3-nitrotyrosine and bicyclol

This study investigated the protective effects of bicyclol against cisplatin-induced nephrotoxicity and the possible mechanisms in mice. Bicyclol (250 mg/kg, p.o., 5 days) showed significant protection as evidenced by the decrease of elevated serum creatine and blood urea nitrogen, and improvement of histopathological injury induced by cisplatin. The formation of kidney malondialdehyde with a concomitant reduction of reduced glutathione were also inhibited by bicyclol, while the activities of kidney superoxide dismutase, catalase and glutathione peroxidase were all increased, respectively. Bicyclol also inhibited the increase of kidney and serum nitric oxide induced by cisplatin. In addition, induction of induced nitric oxide synthase and nitrotyrosine were suppressed by bicyclol. Bicyclol suppressed cisplatin-induced extracelluar signal regulated kinases 1/2 and p38 mitogen-activated protein kinase activation in the kidney of mice. Results obtained demonstrate that bicyclol pre-administration can prevent the nephrotoxicity induced by cisplatin.

Topics: Animals; Antineoplastic Agents; Biphenyl Compounds; Cisplatin; Disease Models, Animal; Free Radical Scavengers; Glutathione; Kidney; Kidney Diseases; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Kinases; Nitric Oxide; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Tyrosine

The aim of this study was to determine the effect of bicyclol against cisplatin-induced hepatotoxicity and the influence on the antitumour capacity of cisplatin in hepatocarcinoma 22 (H22) tumour-bearing mice. ICR mice were treated with bicyclol (250 mg/kg, orally) 2 hr before the injection of cisplatin (5 mg/kg, intraperitoneally) for 5 days (once daily) after H22 tumour cells were implanted. All animals were killed on the fifth day after cisplatin treatment and tumour weight of each animal was measured. Liver pathological changes were examined by light microscopy and biochemical assay. The expressions of liver inducible nitric oxide synthase (iNOS and nitric oxide synthase 2) and 3-nitrotyrosine were assessed by Western blotting. Bicyclol showed a significant protection as evidenced by the decrease of elevated serum aminotransferases and lactate dehydrogenase, and improvement of histopathological injury induced by cisplatin. The formation of liver malondialdehyde with a concomitant reduction of reduced glutathione was also inhibited by bicyclol, while the activities of liver superoxide dismutase, catalase and glutathione peroxidase were all increased, respectively. In addition, the over expressions of liver iNOS and 3-nitrotyrosine were suppressed by bicyclol. The administration of bicyclol had no affect on the anti-tumour capacity of cisplatin in mice bearing H22 tumour. The hepatoprotective action of bicyclol provides a new approach for preventing the hepatotoxicity induced by cisplatin in the clinic.

Topics: Animals; Antineoplastic Agents; Biphenyl Compounds; Blotting, Western; Carcinoma, Hepatocellular; Cell Line, Tumor; Chemical and Drug Induced Liver Injury; Cisplatin; Drug Interactions; Gene Expression Regulation; L-Lactate Dehydrogenase; Liver; Liver Diseases; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase Type II; Transaminases; Tyrosine