ABSTRACT
Abstract Introduction: Glyphosate is the most widely used herbicide worldwide and in Brazil. There is currently increasing concern about the effects of glyphosate on human health. The Brazilian Institute for Consumer Protection showed data on the presence of glyphosate in some of Brazil's most consumed ultra-processed products. Currently, regulations on the upper limit for these residues in ultra-processed foods have yet to be established by the National Health Surveillance, and ultra-processed food consumption is independently associated with an increased risk of incident chronic kidney disease. Methods: Since an unbalanced diet can interfere with kidney function, this study aims to investigate the effect of daily intake of 5 mg/kg bw glyphosate in conjunction with a balanced diet and the possible impact on renal function in rats. Kidney function, kidney weight, markers of renal injury, and oxidative stress were evaluated. Results: There was a decrease in kidney weight. The main histopathological alterations in renal tissues were vacuolation in the initial stage and upregulation of the kidney injury marker KIM-1. Renal injury is associated with increased production of reactive oxygen species in mitochondria. Conclusion: This study showed changes in the kidney of rats exposed to a balanced diet with glyphosate, suggesting a potential risk to human kidney. Presumably, ultra-processed food that contain glyphosate can potentiate this risk. The relevance of these results lies in drawing attention to the need to regulate glyphosate concentration in ultra-processed foods in the future.
RESUMO Introdução: O glifosato é o herbicida mais utilizado no mundo e no Brasil. Atualmente, há uma preocupação crescente com os efeitos do glifosato na saúde humana. O Instituto Brasileiro de Defesa do Consumidor apresentou dados sobre a presença de glifosato em alguns dos produtos ultraprocessados mais consumidos no Brasil. Atualmente, as regulamentações sobre o limite máximo desses resíduos em alimentos ultraprocessados ainda não foram estabelecidas pela Vigilância Sanitária Nacional, e o consumo de alimentos ultraprocessados está independentemente associado a um risco maior de doença renal crônica incidente. Métodos: Como uma dieta desbalanceada pode interferir na função renal, este estudo tem como objetivo investigar o efeito da ingestão diária de 5 mg/kg pc de glifosato em conjunto com uma dieta equilibrada e o possível impacto na função renal em ratos. Foram avaliados função renal, peso dos rins, marcadores de lesão renal e estresse oxidativo. Resultados: Houve redução no peso dos rins. As principais alterações histopatológicas nos tecidos renais foram vacuolização no estágio inicial e regulação positiva do marcador de lesão renal KIM-1. A lesão renal está associada à produção aumentada de espécies reativas de oxigênio nas mitocôndrias. Conclusão: Esse estudo mostrou alterações nos rins de ratos expostos a uma dieta balanceada com glifosato, sugerindo um risco potencial ao rim humano. Presumivelmente, alimentos ultraprocessados que contenham glifosato podem potencializar esse risco. A relevância desses resultados está no fato de chamar a atenção para a necessidade de regulamentar a concentração de glifosato em alimentos ultraprocessados no futuro.
ABSTRACT
SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.
Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.
ABSTRACT
SUMMARY: The toxic effects of acetaminophen appear primarily in the liver and kidney. The protective effect of blue green alga Arthrospira platensis on hepato-renal toxicity caused by acetaminophen was evaluated in male rats. The obtained results showed that subcutaneous injection of acetaminophen at a dose 120 &240 սl acetaminophen/kg by weight resulted in an observed elevation in the enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Alkaline phosphatase (ALP), serum total lipids, total cholesterol, creatinine, total bilirubin, urea, nitric oxide (NO), L- malondialdehyde (MDA) and interleukins (IL-2 &IL-6). However, there is a decrease in the serum total protein, albumin and loss in antioxidant enzyme activities in liver including; superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH). This effect was found to be dose and time dependent. In spite of, pre- oral administration of Arthrospira platensis 1000 mg/kg .b. wt. prior acetaminophen injection succeeded to modulate the effect of the observed abnormalities caused by acetaminophen. Moreover, there were no remarkable changes in serum biomarkers of rats received Arthrospira platensis only at a dose of 1000 mg/kg by weight (group 2). The histopathological findings confirm the biochemical results that indicates the safety use of Arthrospira platensis at the selected dose in this study. Therefore, the present results clarified the protective effect of blue green alga Arthrospira platensis on oxidative stress, hepatic and nephrotoxicity induced by acetaminophen in male Wister rats.
