos tratados con TT, los pesos corporales y de los riñones fueron significativamente mayores en comparación con el grupo de cisplatino, pero el índice de apoptosis no mostró diferencias significativas. Estos parámetros alcanzaron niveles normales después de la administración de extracto de TT durante 4 días. El estudio demuestra que el extracto de TT podría tener un efecto protector sobre la apoptosis inducida por cisplatino en el riñón, que podría estar relacionado con la presencia de componentes antioxidantes que actúan a través de múltiples mecanismos centrales y periféricos.

Proteína C-Reativa Ultrassensível em Pacientes Submetidos a Exames Contrastados / High-Sensitivity C-Reactive Protein in Patients Undergoing Contrast Studies

A utilização de agentes iodados em exames radiológicos pode causar nefropatia induzida porcontraste (NIC) na presença de fatores de risco clássicos, como doença renal prévia e diabetes. Recentemente,níveis séricos elevados de proteína C-reativa ultrassensível (PCR-us) têm sido descritos como indicadores de maior risco de NIC. Independente da ocorrência de NIC, a PCR-us pode elevar-se após exames contrastados.Objetivo: Investigar o comportamento da PCR-us em pacientes submetidos à administração parenteral de agentede contraste iodado. Métodos: Estudo observacional, transversal, prospectivo, realizado no Hospital Universitário Antônio Pedro, de 2007 a 2014, envolvendo 51 pacientes, 30 homens e 21 mulheres, média de idade 60,19±20,0 anos, submetidos aexames com contraste de baixa osmolalidade (Iopamidol 612 mg/mL).Resultados: NIC ocorreu em 15 pacientes (29,4%). Não houve correlação entre a PCR-us aumentada e a ocorrência de NIC. O aumento percentual da PCR-us foi significativamente maior entre os pacientes submetidos ao cateterismocardíaco (p=0,0044). O aumento médio da PCR-us nos pacientes submetidos ao cateterismo cardíaco e naquelessubmetidos à administração do contraste iodado por veia periférica foi 100,3% e 13,8%, respectivamente.Conclusão: Os achados sugerem que o aumento da PCR-us após cateterismo cardíaco não pode ser atribuído aoagente de contraste iodado...

Background: The use of iodinated agents in radiological studies can cause contrast-induced nephropathy (CIN) in the presence of classic risk factors such as previous renal disease and diabetes. High serum levels of high-sensitivity C-reactive protein (CRP) have been described as indicators of increased risk of CIN. Regardless of the occurrence of CIN, hs-CRP may rise after contrast studies. Objective: To investigate the behavior of hs-CRP in patients undergoing parenteral administration of iodinated contrast agent. Methods: Observational cross-sectional prospective study held at Hospital Universitário Antônio Pedro from 2007 to 2014 involving 51 patients, 30 men and 21 women, mean age 60.19±20.0, undergoing tests with low-osmolality contrast (Iopamidol 612mg/ml).Results: CIN occurred in 15 patients (29.4%). There was no correlation between increased hs-CRP and occurrence of CIN. The percentage increase in hs-CRP was significantly higher among patients undergoing cardiac catheterization (p=0.0044). The mean increase in hs-CRP in patients undergoing cardiac catheterization and in those submitted to administration of iodinated contrast by peripheral vein was 100.3% and 13.8%, respectively.Conclusion: The findings suggest that increased hs-CRP after cardiac catheterization cannot be attributed to iodinated contrast agente...