Acetaminophen induces alterations to the renal tubular ultrastructure in a rat model of acute nephrotoxicity protected by resveratrol and quercetin / El acetaminofeno induce alteraciones en la ultraestructura tubular renal en un modelo de rata con nefrotoxicidad aguda protegida por resveratrol y quercetina

Acetaminophen (also called paracetamol, or APAP) induced nephrotoxicity is reported after accidental or intentional ingestion of an overdose of the drug. Renal tubular ultrastructural alterations induced by APAP overdose associated with the induction of biomarkers of kidney injury have not been investigated before. Also, we investigated whether the combined polyphenolic anti-inflammatory and antioxidants agents, resveratrol (RES) and quercetin (QUR) can protect against APAP-induced acute kidney injury. The model group of rats received a single dose of APAP (2 g/kg), whereas the protective group of rats was pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP. All rats were then sacrificed one day post APAP ingestion. Harvested kidney tissues were prepared for transmission electron microscopy (TEM) staining and blood samples were assayed for urea, creatinine, and biomarkers of inflammation and oxidative stress. TEM images and blood chemistry analysis showed that APAP overdose induced kidney damage as demonstrated by substantial alterations to the proximal convoluted tubule ultrastructure, and a significant (p<0.05) increase in urea, creatinine, tumor necrosis factor-alpha (TNF-a), and malondialdehyde (MDA) blood levels, which were protected by RES+QUR. These findings indicate that APAP induces alterations to the renal tubular ultrastructure, which is inhibited by resveratrol plus quercetin, which also decreases blood levels of kidney injury biomarkers.

El objetivo de este trabajo fue estudiar la nefrotoxicidad inducida por acetaminofeno (también llamado paracetamol o APAP) después de la ingestión accidental o intencional de una sobredosis de la droga. Las alteraciones ultraestructurales tubulares renales inducidas por sobredosis de APAP asociadas con la inducción de biomarcadores de daño renal no se han investigado. Además, estudiamos si los agentes combinados antiinflamatorios y antioxidantes polifenólicos, el resveratrol (RES) y la quercetina (QUR) pueden proteger contra la lesión renal aguda inducida por APAP. El grupo modelo de ratas recibió una dosis única de APAP (2 g / kg), mientras que el grupo protector de ratas se trató previamente durante 7 días con dosis combinadas de RES (30 mg / kg) y QUR (50 mg / kg) antes de recibir una dosis única de APAP. Todas las ratas se sacrificaron un día después de la ingestión de APAP. Los tejidos renales fueron preparados para el análisis a través de la microscopía electrónica de transmisión (MET). En las muestras de sangre se determinaron la urea, creatinina y los biomarcadores de inflamación y estrés oxidativo. Las imágenes MET y el análisis químico de la sangre mostraron que la sobredosis de APAP inducía daño renal, como lo demuestran las alteraciones sustanciales en la ultraestructura del túbulo contorneado proximal, y además, de un aumento significativo (p <0,05) de la urea, creatinina, factor de necrosis tumoral alfa y niveles sanguíneos de malondialdehído, protegidos por RES + QUR. Estos hallazgos indican que APAP induce alteraciones en la ultraestructura tubular renal, inhibida por el resveratrol más quercetina, que también disminuye los niveles sanguíneos de biomarcadores de daño renal.

Renal histological alterations induced by acute exposure of titanium dioxide nanoparticles / Alteraciones histológicas renales inducidas por la exposición aguda de nanopartículas de dióxido de titanio

SUMMARY: Titanium dioxide nanoparticles (TiO2 NPs) are widely used in many commercial products, nanomedicine, agriculture, personal care products, different industries and pharmaceutical preparations with potential risk in human health and the environment. The current work was conducted to investigate the renal damage that might be induced by the acute toxicity TiO2 NPs. A total of 40 healthy male adult Wistar albino rats (Rattus norvegicus) were exposed to TiO2 NPs (126, 252, 378 mg/kg bw) for 24 and 48 h. Fresh portions of the kidneys from each rat were processed for histological and histochemical alterations. In comparison with respective control rats, exposure to TiO2 NPs has marked the following glomerular, tubular and interstitial alterations including the followings: glomerular congestion, Bowman's capsule swelling and dilatation, inflamed glomeruli, renal tubules cloudy swelling, karyorrhexis, karyolysis, infiltration of inflammatory cells, congestion, necrosis, hydropic degeneration, dilatation and congestion of blood vessels, hyaline droplets and hyaline casts precipitation, interstitial edema and fibrosis. From the findings of the current work one may conclude that TiO2 NPs are capable of inducing kidney damage with more insulation in the cortex and the proximal convoluted tubules than the medulla and the distal ones respectively. In addition, it might be concluded that renal damage induced by these nanomaterials is dose and duration of exposure dependent. Further hematological, biochemical, immunohistochemical, and ultra-structural studies are recommended.