Los efectos tóxicos del paracetamol aparecen principalmente en el hígado y el riñón. Se evaluó en ratas macho Wistar el efecto protector del alga verde azulada Arthrospira platensis sobre la toxicidad hepatorrenal causada por paracetamol. Los resultados obtenidos mostraron que la inyección subcutánea de paracetamol a dosis de 120 y 240 µl de paracetamol/kg, resultó en una elevación en las actividades enzimáticas de la aspartato aminotransferasa (AST), alanina aminotransferasa (ALT) y fosfatasa alcalina (ALP), lípidos séricos totales, colesterol total, creatinina, bilirrubina total, urea, óxido nítrico (NO), L- malondialdehído (MDA) e interleucinas (IL-2 e IL-6). Sin embargo, hay una disminución en la proteína sérica total, albúmina y pérdida en las actividades de las enzimas antioxidantes en el hígado, incluyendo; superóxido dismutasa (SOD), catalasa (CAT) y glutatión reductasa (GSH). Se encontró que este efecto era dependiente de la dosis y el tiempo. A pesar de la administración preoral de Arthrospira platensis 1000 mg/kg, la inyección previa de acetaminofeno logró modular el efecto de las anormalidades observadas causadas por el acetaminofeno. Además, no hubo cambios notables en los biomarcadores séricos de ratas que recibieron Arthrospira platensis solo a una dosis de 1000 mg/kg (Grupo 2). Los hallazgos histopatológicos confirman los resultados bioquímicos que indican la seguridad del uso de Arthrospira platensis a la dosis seleccionada en este estudio. Por lo tanto, los presentes resultados aclararon el efecto protector del alga verde azulada Arthrospira platensis sobre el estrés oxidativo, la toxicidad hepática y la nefrotoxicidad inducida por paracetamol en ratas Wistar macho.
Subject(s)
Animals , Male , Rats , Plant Preparations/administration & dosage , Spirulina , Kidney/drug effects , Liver/drug effects , Acetaminophen/toxicity , Aspartate Aminotransferases/analysis , Superoxide Dismutase , Lipid Peroxidation , Interleukins , Rats, Wistar , Alanine Transaminase/analysis , Alkaline Phosphatase/analysisABSTRACT
SUMMARY: To investigate if the administration of boric acid (BA) would exert any protective effect against possible nephrotoxicity and hepatotoxicity induced by the exposure to acrylamide (ACR) in rats. In our study, we used a total of 28 rats that were divided into four equal groups. Group 1: the control group which was not treated with any procedure. Group 2: the ACR group that was administered ACR 50 mg/kg/day via intraperitoneal (i.p) route for 14 days. Group 3: the BA group that was administered BA 200 mg/kg/ day via gavage via peroral (p.o) route for 14 days. Group 4: the ACR+BA group that was administered BA simultaneously with ACR. Total antioxidant and oxidant (TAS/TOS) capacities were measured in all groups at the end of the experiment. In addition, the specimens obtained were evaluated with histopathological examination. Studies showed that the ACR and ACr+BA groups were not significantly different in terms of hepatic TAS level while the TOS level was higher in the ACR group than the ACR+BA group. The groups did not show any significant difference regarding renal TAS and TOS levels. In the histopathological examination of the hepatic tissue, the histopathological injury score of the ACR group was significantly higher than those of the other groups whereas it was significantly lower in the ACR+BA group than the ACR group. Our study concluded that Boric acid had a protective effect against acrylamide- induced hepatotoxicity, but not against nephrotoxicity.
El objetivo de este estudio fue investigar si la administración de ácido bórico (BA) ejercería algún efecto protector frente a la posible nefrotoxicidad y hepatotoxicidad inducida por la exposición a acrilamida (ACR) en ratas. En nuestro estudio, utilizamos un total de 28 ratas que se dividieron en cuatro grupos iguales. Grupo 1: grupo control que no fue tratado. Grupo 2: grupo ACR al que se le administró ACR 50 mg/kg/día por vía intraperitoneal (i.p) durante 14 días. Grupo 3: grupo BA al que se le administró BA 200 mg/kg/día por sonda por vía peroral (p.o) durante 14 días. Grupo 4: grupo ACR+BA al que se administró BA simultáneamente con ACR. Las capacidades antioxidantes y oxidantes totales (TAS/TOS) se midieron en todos los grupos al final del experimento. Además, los especímenes obtenidos fueron evaluados con examen histopatológico. Los estudios demostraron que los grupos ACR y ACr+BA no fueron significativamente diferentes en términos del nivel hepático de TAS, mientras que el nivel de TOS fue mayor en el grupo ACR que en el grupo ACR+BA. Los grupos no mostraron ninguna diferencia significativa con respecto a los niveles renales de TAS y TOS. En el examen histopatológico del tejido hepático, la puntuación de lesión histopatológica del grupo ACR fue significativamente mayor que la de los otros grupos, mientras que fue significativamente menor en el grupo ACR+BA que en el grupo ACR. Nuestro estudio concluyó que el ácido bórico tiene un efecto protector contra la hepatotoxicidad inducida por acrilamida, pero no contra la nefrotoxicidad.
