Effect of bicyclol on cisplatin-induced hepatotoxicity in the hepatocarcinoma 22 tumour-bearing mice.
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.
Yu
Ying-Nan
YN
Department of New Drug Development, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Chen
Hui
H
Li
Yan
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D056486:Chemical and Drug Induced Liver Injury; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity*; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008107:Liver Diseases / Q000517:prevention & control*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D000637:Transaminases / Q000097:blood / Q000187:drug effects; D014443:Tyrosine / Q000031:analogs & derivatives / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; C002744:3-nitrotyrosine; D014443:Tyrosine; C477843:bicyclol; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; D000637:Transaminases; D002945:Cisplatin