RESUMEN: Las nanopartículas de dióxido de titanio (TiO2 NP) se usan ampliamente en muchos productos comerciales, nanomedicina, agricultura, productos para el cuidado personal, diferentes industrias y preparaciones farmacéuticas con riesgo potencial para la salud humana y el medio ambiente. El trabajo actual se realizó para investigar el daño renal que podría ser inducido por la toxicidad aguda NP de TiO2. Un total de 40 ratas Wistar albinas adultas sanas (Rattus norvegicus) fueron expuestas a TiO2 NP (126, 252, 378 mg / kg de peso corporal) durante 24 y 48 h. Las muestras de los riñones de las ratas se procesaron para estudios histológicos e histoquímicos. En comparación con las ratas control, la exposición de las ratas a TiO2 NP presentaron las siguientes alteraciones glomerulares, tubulares e intersticiales: congestión glomerular, dilatación de la cápsula de Bowman, inflamación glomerular, túbulos renales aumentados, cariorrexis, cariólisis, infiltración de células inflamatorias, congestión, necrosis, degeneración hidrópica, dilatación y congestión de vasos sanguíneos, gotas y precipitaciones hialina, edema intersticial y fibrosis. A partir de los hallazgos del trabajo actual, se puede concluir que las NP de TiO 2 son capaces de inducir daño renal con más aislamiento en la corteza y en los túbulos contorneados proximales que en la médula y los túbulos contorneados distales, respectivamente. Además, se podría concluir que el daño renal inducido por estos nanomateriales depende de la dosis y la duración de la exposición. Se recomiendan estudios adicionales hematológicos, bioquímicos, inmunohistoquímicos y ultraestructurales.

Serum concentrations and renal expressions of IL-1 and TNF-a early after hemorrhage in rats under the effect of glibenclamide

ABSTRACT PURPOSE: To investigate changes in the serum concentration and renal expression of IL-1 and TNF-α cytokines in rats that received sevoflurane and glibenclamide prior to hemorrhage. METHODS: Two groups of sevoflurane-anesthetized Wistar rats (n=10): G1 (control) and G2 (glibenclamide, 1 µg/g i.v.); hemorrhage of 30% blood volume (10% every 10 min), with replacement using Ringer solution, 5 ml/kg/h. Serum concentrations of IL-1 and TNF-α were studied in the first hemorrhage (T1) and 50 min later (T2), renal expression, at T2. RESULTS: In serum, G1 TNF-α (pg/mL) was T1=178.6±33.5, T2=509.2±118.8 (p<0.05); IL-1 (pg/mL) was T1=148.8±31.3, T2=322.6±115.4 (p<0.05); in G2, TNF-α was T1=486.2±83.6, T2=261.8±79.5 (p<0.05); IL-1 was T1=347.0±72.0, T2= 327.3±90.9 (p>0.05). The expression of TNF-α and IL-1 in the glomerular and tubular cells was significantly higher in the G2 group. CONCLUSIONS: Hemorrhage and glibenclamide elevated TNF-α and IL-1 concentrations in serum and kidneys. High levels of TNF-α already present before the hemorrhage in the glibenclamide group may have attenuated the damages found in the kidneys after the ischemia event.

Acute hyperglycemia prevents dexmedetomidine-induced preconditioning against renal ischemia-reperfusion injury

PURPOSE: To investigate the effects of acute hyperglycemia on dexmedetomidine-induced preconditioning against renal ischemia-reperfusion injury. METHODS: Sprague-Dawley rats were randomly arranged to the normoglycemic (NG) or hyperglycemic group (HG), with each group further divided into sham (no I/R injury), I/R (ischemia-reperfusion) and dex (given by dexmedetomidine) groups. Acute hyperglycemia was induced by intraperitoneal injection (i.p.) of 25% glucose (3 g/kg) 45 min before ischemia. Dexmedetomidine (50 μg/kg, i.p.) was administrated 30 min before induction of ischemia. Renal function, histology, apoptosis, expression of Bax, Bcl-2 and phosphorylated AKT (p-AKT) were detected. RESULTS: I/R insult significantly increased the serum levels of blood urea nitrogen and creatinine, apoptotic tubular epithelial cells, expression of Bax and p-AKT, but decreased Bcl-2 expression. All these changes were further enhanced by hyperglycemia (p<0.05). In hyperglycemic condition, there was no statistically difference between the I/R group and Dex group in all the aforementioned detection indexes (p>0.05). CONCLUSION: Acute hyperglycemia attenuates dexmedetomidine-induced preconditioning against renal ischemia-reperfusion injury in non-diabetic rats. .