Subject(s)
Animals , Rats , Boric Acids/administration & dosage , Acrylamide/toxicity , Chemical and Drug Induced Liver Injury/prevention & control , Acute Kidney Injury/prevention & control , Biochemistry , Protective Agents/administration & dosage , Chemical and Drug Induced Liver Injury/pathology , Acute Kidney Injury/chemically induced , Acute Kidney Injury/pathology , Kidney/drug effects , Kidney/physiopathology , Liver/drug effects , Liver/physiopathologyABSTRACT
Aim To investigate the mechanism of Sophorae tonkinensis radix et rhizome (ST) induced nephrotoxicity based on network toxicology and experimental verification. Methods Through network toxicology the target of toxic components of ST was predicted, nephrotoxicity-related target genes were located, the intersection of targets was taken, the STRING platform was imported to map the target protein interactions, MetaScape database was used for GO and KEGG analysis, BioGPS database for screening the key expressed genes in rat nephrotoxicity and the component-target-pathway network was constructed. The mechanism of ST induced nephrotoxicity was verified through animal experiments, and qRT-PCR was applied to detect mRNA expression level of key genes in kidney tissue. Results Twenty toxic components of ST were screened from network toxicology, mainly including matrine, sophoridine, maackiain. A total of 135 targets were involved, and HSP90AA1, SRC, MAPK1, MAPK3, AKT1 were the main targets. A total of 169 related signaling pathways were yielded by KEGG analysis, and the mechanism of nephrotoxicity might be related to cancer pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway. PPARA, RAF1, MAP2K1, SRC, AKT1 and MAPK3 were screened from BioGPS database. The results of animal experiments showed that BUN and SCr level increased (P <0. 01) in rats with high-dose group, and the kidney tissue was significantly damaged. qRT-PCR results indicated that the expression of PPARA, RAF1, MAP2K1, MAPK3 mRNA increased, the expression of AKT1 mRNA decreased in the high-dose group of ST (P <0. 05). Conclusions The mechanism of Sophorae tonkinensis radix et rhizome induced nephrotoxicity is found to be related to the combined action of multiple components, multiple targets and multiple pathways, which also provides a theoretical basis for the in-depth exploration of the toxicology.
ABSTRACT
OBJECTIVE@#To study the toxic effects of short-term exposure to gossypol on the testis and kidney in mice and whether these effects are reversible.@*METHODS@#Twenty 7 to 8-week-old male mice were randomized into blank control group, solvent control group, gossypol treatment group and drug withdrawal group. In the former 3 groups, the mice were subjected to daily intragastric administration of 0.3 mL of purified water, 1% sodium carboxymethylcellulose solution, and 30 mg/mL gossypol solution for 14 days, respectively; In the drug withdrawal group, the mice were treated with gossypol solution in the same manner for 14 days followed by treatment with purified water for another 14 days. After the last administration, the mice were euthanized and tissue samples were collected. The testicular tissue was weighed and observed microscopically with HE and PAS staining; the kidney tissue was stained with HE and examined for mitochondrial ATPase activity.@*RESULTS@#Compared with those in the control group, the mice with gossypol exposure showed reduced testicular seminiferous epithelial cells with rounded seminiferous tubules, enlarged space between the seminiferous tubules, interstitium atrophy of the testis, and incomplete differentiation of the spermatogonia. The gossypol-treated mice also presented with complete, non-elongated spermatids, a large number of cells in the state of round spermatids, and negativity for acrosome PAS reaction; diffuse renal mesangial cell hyperplasia, increased mesangial matrix, and adhesion of the mesangium to the wall of the renal capsule were observed, with significantly shrinkage or even absence of the lumens of the renal capsules and reduced kidney mitochondrial ATPase activity. Compared with the gossypol-treated mice, the mice in the drug withdrawal group showed obvious recovery of morphologies of the testis and the kidney, acrosome PAS reaction and mitochondrial ATPase activity.@*CONCLUSIONS@#Shortterm treatment with gossypol can cause reproductive toxicity and nephrotoxicity in mice, but these toxic effects can be reversed after drug withdrawal.
