Caffeic acid phenethyl ester (CAPE) ameliorates cisplatin-induced hepatotoxicity in rabbit.
In this study, it was aimed to investigate the protective effect of caffeic acid phenethyl ester (CAPE) on cisplatin hepatotoxicity. Thirty New Zealand rabbits were divided into 5 groups as group 1 (saline-injected control, C), group 2 (1% ethanol; vehicle for CAPE, E), group 3 (CAPE), group 4 (cisplatin, CS) and group 5 (cisplatin plus CAPE, CS+CAPE). Cisplatin caused increased immunoreactivity against inducible nitric oxide synthase (iNOS), but CAPE treatment reduced the immunoreactive hepatocytes. Liver malondialdehide (MDA), nitric oxide (NO(.)) levels and xanthine oxidase (XO) activities were higher in CS than in groups C and E. Cisplatin treatment also significantly decreased the tissue reduced glutathione (GSH) concentration compared to groups C and E. CAPE administration normalized the tissue GSH level and XO activity in group CS+CAPE, whereas CAPE treatment did not affect MDA level in group CS+CAPE. In addition, CAPE treatment significantly depressed the cisplatin-induced NO(.) increase in group CS+CAPE. Histopathologically, cisplatin caused hydropic degenerations, necrosis in hepatocytes, sinusoidal congestion, Kupffer cell proliferation and mononuclear cell infiltration. These alterations were less severe in rabbits receiving CS+CAPE. Parallel to histopathology, cisplatin increased serum AST and ALT levels, whereas CAPE treatment significantly reduced cisplatin-induced AST and ALT rise in the serum. Results suggest that cisplatin causes oxidative and nitrosative damage to hepatocytes. Cisplatin-induced increase in XO and NO(.) could contribute oxidative stress in the hepatotoxicity. CAPE shows partial protection against cisplatin-associated biochemical and histopathological alterations.
Kart
Asim
A
Department of Pharmacology and Toxicology, College of Veterinary Medicine, Kafkas University, 36100 Kars, Turkey. asimkart@hotmail.com
Cigremis
Yilmaz
Y
Karaman
Musa
M
Ozen
Hasan
H
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002109:Caffeic Acids / Q000494:pharmacology*; D002945:Cisplatin / Q000506:poisoning*; D005978:Glutathione / Q000032:analysis; D008099:Liver / Q000033:anatomy & histology / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D020556:Neutrophil Infiltration / Q000187:drug effects; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D014969:Xanthine Oxidase / Q000032:analysis
D002109:Caffeic Acids; D009569:Nitric Oxide; D008315:Malondialdehyde; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C055494:caffeic acid phenethyl ester; D005978:Glutathione; D010626:Phenylethyl Alcohol; D002945:Cisplatin