El Campus Virtual de Salud Pública: seis años de formar recursos humanos en México / Virtual Campus of Public Health: six years of human resources education in Mexico

Este trabajo muestra, desde el punto de vista de la normatividad de la Organización Panamericana de la Salud (OPS), el proceso de gestación, la metodología de implementación y los resultados obtenidos de la iniciativa de formación de recursos humanos en salud vía e-learning a través del Campus Virtual de Salud Pública de la Universidad de Guadalajara, México, a seis años de su inicio. Se trata de un informe especial del trabajo realizado por el comité institucional del campus virtual en la región occidental de México para generar un portal de Internet que se ajustara a los lineamientos del Modelo Estratégico establecido por el Nodo México y la OPS para la Región de las Américas. Este Campus Virtual inició sus actividades en el año 2007. Su filosofía es el uso de software libre y la colaboración entre instituciones. El nodo fue implementado en un año y ha logrado capacitar a más de 500 profesionales de la salud a través de cursos virtuales, su plataforma educativa y un repositorio de recursos virtuales de aprendizaje con interoperabilidad con los repositorios de México y de la Región de las Américas. El comité del Campus Virtual de la Universidad de Guadalajara ha intentado respetar lo más posible al modelo propuesto, lo que ha permitido cumplir la mayoría de los objetivos fijados en el plan de trabajo inicial, aunque ha enfrentado una serie de dificultades administrativas y de motivación de sus integrantes.

This paper discusses the gestation process, implementation methodology, and results obtained from the initiative to use e-learning to train human resources for health, six years after the launch of the Virtual Campus of Public Health of the University of Guadalajara (Mexico); the discussion is framed by Pan American Health Organization (PAHO) standards and practices. This is a special report on the work done by the institutional committee of the Virtual Campus in western Mexico to create an Internet portal that follows the guidelines of the strategic model established by Nodo México and PAHO for the Region of the Americas. This Virtual Campus began its activities in 2007, on the basis of the use of free software and institutional collaboration. Since the initial year of implementation of the node, over 500 health professionals have been trained using virtual courses, the node's educational platform, and a repository of virtual learning resources that are interoperable with other repositories in Mexico and the Region of the Americas. The University of Guadalajara Virtual Campus committee has followed the proposed model as much as possible, thereby achieving most of the goals set in the initial work plan, despite a number of administrative challenges and the difficulty of motivating committee members.

Papel de las mitocondrias y el estrés oxidativo en el proceso inflamatorio renal / Mitochondria and oxidative stress participation in renal inflammatory process

La muerte celular programada y la fibrosis renal son procesos inherentes a la enfermedad renal crónica y, en tal sentido, ha sido recientemente descripta una clara desregulación de la maquinaria respiratoria mitocondrial en pacientes con enfermedad renal crónica asociada con un aumento del estrés oxidativo. Las células tubulares lesionadas vinculadas a los macrófagos intersticiales y miofibroblastos producen citoquinas y factores de crecimiento que promueven un estado inflamatorio, inducen la apoptosis de las células tubulares y facilitan la acumulación de matriz extracelular. La angiotensina II desempeña un papel central en la fibrogénesis renal y conduce a una rápida progresión de la enfermedad renal crónica. Los niveles crecientes de la angiotensina II inducen citoquinas pro-inflamatorias, la activación de NF-kB, moléculas de adhesión, quimiocinas, factores de crecimiento y estrés oxidativo. Toda la evidencia actual sugiere que la angiotensina II aumenta el estrés oxidativo mitocondrial, regula la inducción de apoptosis y condiciona al estado inflamatorio. Por lo tanto, existiría un papel determinante de las mitocondrias y el estrés oxidativo en el proceso inflamatorio renal. Finalmente, esta revisión resume nuestro actual conocimiento acerca de los posibles mecanismos que contribuirían con la apoptosis modulada por la inflamación y/o el estrés oxidativo durante la enfermedad renal crónica. Además, se propone un nuevo concepto de herramientas anti-inflamatorias que regulan el estrés oxidativo mitocondrial lo cual afectaría directamente al proceso inflamatorio y la apoptosis. Esta idea podría tener consecuencias atractivas sobre el tratamiento de patologías inflamatorias renales y de otras afines.

The apoptosis and renal fibrosis are processes inherent to the chronic kidney disease, and consequently a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with chronic renal disease associated to an increase of the oxidative stress. The injured tubular cells linked to the interstitial macrophages and myofibroblasts produce cytokines and growth factors that encourage an inflammatory condition, inducing the apoptosis of the tubular cells and enabling the accumulation of the extracellular matrix. The angiotensin II has a central role in the renal fibrogenesis leading to a rapid progression of the chronic kidney disease. The growing levels of the angiotensin II induce pro-inflammatory cytokines, the activation of NF-kB, adhesion molecules,chemokines, growth factors, and oxidative stress. The current evidence suggests that the angiotensin II increases the mitochondrial oxidative stress, regulates the induction of the apoptosis and conditions the inflammatory process. Therefore the mitochondria and the oxidative stress would play a determinant role in the renal inflammatory process. Finally, this review summarizes our present knowledge regarding the possible mechanisms that would contribute to the apoptosis conditioned by inflammation and/or oxidative stress during the chronic renal disease. Additionally, a new concept of the anti-inflammatory tools is proposed to regulate the mitochondrial oxidative stress that would directly affect the inflammatory process and apoptosis. This concept could have positive consequences on the treatment of renal inflammatory pathologies and related diseases.

The renoprotective effects of pentoxifylline: beyond its role in diabetic nephropathy

No abstract available.

Prevention of renal ischemia/reperfusion injury in rats using acetylcysteine after anesthesia with isoflurane / Prevenção de lesão de isquemia/reperfusão em ratos com acetilcisteína após anestesia com isoflurano

PURPOSE: To evaluate the effect of N-acetylcysteine, as a renoprotective agent, when administered early after anesthesia induction, against ischemia/reperfusion injury in rats anesthetized with isoflurane. METHODS: Eighteen male Wistar rats weighing > 300g were anesthetized with isoflurane. The internal jugular vein and the left carotid artery were dissected and cannulated. The animals were randomly divided into GAcetyl, receiving intravenous N-acetylcysteine, 300mg/kg, and GIsot, isotonic saline. After 30 minutes, right nephrectomy was performed and the left renal artery was clamped during 45 minutes. The animals were sacrificed after 48 hours and blood samples were taken after anesthetic induction and upon sacrificing of the animals to evaluate blood creatinine. The kidneys were sent for histological analysis. RESULTS: The variation in serum creatinine was 2.33mg/dL ± 2.21 in GAcetyl and 4.38mg/dL ± 2.13 in GIsot (p=0.074). Two animals presented intense tubular necrosis in GAcetyl, compared to 5 in GIsot. Only GAcetyl presented animals free of tubular necrosis (two) and tubular degeneration (one). CONCLUSION: After renal ischemia/reperfusion, the rats which were given N-acetylcysteine presented less variation in serum creatinine and milder kidney injuries than the control group.

OBJETIVO: Avaliar o efeito da N-acetilcisteína na proteção renal contra lesão de isquemia/reperfusão, quando administrada logo após a indução anestésica, em ratos anestesiados com isoflurano. MÉTODOS: Dezoito ratos Wistar machos pesando mais que 300g foram anestesiados com isoflurano. A jugular interna direita e a carótida esquerda foram dissecadas e canuladas. Os animais foram distribuídos aleatoriamente em GAcetil, recebendo N-acetilcisteína por via intravenosa, 300mg/kg, e GIsot, solução salina. Foi realizada nefrectomia direita e clampeamento da artéria renal esquerda por 45 min. Os animais foram sacrificados após 48h, sendo colhidas amostras sanguíneas após a indução anestésica e ao sacrifício dos mesmos para avaliar a creatinina sérica. Realizou-se histologia renal. RESULTADOS: A variação da creatinina foi 2,33mg/dL ± 2,21 no GAcetil e 4,38mg/dL ± 2,13 no GIsot (p=0,074). Dois animais apresentaram necrose tubular intensa no GAcetil, comparados a cinco no GIsot. Apenas GAcetil apresentou animais livres de necrose tubular (dois) e degeneração tubular (um). CONCLUSÃO: Após isquemia/reperfusão renais, os ratos aos quais se administrou N-acetilcisteína apresentaram menor variação na creatinina sérica e lesões renais mais leves que o grupo controle.

Effect of Phosphodiesterase Inhibitor on Diabetic Nephropathy

No abstract available.

Phosphodiesterase Inhibitor Improves Renal Tubulointerstitial Hypoxia of the Diabetic Rat Kidney

BACKGROUND/AIMS: Renal hypoxia is involved in the pathogenesis of diabetic nephropathy. Pentoxifyllin (PTX), a nonselective phosphodiesterase inhibitor, is used to attenuate peripheral vascular diseases. To determine whether PTX can improve renal hypoxia, we investigated its effect in the streptozocin (STZ)-induced diabetic kidney. METHODS: PTX (40 mg/kg, PO) was administered to STZ-induced diabetic rats for 8 weeks. To determine tissue hypoxia, we examined hypoxic inducible factor-1alpha (HIF-1alpha), heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1) levels. We also tested the effect of PTX on HIF-1alpha in renal tubule cells. RESULTS: PTX reduced the increased protein creatinine ratio in diabetic rats at 8 weeks. HIF-1alpha, VEGF, and GLUT-1 mRNA expression increased significantly, and the expression of HO-1 also tended to increase in diabetic rats. PTX significantly decreased mRNA expression of HIF-1alpha and VEGF at 4 and 8 weeks, and decreased HO-1 and GLUT-1 at 4 weeks. The expression of HIF-1alpha protein was significantly increased at 4 and 8 weeks in tubules in the diabetic rat kidney. PTX tended to decrease HIF-1alpha protein expression at 8 weeks. To examine whether PTX had a direct effect on renal tubules, normal rat kidney cells were stimulated with CoCl2 (100 microM), which enhanced HIF-1alpha mRNA and protein levels under low glucose conditions (5.5 mM). Their expressions were similar even after high glucose (30 mM) treatment. PTX had no effect on HIF-1alpha expression. CONCLUSIONS: PTX attenuates tubular hypoxia in the diabetic kidney.