Subject(s)
Mice , Male , Animals , Gossypol/toxicity , Testis , Seminiferous Tubules , Spermatids , Spermatogenesis , Adenosine Triphosphatases/pharmacologyABSTRACT
Bisphenol A (BPA) is widely used to produce epoxy resin and polycarbonate plastic products. In severe cases, these plastics may release BPA, which then infiltrates into the environment. Various concentrations of BPA have been found in most biological fluid. Its presence has been well shown to be closely related to many chronic diseases, including chronic kidney disease (CKD). However, little is known regarding the adverse effects of BPA exposure and its succedent cellular events on CKD. Hence, in the current in vivo study, we aimed to assess the effects of chronic exposure to BPA on animal nephrotoxicity through investigating oxidative stress and apoptosis. Upon exposure to BPA at 0.01, 0.1, and 1 mg/L via drinking water for four weeks, the mated and pregnant females were continuously exposed to BPA until weaning. Subsequently, three weeks old F1-male neonates were also orally challenged with the same three doses of BPA for ten weeks. The results showed that the kidneys of 0.1 and 1 mg/L BPA-treated mice were seriously damaged; the contents of serum renal function indexes and lipid peroxidation products were significantly increased, including urea nitrogen, creatinine, uric acid, and thiobarbituric acid reactive substances; the morphological structure of mouse kidneys was impaired; the expressions of antioxidant-related genes at mRNA and protein levels from mouse kidneys were markedly diminished, including glutathione-S-transferase, superoxide dismutase, and catalase; the expressions of genes and proteins related to apoptosis index (ratio of Bax/Bcl-1 and Caspase-3) were significantly enhanced. The data manifested that cumulative oxidative stress and apoptosis might play an essential role in the animal nephrotoxicity induced by chronic exposure to BPA.
Subject(s)
Female , Male , Mice , Animals , Oxidative Stress , Antioxidants , Apoptosis , Renal Insufficiency, ChronicABSTRACT
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.
Subject(s)
Male , Animals , Rats , Kidney Diseases/chemically induced , Kidney/drug effects , Thimerosal/adverse effects , Thimerosal/toxicity , Rats, WistarABSTRACT
Abstract 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-B), tumor necrosis factor- (TNF-), Interleukin-1 (IL-1), 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.
Resumo 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-B), fator de necrose tumoral- (TNF-), interleucina-1 (IL-1), 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.
ABSTRACT
OBJECTIVE To evaluate the incidence of nephrotoxicity in patients with drug-resistant Gram-negative bacterial infections after the use of polymyxin， and to provide evidence-based reference for clinical rational drug use. METHODS PubMed， Embase， Web of Science， the Cochrane Library， Wanfang database， CNKI， VIP and SinoMed were searched to collect randomized controlled trials （RCTs） or cohort studies about the polymyxin （trial group） versus other antibiotics （control group） or polymyxin B （trial group） versus polymyxin E （control group）. After literature screening， data extraction and quality evaluation， RevMan 5.4.1 software was used for meta-analysis. RESULTS A total of 37 studies were included， including 4 RCTs and 33 cohort studies， with a total of 5 871 patients. The meta-analysis results showed that in RCT [RR＝2.64，95%CI （1.43，4.87），P＝0.002] and in cohort studies [RR＝1.59， 95%CI （1.27， 1.98）， P＜0.000 1]， the incidence of nephrotoxicity in the trial group was significantly higher than control group. The results of the subgroup analysis of cohort studies showed that the incidence of nephrotoxicity in the trial group （receiving polymyxin） was significantly higher than control group （receiving new β-lactam and β-lactamase inhibitors and tigecycline）； when Kidney Disease Improving Global Outcomes （KDIGO）， renal replacement therapy or 0.5 times increase in serum creatinine were used as the standard of nephrotoxicity， the incidence of nephrotoxicity in the trial group was significantly higher than the control group （P＜0.05）. The incidence of nephrotoxicity in patients receiving polymyxin E was significantly higher than those using polymyxin B [RR＝0.57， 95%CI （0.39，0.84）， P＝0.005]. CONCLUSIONS In the treatment of drug-resistant Gram-negative bacteria infections， the incidence of nephrotoxicity caused by polymyxin is relatively high. The TYU108F）； incidence of nephrotoxicity caused by polymyxin E is higher than polymyxin B.
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Introducción: múltiples agentes quimioterapéuticos que se usan comúnmente pueden causar síndrome de Fanconi (SF) completo o parcial. El SF es una tubulopatía proximal que produce alteraciones electrolíticas y ácido-básicas, donde se evidencia pérdida de glucosa, aminoácidos, calcio, fósforo, potasio, ácido úrico y se produce acidosis metabólica por pérdida de bicarbonato. El SF usualmente no es reportado y muchas veces no se realiza el diagnóstico. Objetivo: resaltar la importancia del monitoreo urinario y sérico en pacientes que estén sometidos a quimioterapia, así como describir la literatura reciente acerca de la asociación entre agentes quimioterapéuticos y síndrome de Fanconi parcial o completo. Presentación de los casos: se presenta una serie de casos de pacientes pediátricos oncológicos con función renal preservada, donde se produjeron diferentes manifestaciones de nefrotoxicidad tubular proximal secundaria a agentes quimioterapéuticos como antimetabolitos, agentes alquilantes y antraciclinas. Discusión y conclusión: el espectro del SF puede ir de una tubulopatía proximal generalizada o completa a alteraciones parciales en la reabsorción de electrolitos. Se debe reconocer la importancia del monitoreo sérico y urinario en pacientes con lesiones tumorales que van a ser sometidos a quimioterapias con agentes potencialmente nefrotóxicos; asimismo, tener en cuenta la dosis, la frecuencia y la combinación de agentes quimioterapéuticos, con el fin de prevenir y tratar complicaciones de toxicidad renal, incluyendo SF completo o parcial.
Introduction: Several commonly used chemotherapeutic agents can cause complete or partial Fanconi syndrome (FS). FS is a proximal tubulopathy that produces electrolyte and acid base disorders where there is loss of glucose, amino acids, calcium, phosphorus, potassium, uric acid and metabolic acidosis occurs due to loss of bicarbonate. FS is not usually reported, and the diagnosis is often misled. Purpose: To highlight the importance of urinary and serum monitoring in patients undergoing chemotherapy, as well as describe the recent literature about the association between chemotherapeutic agents and partial or complete Fanconi syndrome. Case presentation: A series of cases of pediatric oncology patients with preserved renal function is presented in which different manifestations of proximal tubular nephrotoxicity occurred secondary to chemotherapeutic agents such as antimetabolites, alkylating agents, and anthracyclines. Discussion and conclusion: The spectrum of FS can range from a generalized or complete proximal tubulopathy to partial alterations in electrolyte reabsorption. The importance of serum and urinary monitoring should be recognized in patients with tumor lesions who will undergo chemotherapies with potentially nephrotoxic agents; the dosage, frequency and combination of chemotherapeutic agents should be taken into account, in order to prevent and treat the complications of renal toxicity including complete or partial SF.
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Abemaciclib (ABE) has been reported to cause gastrointestinal toxicity. Therefore, it is important to investigate the question of whether abemaciclib administration causes nephrotoxicity in the gastrointestinal tract, and if so, what pathophysiological pathways it follows. In this study, the relationship between ABE administration and nephrotoxicity and the protective effect of Curcumin (CMN) was investigated. Forty female rats were equally divided into the sham, dimethyl sulfoxide (DMSO), CMN, abemaciclib and ABE+CMN groups. Aquaporin (AQP) 1-7, TNF-?, IL-1?, intercellular adhesion molecule (ICAM)-1, IL-10 and IL-37 levels in serum and kidney tissue homogenates were measured by ELISA. In addition, Urea and Creatinine were measured in serum samples. Furthermore, histopathological examination was performed in kidney tissues and Bax, Caspase-3 and Bcl-2 expression levels were determined immunohistochemically. The levels of AQP1-7 and IL-10 in the ABE group were partially lower than in the other groups, while the ratio of TNF?, IL-1?, MDA, caspase-3 and Bax/Bcl2 were high. In addition, kidney tissue was examined histopathologically. However, AQP1 and 7 levels in the ABE+CMN group were higher than in the ABE group, while TNF-?, IL-1?, MDA, Caspase-3 levels and Bax/Bcl2 ratio were low. In addition, the poor histopathological changes in the ABE group were largely restored in the ABE+CMN. The data presented that ABE in rats can adversely affect functions and histology of kidneys through the increase in oxidative stress, pro-inflammatory cytokines and apoptosis, but CMN therapy may be protective against the nephrotoxic effects of ABE
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Objectives: To determine the incidence and frequency of adverse drug reactions (ADRs) to find out factors, if any contributing to the same, while also exploring the use of amphotericin B deoxycholate as a cheaper and safe alternative to liposomal amphotericin B. Materials and Methods: It was a cross-sectional observational study, with a study population of 50 conducted over three months after ethics approval. All adult patients admitted to a tertiary care center, in a metropolitan city of Maharashtra, diagnosed with Rhino-orbito-cerebral mucormycosis, with a history of previous COVID-19 infection and receiving antifungals for the treatment of the same were included in the study. Central Drugs Standard Control Organization (CDSCO) ADR reporting forms were used to collect data. Results: Electrolyte disturbances mainly hypokalemia were the most frequently encountered ADR with both Amphotericin formulations (39/50; 20.31%) followed by pain at the injection site (33/50; 17.19%). Nephrotoxicity occurred slightly more frequently with Amphotericin B Deoxycholate (19/29; 65%), compared to Liposomal Amphotericin B (11/19; 57%), while Posaconazole was mainly associated with gastrointestinal (GI) disturbances and hepatotoxicity. Conclusion: Amphotericin B Deoxycholate was associated most with ADRs, hypokalemia, and pain at the injection site being the most frequent. However, concerning nephrotoxicity, both Amphotericin formulations showed only a modest difference. Posaconazole was associated with the least number of ADRs and had a favorable safety profile.
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Nephrotoxicity, the prevalence and incidence of which is increasing day by day, is affecting very badly the quality of life of the sufferers in addition to the impalement of physical, mental, social and economical damages. The fact that the mortality rate of hospitalized patients with acute kidney injury over the last 40–50 years is almost constant and is not improving itself iterates its graveness. Treatment/management of acute kidney injury is primarily supportive, with the goals of preventing further damage and promoting recovery of renal function. It may include discontinuation, dose adjustment or monitoring of the medications prescribed. There are only few drugs like melatonin and lithium which are supposed to be having the potential of mitigation of drug-induced nephrotoxicity. If metabolic derangements from acute kidney injury do not respond to conservative treatment, either dialysis or renal replacement therapy is the only option to ensure the maintenance of homeostasis. But neither hemodialysis nor renal transplantation, which themselves bring about a lot of personal and familial difficulties, is free from side/adverse effects. Ayurveda, the ancient healing science, describes a lot of measures for the prevention and management of diseases in a great detail. Although nephrotoxicity seems to be a new entity, it can be very well prevented and managed with the adoption of Ayurveda in a cost effective and safe way. This article presents the nehroprotective effect of Ayurvedic advocacy and that of Ayurvedic plants evident by experiments in animal model.
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Gentamicin induced acute nephrotoxicity (GIAN) is considered as one of the important causes of acute renal failure. In recent years' great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of GIAN. Hence, the current study was designed to investigate the effect of green coffee bean extract (GCBE) on GIAN in rats. Results of the present study showed that rat groups that received oral GCBE for 7 days after induction of GIAN(by a daily intraperitoneal injection of gentamicin for 7days), reported a significant improvement in renal functions tests when compared to the GIAN model groups. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE-treated groups when compared to GIAN model group. These results indicate that GCBE has a potential role in ameliorating renal damage involved in GIAN.
La nefrotoxicidad aguda inducida por gentamicina (GIAN) se considera una de las causas importantes de insuficiencia renal aguda. En los últimos años, el gran esfuerzo se ha centrado en la introducción de la medicina herbal como un nuevo agente terapéutico para la prevención de GIAN. Por lo tanto, el estudio actual fue diseñado para investigar el efecto del extracto de grano de café verde (GCBE) sobre la GIAN en ratas. Los resultados del presente estudio mostraron que los grupos de ratas que recibieron GCBE oral durante 7 días después de la inducción de GIAN (mediante una inyección intraperitoneal diaria de gentamicina durante 7 días), informaron una mejora significativa en las pruebas de función renal en comparación con los grupos del modelo GIAN. Además, hubo una mejora significativa en los marcadores de estrés oxidativo renal (malondialdehído renal, superóxido dismutasa renal) y cambios histopatológicos renales en los grupos tratados con GCBE en comparación con el grupo del modelo GIAN. Estos resultados indican que GCBE tiene un papel potencial en la mejora del daño renal involucrado en GIAN.
