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The present study investigated the protective role of antioxidant (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD), an organoselenium compound, against the renal injury induced by cisplatin in rats. Canola oil or BPD (50mgkg 1 ) was administered orally by gavage once a day for 6days to rats. The first dose of BPD was given 24h before a single intraperitoneal injection of saline or cisplatin (7mgkg 1 ). At day 7, animals were killed and parameters related to renal injury were determined. The histological analysis showed that cisplatin caused renal injury in rats, which was accompanied by an increase in urea and creatinine levels in plasma. The increase of plasma creatinine levels negatively correlated with renal antioxidant defenses including ascorbic acid (AA) and reduced glutathione (GSH) content as well as glutathione S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) activities. As revealed by histological analysis, BPD ameliorated tubular injury in rat kidney and reduced plasma markers altered by cisplatin. The administration of BPD to rats attenuated the reduction of renal AA and GSH content in animals exposed to cisplatin. The decrease of GST activity, but not GPx and CAT activities, in rats exposed to cisplatin was totally reversed by BPD administration. BPD was also effective in attenuating the inhibition of a sulfhydryl enzyme sensitive to oxidative stress, d-aminolevulinic dehydratase, in kidneys of rats exposed to cisplatin. The present study demonstrated that BPD reduced renal injury induced by cisplatin in rats and this effect seems to be related to antioxidant mechanisms. Copyright © 2012 John Wiley &S ons, Ltd.

Peroxisome proliferator-activated receptor-g (PPAR-g) agonists not only improve metabolic abnormalities ofdiabetes and consequent diabetic nephropathy, but they also protect against non-diabetic kidney disease in experimentalmodels. Here, we investigated the effect of PPAR-g agonist pioglitazone against acute renal injury on a cisplatin modelin mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10mgkg –1 ). Pioglitazone wasadministered for six consecutive days in doses of 15 or 30mgkg –1 day –1 , per os (p.o.), starting 3days before cisplatin injection.Cisplatintreatmenttomiceinducedamarkedrenalfailure,characterizedbyasignificantincreaseinserumureaandcreatininelevels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levelsof non-enzymatic antioxidant defenses [glutathione (GSH) and as corbic acid levels] and components of the enzymatic antioxidantdefenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and andglutathione S-transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against theincrease in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazoneadministration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protectedagainst the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These resultsindicated that pioglitazone has a protective effectagainstcisplatin-inducedrenal damagein mice.The protection ismediatedby preventing the decline of antioxidant status. The results have implications in use of PPAR-g agonists in human applicationfor protecting against drugs-induced nephrotoxicity. Copyright © 2012 John Wiley & Sons, Ltd.Keywords: peroxisome proliferator-activated receptor-g; pioglitazone; cisplatin; nephrotoxicity; mice

Organoselenium compounds have important pharmacological properties. However, these compounds can cause toxicity, typically related to oxidation of endogenous thiols. The aim of this study was to investigate whether 2,2′-dithienyl diselenide (DTDS) has potential toxicity in vitro and in vivo. Therefore, sulfhydryl-containing enzyme activities, δ-aminolevulinic acid dehydratase (δ-ALA-D) and Na+–K+-ATPase were used to predict DTDS toxicity in rat brain homogenate in vitro. In in vivo experiments, a DTDS administration (50 or 100 mg kg−1, p.o.) to rats was performed and toxicological parameters were determined. DTDS inhibited δ-ALA-D (IC50 2 µm) and Na+–K+-ATPase (IC50 17 µm) activities in vitro. The inhibitory effect of DTDS on δ-ALA-D and Na+–K+-ATPase activities was restored by dithiothreitol. DTDS (5–25 µm) elicited a thiol oxidase-like activity. In vivo, DTDS (50 and 100 mg kg−1) caused systemic toxicity, evidenced by a decrease in water and food intakes and body weight gain, as well as the death of rats. DTDS at the dose of 100 mg kg−1 increased plasma alanine and aspartate aminotransferase activities and decreased urea levels. At 50 and 100 mg kg−1, it increased lipid peroxidation levels. At the highest dose, DTDS inhibited δ-ALA-D activity. By contrast, Na+–K+-ATPase activity and antioxidant defense were not altered in the brains of rats exposed to DTDS. In conclusion, interaction with the cisteinyl residues seems to mediate the inhibitory effect of DTDS on sulfhydryl-containing enzymes in vitro. In addition, high oral doses of DTDS induce toxicity in rats. Copyright © 2011 John Wiley & Sons, Ltd.

This study was designed to investigate the influence of 2-methyl-6-phenylethynyl pyridine hydrochloride (MPEP), an antagonist of metabotropic glutamate receptor subtype 5, in lipopolysaccharide (LPS) and d-galactosamine (d-GalN)-induced fulminant hepatic failure in mice. Mice were given an intraperitoneal injection of 50 µg kg−1 LPS and 500 mg kg−1d-GalN. MPEP (1, 5 and 25 mg kg−1) was administered intraperitoneally 1 h before LPS/d-GalN injection. Twenty-four hours after administration of LPS/d-GalN, plasma was collected and used for biochemical assays. Mice were euthanized and histological analysis and toxicological parameters were carried out in the liver. MPEP, at all doses tested, protected against the increase in aspartate and alanine aminotransferase activities induced by LPS/d-GalN exposure. Ascorbic acid levels were not altered in all experimental groups. Glutathione S-transferase activity was increased by administration of LPS/d-GalN and MPEP did not modify the enzyme activity in mice. MPEP, at the doses of 5 and 25 mg kg−1, was effective in protecting against the decrease in catalase activity caused by LPS/d-GalN administration in mice. The histological data showed that sections of liver from LPS/d-GalN-exposed mice presented extensive injuries. MPEP, at all doses tested, reduced the scores of liver damage and markedly ameliorated the degree of liver damage. The hepatoprotective effect of MPEP on fulminant hepatic failure induced by LPS and d-GalN in mice was demonstrated. Copyright © 2009 John Wiley & Sons, Ltd.