Histologic alterations of rat kidneys perfused with a Euro-Collins diltiazem solution / Alterações histológicas ocorridas em rins de ratos perfundidos com solução de Euro-Collins associada à diltiazem

PURPOSE: Analyse the histologic changes of rat kidneys perfused with isotonic saline solution (ISS), Euro-Collins solution (ECS) and Euro-Collins solution with diltiazem (ECSD). METHODS: Thirty-six Wistar rats were used divided equally, as follow: group A (ISS), group B (ECS) and group C (ECSD). Through a catheter placed into the abdominal aorta, a renal perfusion was performed using a solution according to the group to which the animal belonged. After the complete perfusion, bilateral nephrectomy was performed and the organs were preserved under hypothermia for five distinct periods of time. Glomerulus and tubule were evaluated through optical microscopy. RESULTS: Renal perfusion with ECS and ECSD proved effectiveness in the preservation of the organs up to 36 hours and an increase in the percentage of injured glomeruli was noticed only in the period of 48 hours. CONCLUSIONS: The results showed that exists an association between the tubular injury and the glomeruli lesion degree; kidneys with a higher degree of tubular damage were related to severe glomerular lesion. Also, the addition of a calcium channel blocker, diltiazem, to the ECS for the renal perfusion does not decrease the percentage of glomerular lesion.

OBJETIVO: Analisar as alterações histológicas nos rins de ratos perfundidos com solução salina isotônica (ISS), solução Euro-Collins (ECS) e solução Euro-Collins com diltiazem (ECSD). MÉTODOS: Foram divididos, de forma igual, 36 ratos Wistar, como se segue: grupo A (ISS), grupo B (ECS), grupo C (ECSD). Através de um cateter localizado na aorta abdominal, foi realizada a perfusão renal com a solução de acordo com o grupo ao qual o animal pertencia. Após a perfusão total, realizou-se nefrectomia bilateral com a preservação dos órgãos sob hipotermia por cinco períodos distintos de tempo. Glomérulos e túbulos foram avaliados por microscopia óptica. RESULTADOS: Tanto a perfusão renal com ECS quanto a com ECSD provaram sua efetividade na preservação dos órgãos em até 36 horas e aumento da porcentagem de glomérulos injuriados foi notada apenas no período de 48 horas. CONCLUSÕES: Os resultados mostraram haver uma correlação entre a injúria tubular e o grau de lesão glomerular; rins com um maior grau de dano tubular foram relacionados com lesão glomerular severa. Além disso, a adição de um bloqueador de canal de cálcio, diltiazem, à ECS para a perfusão renal não diminui a porcentagem de lesão glomerular.

Diminution of oxalate induced renal tubular epithelial cell injury and inhibition of calcium oxalate crystallization in vitro by aqueous extract of Tribulus terrestris

PURPOSE: Recurrence and persistent side effects of present day treatment for urolithiasis restrict their use, so an alternate solution, using phytotherapy is being sought. The present study attempted to evaluate the antilithiatic properties of Tribulus terrestris commonly called as “gokhru” which is often used in ayurveda to treat various urinary diseases including urolithiasis. MATERIALS AND METHODS: The activity of Tribulus terrestris was investigated on nucleation and the growth of the calcium oxalate (CaOx) crystals as well as on oxalate induced cell injury of NRK 52E renal epithelial cells. RESULTS: Tribulus terrestris extract exhibited a concentration dependent inhibition of nucleation and the growth of CaOx crystals. When NRK-52E cells were injured by exposure to oxalate for 72 h, Tribulus terrestris extract prevented the injury in a dose-dependent manner. On treatment with the different concentrations of the plant, the cell viability increased and lactate dehydrogenase release decreased in a concentration dependent manner. CONCLUSION: The current data suggests that Tribulus terrestris extract not only has a potential to inhibit nucleation and the growth of the CaOx crystals but also has a cytoprotective role. Our results indicate that it could be a potential candidate for phytotherapy against urolithiasis.

Post-treatment Effects of Erythropoietin and Nordihydroguaiaretic Acid on Recovery from Cisplatin-induced Acute Renal Failure in the Rat

5-Lipoxygenase inhibitor and human recombinant erythropoietin might accelerate renal recovery in cisplatin-induced acute renal failure rats. Male Sprague-Dawley rats were randomized into four groups: 1) normal controls; 2) Cisplatin group-cisplatin induced acute renal failure (ARF) plus vehicle treatment; 3) Cisplatin+nordihydroguaiaretic acid (NDGA) group-cisplatin induced ARF plus 5-lipoxygenase inhibitor treatment; 4) Cisplatin+erythropoietin (EPO) group-cisplatin induced ARF plus erythropoietin treatment. On day 10 (after 7 daily injections of NDGA or EPO), urea nitrogen and serum Cr concentrations were significantly lower in the Cisplatin+NDGA and Cisplatin+EPO groups than in the Cisplatin group, and 24 hr urine Cr clearances were significantly higher in the Cisplatin+EPO group than in the Cisplatin group. Semiquantitative assessments of histological lesions did not produce any significant differences between the three treatment groups. Numbers of PCNA(+) cells were significantly higher in Cisplatin, Cisplatin+NDGA, and Cisplatin+EPO groups than in normal controls. Those PCNA(+) cells were significantly increased in Cisplatin+NDGA group. These results suggest that EPO and also NDGA accelerate renal function recovery by stimulating tubular epithelial cell regeneration.

BTCI enhances guanylin-induced natriuresis and promotes renal glomerular and tubular effects

Guanylin and uroguanylin are small cysteine-rich peptides involved in the regulation of fluid and electrolyte homeostasis through binding and activation of guanylyl cyclases signaling molecules expressed in intestine and kidney. Guanylin is less potent than uroguanylin as a natriuretic agent and is degraded in vitro by chymotrypsin due to unique structural features in the bioactive moiety of the peptide. Thus, the aim of this study was to verify whether or not guanylin is degraded by chymotrypsin-like proteases present in the kidney brush-border membranes. The isolated perfused rat kidney assay was used in this regard. Guanylin (0.2 µM) induced no changes in kidney function. However, when pretreated by the black-eyed pea trypsin and chymotrypsin inhibitor (BTCI - 1.0 µM; guanylin - 0.2 µM) it promoted increases in urine flow (deltaUF of 0.25 ± 0.09 mL.g-1/min, P < 0.05) and Na+ excretion ( percent delta ENa+ of 18.20 ± 2.17, P < 0.05). BTCI (1.0 µM) also increased percentENa+ (from 22.8 ± 1.30 to 34.4 ± 3.48, P < 0.05, 90 minutes). Furthermore, BTCI (3.0 µM) induced increases in glomerular filtration rate (GFR; from 0.96 ± 0.02 to 1.28 0.02 mL.g-1/min, P < 0.05, 60 minutes). The present paper strongly suggests that chymotrypsin-like proteases play a role in renal metabolism of guanylin and describes for the first time renal effects induced by a member of the Bowman-Birk family of protease inhibitors.

Guanilina e uroguanilina são peptídeos pequenos, ricos em cisteína, envolvidos na regulação da homeostase de fluidos e eletrólitos através da ligação e ativação da guanilato ciclase expressa no intestino e nos rins. A guanilina é menos potente do que a uroguanilina como agente natriurético e é degradada in vitro pela quimiotripsina devido a características estruturais únicas no domínio bioativo do peptídeo. Portanto o objetivo deste trabalho foi verificar se a guanilina é degradada por proteases tipo quimiotripsina, presentes na membrana da borda em escova dos rins. Para esta investigação, foi usado o modelo do rim isolado de rato perfundido. A Guanilina (0,2 µM) não induziu mudanças na função renal. Entretanto, quando pré-tratada com inibidor de tripsina e de quimiotripsina de black-eyed pea (BTCI - 1,0 µM; guanilina - 0,2 µM) promoveu um aumento no fluxo urinário (deltaUF de 0,25 ± 0,09 mL.g-1/min, P < 0,05) e na excreção de Na+ ( por centoDENa+ de 18,20 ± 2,17, P < 0,05). BTCI (1,0 µM) também aumenta por centoENa+ (de 22,8 ± 1,30 a 34,4 ± 3,48, P < 0,0590 minutos). Além disto, BTCI (3,0 µM) induziu um aumento da taxa de filtração glomerular (GFR; de 0,96 ± 0,02 para 1,28 ± 0,02 mL.g-1/min, P < 0,05, 60 minutos). O presente trabalho sugere fortemente que proteases semelhantes à quimiotripsina desempenham um papel no metabolismo renal de guanilinas e descreve, pela primeira vez, os efeitos renais induzidos por um membro da família de inibidores de proteases do tipo Bowman-Birk.

Protective effect of safranal against hexachlorobutadiene-induced nephrotoxicity in rat

Hexachlorobutadiene [HCBD] is a potent nephrotoxin in rodents, which can cause degeneration, necrosis and regeneration in renal tubular epithelial cells. It has been shown that safranal, the active ingredient of saffron, has a protective effect against ischemic injuries. The aim of this study was to examine the protective effect of safranal against HCBD-induced nephrotoxicity in rats. Method: Thirty Wistar albino rats were randomly divided in five groups. The rats received a single dose of corn oil 1ml/kg [group1], HCBD 50mg/kg [group 2], or safranal at doses of 0.5, 0.25 and 0.1 ml/kg one hour before HCBD [50mg/kg] injection [groups 3-5]. All injections were carried out intraperitoneally. Urine samples were collected one day before, and one day after injections. On day 3 the animals were sacrificed and both kidneys were removed. The right kidney was fixed in formalin for histological examination and the left kidney was homogenized for measuring malondialdehyde [MDA]. Blood samples were taken by cardiac puncture and used for the measurement of urea, creatinine, glucose and protein concentrations. Blood urea concentration in HCBD treated group was significantly higher compared with group 3 [p<0.01] and groups 1 and 4 [p<0.001]. There was no significant difference in urea concen-trations between group 5 and HCBD treated group. Urinary concentration of glucose was significantly higher in group 2, compared with groups 1, 3 and 4 [p<0.001] No significant differences were observed in urinary glucose concentrations between HCBD- and safranal [0.1ml/kg]-treated groups. Concentration of protein was also significantly higher in group 5 than those of other tested groups [p<0.001]. Safranal at doses of 0.25 and 0.5ml/kg has a protective effect against HCBD-induced nephrotoxicity in rats

Evaluation of abamectin toxicity on some biochemical constituents and osmoregulation in freshwater fish Oreochromis niloticus [Tilapia niloticus]

Indiscriment use of pesticides have been elevated the risk of contamination in environment and aquatic organisms. Considering to the previous fact, the present study was done to investigate the alterations of some blood constituents and ionic regulation; as well as the histopathological alterations in tissues of gills and kidneys of freshwater fish, Oreochromis niloticus, following prolonged exposure to sub-lethal concentrations of abamectin insecticide at 14 days. The obtained results showed that abamectin treatment caused hypotriglyceridemia and hyperglycemia in fish exposed to the high concentration [103.68 micro gL[-1]]. In addition, hypercholesterolemia was detected in abamectin-exposed fish [by 50.48 and 103. 68 micro gL[-]] after 14 days of exposure. Also, a marked increase in the creatinine level was observed in abamectin-exposed fish by 103.68 micro gL-1 on day 14, with a significant decline in the level of sodium ions [Na[+]] and a significant elevation in the level of chloride ions [Cl[-]] in fish exposed to low concentration [50.48 micro gL[-1]] of abamectin. In contrast, a significant decrease in the level of chloride ions [Cl[-]] was detected in the high concentration of abamectin. Marked decrease in the level of plasma bound calcium [B.Ca] with hypoproteinemia and hypophosphatemia were recorded in fish exposed to low concentration [50.48 micro gL[-1]] of abamectin. On the contrary, a marked enhancement in the triiodothyronine level [T3] was noticed in fish following exposure to 50.48 micro gL[-1] of abamectin. The histopathological studies on the gills and kidneys revealed necrosis of lamella and infiltration of acidophils leukocyte in gills with degenerative changes in kidney tubules were observed at both concentrations of abamectin

Effect of D-alpha-tocopherol on tubular nephron acidification by rats with induced diabetes mellitus

The objective of the present study was to determine if treatment of diabetic rats with D-alpha-tocopherol could prevent the changes in glomerular and tubular function commonly observed in this disease. Sixty male Wistar rats divided into four groups were studied: control (C), control treated with D-alpha-tocopherol (C + T), diabetic (D), and diabetic treated with D-alpha-tocopherol (D + T). Treatment with D-alpha-tocopherol (40 mg/kg every other day, ip) was started three days after diabetes induction with streptozotocin (60 mg/kg, ip). Renal function studies and microperfusion measurements were performed 30 days after diabetes induction and the kidneys were removed for morphometric analyses. Data are reported as means ± SEM. Glomerular filtration rate increased in D rats but decreased in D + T rats (C: 6.43 ± 0.21; D: 7.74 ± 0.45; D + T: 3.86 ± 0.18 ml min-1 kg-1). Alterations of tubular acidification observed in bicarbonate absorption flux (JHCO3) and in acidification half-time (t/2) in group D were reversed in group D + T (JHCO3, C: 2.30 ± 0.10; D: 3.28 ± 0.22; D + T: 1.87 ± 0.08 nmol cm-2 s-1; t/2, C: 4.75 ± 0.20; D: 3.52 ± 0.15; D + T: 5.92 ± 0.19 s). Glomerular area was significantly increased in D, while D + T rats exhibited values similar to C, suggesting that the vitamin prevented the hypertrophic effect of hyperglycemia (C: 8334.21 ± 112.05; D: 10,217.55 ± 100.66; D + T: 8478.21 ± 119.81æm²). These results suggest that D-alpha-tocopherol is able to protect rats, at least in part, from the harmful effects of diabetes on renal function.