Subject(s)
Animals , Male , Rats , Plant Extracts/administration & dosage , Gentamicins/toxicity , Coffea/chemistry , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Antioxidants/administration & dosage , Superoxide Dismutase/analysis , Plant Extracts/pharmacology , Rats, Wistar , Coffee , Oxidative Stress/drug effects , Kidney/drug effects , Kidney/pathology , Kidney Function Tests , Malondialdehyde/analysis , Antioxidants/pharmacologyABSTRACT
Objectives: Cadmium is an essential industrial metal and acts as an environmental toxicant that is a major cause of kidney diseases. Hence, we aimed to evaluate the possible nephroprotective effects of zingerone (ZGO), a major flavonoid constituent in ginger (Zingiber officinale) dry roots, against cadmium-induced nephrotoxicity in rats. Methods: In this study, Wistar albino rats [ACUC: HU2020/Z/FMS0120-01] were allocated randomly to 4 groups with seven animals in each group. The control group which received physiological saline; cadmium chloride (CdCl2) treatment group which received CdCl2 at a dose of 6.5 mg/kg intraperitoneally (i.p.) for 7 consecutive days; zingerone treatment group which received 25 mg/kg of zingerone orally for 7 consecutive days and CdCl2(6.5 mg/kg; i.p.)+ZGO (25 mg/kg; p.o.) treatment group which received CdCl2 and ZGO for 7 consecutive days. Results: Co-administration of ZGO along with CdCl2 resulted in a significant reduction in creatinine and urea levels of serum. Additionally, ZGO significantly diminished the tissue levels of Cd concentration, lipid peroxidation, and nitric oxide and significantly recovered the enzymatic and nonenzymatic antioxidant molecules, namely glutathione, total superoxide dismutase, catalase, and glutathione recycling enzymes peroxidase and reductase, in kidney tissue. Furthermore, ZGO treatment prevented the inflammation produced by CdCl2 by restraining the elevation in the level of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin1beta). Moreover, ZGO improved histopathological alternations in the kidney by preventing apoptosis cascade in kidney tissue by stimulating Bcl-2 and suppressing Bax and caspase-3. Conclusions: Our findings suggest that ZGO has nephroprotective activity in cadmium-induced nephrotoxicity mostly via modulating of oxidant/antioxidant balance, inflammatory response, and apoptosis.
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Aim Arsenic trioxide (ATO, As203 ) can effectively treat acute promyelocyte leukemia (APL) and other malignant tumors.However.ATO has been found to have nephrotoxic effects during the treatment process, which limits the clinical application of ATO.Studies have shown that the use of ATO can interfere with the body's oxidation, causing to oxidative stress, damage DNA repair pathways, and induce DNA mutations.leading to cell cancer.This is currently one of the important mechanisms of ATO nephrotoxicity.Apoptosis, DNA methyl a- tion caused by ATO are also causes of nephrotoxicity.This article summarizes the research and prevention of ATO nephrotoxicity mechanism.
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Aim To study the nephrotoxicity effects of the main monomers in Zuojin Pills. Methods CCK-8 and high-content toxicity screening were used to preliminarily screen the main alkaloids in Zuojin Pills that may cause renal cell damage. Further, by confirmation of cell morphology, release rate of lactate dehydrogenase and cytochrome C, and expression of apoptosis-related proteins, the alkaloids causing cell damage were preliminarily identified, providing in vitro toxicological evidence for the compatibility of components of traditional Chinese medicine and compatibility attenuation. Results Preliminary screening using CCK-8 method and high-content technology showed that evodiamine (EVO) could significantly reduce cell number, increase cell membrane permeability, and reduce mitochondrial membrane potential. In addition, cell morphology, apoptosis and cytochrome C expression were consistent with the results of high-content screening. Western blot experiments indicate that EVO could induce apoptosis and cause renal cell damage. Conclusions EVO can obviously cause renal cell damage, and may induce apoptosis by affecting mitochondria, cytochrome C and cell membrane permeability.
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OBJECTIVE@#To investigate the protective effects of Schisandra chinensis oil (SCEO) against aristolochic acid I (AA I)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism.@*METHODS@#C57BL/6 mice were randomly divided into 5 groups according to a random number table, including control group, AA I group, and AA I +SCEO (0.25, 0.5 and 1 g/kg) groups (n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration, while the control and AA I groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AA I (5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (SCr), as well as renal malondialdehyde (MDA), glutathione, r-glutamyl cysteingl+glycine (GSH), and superoxide dismutase (SOD) were analyzed using enzyme-linked immunosorbent assay (ELISA). Expressions of hepatic cytochrome P450 1A1 (CYP1A1), CYP1A2, and nad(p)hquinonedehydrogenase1 (NQO1) were analyzed using ELISA, quantitative real-time polymerase chain reaction (qPCR) and Western blot, respectively. In vitro, SCEO (40 µ g/mL) was added 12 h before treatment with AA I (40 µ mol/mL for 48 h) in human renal proximal tubule cell line (HK-2), then apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry.@*RESULTS@#SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL+ staining in the kidney tissues of mice with AA I-induced nephrotoxicity, and reduced serum levels of ALT, AST, BUN and SCr (P<0.01 or P<0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney, containing MDA, GSH and SOD (P<0.01 or P<0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues (P<0.01 or P<0.05). Besides, in vitro studies also demonstrated that SCEO 40 µ g/mL inhibited apoptosis and ROS generation (P<0.05 or P<0.01).@*CONCLUSIONS@#SCEO can alleviate AA I-induced kidney damage both in vivo and in vitro. The protective mechanism may be closely related to the regulation of metabolic enzymes, thereby inhibiting apoptosis and ROS production.
