title: The effects of acute acetaminophen toxicity on hepatic mRNA expression of SOD, CAT, GSH-Px, and levels of peroxynitrite, nitric oxide, reduced glutathione, and malondialdehyde in rabbit.
abstract: We investigated the regulation of antioxidant system under acetaminophen (AAP) toxicity. Twelve male New Zealand rabbits were divided into two groups with the following treatments: Group 1 animals were intraperitoneally injected with single saline (control). Group 2 animals were treated with intraperitoneal injection of AAP at a dose of 250 mg/kg body weight. Four hours following the treatments, blood samples were collected and the rabbits were sacrificed to collect liver samples. Hepatocellular damage was evaluated by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as histopathological examinations and immunohistochemical analysis. Tissue-reduced glutathione (GSH), nitric oxide (NO(.)), and malondialdehyde (MDA) levels were also measured. mRNA expression levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) were measured by semi-quantitative RT-PCR. It was found that liver GSH was reduced significantly in AAP-treated rabbits (P < 0.05), while MDA and NO(.) levels were increased when they were compared to control (P < 0.05). Blood AST and ALT levels were also increased following AAP treatment (P < 0.05). Hepatocellular degeneration and severe necrosis were detected in histopathological examinations. Increased immunostaining was observed for inducible nitric oxide synthase (iNOS) and nitrotyrosine in the liver. There were no changes in mRNA expression levels of SOD, CAT, and GSH-Px after AAP treatment compared to control group. These results suggest that the expression of these enzymes, which are involved in the antioxidant system, may not be altered after AAP toxicity, although classical toxic changes such as depletion of GSH, hepatocellular necrosis, and increased immunostaining for iNOS and nitrotyrosine were detected.
authors.affiliation: Department of Biology, Faculty of Science and Arts, Kafkas University, 36100, Kars, Turkey. yilmazcigremis@hotmail.com
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Cigremis
authors.forename: Huseyin
authors.initials: H
authors.lastname: Turel
authors.forename: Kevser
authors.initials: K
authors.lastname: Adiguzel
authors.forename: Muslum
authors.initials: M
authors.lastname: Akgoz
authors.forename: Asim
authors.initials: A
authors.lastname: Kart
authors.forename: Musa
authors.initials: M
authors.lastname: Karaman
authors.forename: Hasan
authors.initials: H
authors.lastname: Ozen
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D011817:Rabbits; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
chemical_list: D009573:Nitrites; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D000082:Acetaminophen; D008315:Malondialdehyde; D012313:RNA; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione