title: Fipronil induced oxidative stress involves alterations in SOD1 and catalase gene expression in male mice liver: Protection by vitamins E and C.
abstract: In the present investigation, hepatic oxidative stress induced by fipronil was evaluated in male mice. We also investigated whether pretreatment with antioxidant vitamins E and C could protect mice against these effects. Several studies conducted in cell lines have shown fipronil as a potent oxidant; however, no information is available regarding its oxidative stress inducing potential in an animal model. Out of 8 mice groups, fipronil was administered to three groups at low, medium, and high dose based on its oral LD50 (2.5, 5, and 10 mg/kg). All three doses of fipronil caused a significant increase in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level with concomitant increase in the absolute and relative weight of liver. High dose of fipronil caused significant down-regulation in the hepatic mRNA expression of superoxide dismutase 1 (SOD1) and catalase (0.412 ± 0.01 and 0.376 ± 0.05-fold, respectively) as well as an increase in the lipid peroxidation (LPO). Also, decrease in the activity of antioxidant enzymes; SOD, catalase, and glutathione-S-transferase (GST) and the content of nonantioxidant enzymes; glutathione and total thiol were recorded. Histopathological examination of liver revealed dose dependant changes such as severe fatty degeneration and vacuolation leading to hepatocellular necrosis. Prior administration of vitamin E or vitamin C against fipronil high dose caused decrease in lipid peroxidation and increased activity of antioxidant enzymes. Severe reduction observed in functional activities of antioxidant enzymes was aptly substantiated by down-regulation seen in their relative mRNA expression. Thus results of the present study imply that liver is an important target organ for fipronil and similar to in vitro reports, it induces oxidative stress in the mice liver, which in turn could be responsible for its hepatotoxic nature. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1147-1158, 2016.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243 122, India.
authors.forename: Prarabdh C
authors.initials: PC
authors.lastname: Badgujar
authors.affiliation: Division of Pathology, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243 122, India.
authors.forename: Gauri A
authors.initials: GA
authors.lastname: Chandratre
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243 122, India.
authors.forename: Nitin N
authors.initials: NN
authors.lastname: Pawar
authors.affiliation: Toxicology Laboratory, Centre for Animal Disease Research and Diagnosis, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243 122, India.
authors.forename: A G
authors.initials: AG
authors.lastname: Telang
authors.affiliation: Division of Pathology, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243 122, India.
authors.forename: N P
authors.initials: NP
authors.lastname: Kurade
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology; D011720:Pyrazoles / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D020011:Protective Agents; D011720:Pyrazoles; D012333:RNA, Messenger; D014810:Vitamin E; D002374:Catalase; D000072105:Superoxide Dismutase-1; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D001205:Ascorbic Acid; C082360:fipronil
keywords: fipronil; histopathology; liver; mRNA expression; oxidative stress; vitamin C; vitamin E