Subject(s)
Animals , Mice , Apoptosis , Aristolochic Acids/toxicity , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1A2/metabolism , Glutathione/metabolism , Kidney/drug effects , Kidney Diseases/drug therapy , Mice, Inbred C57BL , Oxidative Stress , Plant Oils/therapeutic use , Protective Agents/therapeutic use , Reactive Oxygen Species/metabolism , Schisandra , Superoxide Dismutase/metabolismABSTRACT
OBJECTIVE To study the nephrotoxicity of the extracts from different parts o f Miao medicine Wikstroemia indica in healthy rats ，and to provide reference for the study of its toxicity mechanism and clinical drug use. METHODS Using 70％ ethanol as solvent ，total ethanol extract of W. indica was extracted with diacolation method. After dispersing the above extract with water，the fractions of corresponding fractions were obtained with petroleum ether ，ethyl acetate and n-butanol，and the rest was the extract of water fraction. SD rats were randomly divided into total ethanol extract group ，petroleum ether fraction group ，ethyl acetate fraction group ，n-butanol fraction group ，water fraction group and blank group ，with 12 rats in each group （half male and half female ）. The rats in the administration groups were given the corresponding dose of drug solution intragastrically （total ethanol extract 317.520 mg/kg，petroleum ether fraction 7.875 mg/kg，ethyl acetate fraction 78.435 mg/kg，n-butanol fraction 53.865 mg/kg and water fraction 76.545 mg/kg），once a day ，for conse- cutive 2 weeks，and then stopped taking drug for 2 weeks； rats in the blank group were given equal volume of 1.0％ . sodium carboxymethyl cellulose solution intragastrically. Duringthe experiment ，the general conditions of rats were observed. The samples of urine （on the 14th and 28th day ），serum and bilateral renal tissues （on the 15th and 29th day ）were taken respectively，the renal index was calculated ，the levels of @qq.com renal function indexes in serum and urine were detected ，and the pathomorphological changes of renal tissues were observed. RESULTS During administration ，compared with blank group ，the rats in the total ethanol extract group and ethyl acetate fraction group showed poisoning behavior and activity characteristics such as mental depression ，decreased activity and diet ，thin stool and decreased body mass. The mental state of the rats in the petroleum ether fraction group ，n-butanol fraction group and water fraction group were slightly worse than that in blank group，and slightly decreased activity and diet as well as thin stool ，and slowly increased body mass were found ；however，there was no significant difference in anal temperature in each group. After 2 weeks of administration ，the renal index in total ethanol extract group ，the serum levels of N-acetylglucosaminidase（NAG），urea nitrogen （BUN）and creatinine （Cr）in total ethanol extract group and ethyl acetate fraction group ，serum level of NAG in n-butanol fraction group and serum level of Cr in water fraction group ，as while as NAG levels in urine of rats in total ethanol extract group and petroleum ether fraction group ，NAG and urinary protein levels in urine of rats in ethyl acetate fraction group were increased significantly （P＜0.05 or P＜0.01）. In the pathomorphological observation ，renal tubules showed different degrees of unclear structure ，cell swelling and a few cell necrosis in the total ethanol extract group ，petroleum ether fraction group and ethyl acetate fraction group ，accompanying by glomerular pyknosis，renal tubular sclerosis and inflammatory cell infiltration ，compared with blank group. After drug withdrawal ，the mental state of rats in the administration groups were significantly improved ，the amount of activity and diet increased ，and the stool tended to be normal. Two weeks after drug withdrawal and recovery ，the levels of above indexes in serum and urine of rats in administration groups returned to be close to that in blank group （P＞0.05）；the glomerular structure of rats in each administration group gradually recovered clearly ，and cell swelling and inflammatory cell infiltration were rare in total ethanol extract group ， petroleum ether fraction group and ethyl acetate fraction group. CONCLUSIONS The total ethanol extract ，petroleum ether fraction and ethyl acetate fraction of Miao medicine W. indica have certain nephrotoxicity and reversibility. The toxic component may