Effects of herbicide on the kidneys of two Venezuelan cultured fish: Caquetaia kraussii and Colossoma macropomum (Pisces:Ciclidae and Characeae)

The use of chemical pesticides and herbicides has increased environmental pollution and affected ichthyofauna in the watersheds where they are used.We studied the effect of an herbicide, triazine, on the kidneys of two species (Caquetaia kraussii and Colossoma macropomum )widely found in Caribbean and South American rivers.In Venezuela,these species are abundant and have a high aquaculture potential because they may be cultured and reproduced in captivity.Four kidney samples from juveniles of each species exposed to the herbicide were examined by Transmission Electron Microscopy.Kidney tubule alterations included loss of plasmalemma and cell interdigitations, misshaped mitochondria,decrease in rough endoplasmic reticulum and free polysomes,and the presence of autophagic vacuoles and primary lysosomes.These alterations at the cellular level may explain fish behaviour in terms of kidney tubule pathology,and relative amounts and conditions of organelles within affected cells

Some histological, histochemical and ultrastructural studies on the effect of tobramycin on the convoluted tubules of the kidney of albino rat

Tobramycin is the most active member of all the aminoglycoside antibiotic group acting against gram- negative bacteria. The aim of present study was to detect the effect of tobramycin on tile convoluted tubules in two different dosage regimen. Sixty adult male albino rats were divided into three groups. Group I as control. Group II: included rats which were injected intraperitoneally with daily dose of 4 mg/kg tobramycin in three equally divided doses. Group III: injected with the same previous dose once daily. They were sacrificed after 3,10,14 days of injection and tissue samples from the cortex of each kidney were taken and processed for both light and electron microscopic examination. In group II, by light microscope swelling of the cells lining the convoluted tubules and vacuolation of their cytoplasm as well as brown granules and hemorrhage were observed. The regenerating cells appeared with basophilic cytoplasm. Progressive decrease in succinic dehydrogenase and increase in acid phosphatase enzymatic activities were observed. Ultrastructurally, there were affection of mitochondria and partial or complete loss of microvilli in some tubules were observed. The cytoplasm of some tubules revealed numerous myeloid bodies with various degrees of nuclear degeneration. Dilated basal infoldings and thickened basement membrane was also observed. The previous changes were less evident on administration of the drug in Group III. In conclusion, patients with a previous kidney disease should better avoid the use of this drug whenever possible but if its use is necessary, once daily dosage may be advised for short period

Histological and histochemical study of the toxic effect of sodium fluoride and the possible protective role of sodium selenite on the convoluted tubules of the renal cortex of albino rats

Sodium fluaride is known as a specific and effective dental caries rohylactic agent and its systemic or local application is widely recommended in the recent years. It is also used as antihelminthic against roundworms, and for treatment of osteoporosis and otosclerosis in conjunction with calcium supplements and vitamin D. Moreover, it is used for water fluoridation, and as a rodenticide, disinfectant and fungicide. In recent years, acute and chronic toxicity of fluoride has been reported. The purpose of the recent study was to shed light on the histological [light and electron microcopic] and histochemical changes that might occur in the proximal and distal convoluted tubules of the renal cortex of albino rats following acute and chronic sodium fluoride [NaF] toxicity and to investigate the possible protective effect of sodium selenite [Na[2]SeO[3] administration on such toxicity. The present study was carried out on 80 adult male albino rats. They were divided into two main groups: acute NaF toxicity group and chronic NaF toxicity group, each of them included forty rats and was divided equally into four groups which were control group, NaF group, Na[2]SeO[3] group, and NaF and Na[2]SeO[3] group. In the acute toxicity group, NaF group received a single oral dose or NaF [135mg/kg body weight], Na[2]SeO[3] group received a single oral dose of Na[2]SeO[3] [0.35mg/kg body weight/day], while NaF and Na[2]SeO[3] group received a single oral dose of NaF [135mg/kg body weight] simultaneously with a single oral dose of Na[2]SeO[3] [0.35 mg/kg body weigh/day]. On he other hand, in chronic toxicity group, NaF group received NaF orally in a dose of 6mg/kg body weight/day, Na[2]SeO[3] group received Na+2+Se[SeO[3] orally in a dose of 0.35 mg/kg body weight/day, while NaF and Na+2+SeO[3] group received a daily oral dose of NaF [6mg/kg body weight/day] simultaneously with a daily oral dose of Na[2]SeO[3]]0.35mg/kg body weight/day] for three months. All rats were sacrificed 24 hours after their last dosing by decapitation after ether anesthesia Fresh specimens were taken from the renal cortex of each rat and prepared for the histological study [light microscopic examination using haematoxylin and eosin stain, and electron microscopic examination using the transmission electron microscope], and histochemical study [Periodic Acid-Schiff reaction]. The results of the present study revealed that there were marked histological and histochemical changes in the convoluted renal tubules following acute and chronic NaF toxicity. Moreover, sodium selenite was found to be a safe anti-oxidant, when used in appropriate dose, which could offer protection for the renal tissue in chronic NaF toxicity. Hence, it is recommended as a prophylactic agent given to workers highly exposed to sodium fluoride in their work place