Fipronil induced oxidative stress involves alterations in SOD1 and catalase gene expression in male mice liver: Protection by vitamins E and C.
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.
['Badgujar|Prarabdh C|PC|', 'Chandratre|Gauri A|GA|', 'Pawar|Nitin N|NN|', 'Telang|A G|AG|', 'Kurade|N P|NP|']
D000410:Alanine Transaminase D000818:Animals D000975:Antioxidants D001205:Ascorbic Acid D001219:Aspartate Aminotransferases D001835:Body Weight D002374:Catalase D015536:Down-Regulation D015870:Gene Expression D005978:Glutathione D005982:Glutathione Transferase D015227:Lipid Peroxidation D008099:Liver D008297:Male D051379:Mice D018384:Oxidative Stress D020011:Protective Agents D011720:Pyrazoles D012333:RNA, Messenger D000072105:Superoxide Dismutase-1 D014810:Vitamin E
fipronil oxidative stress liver vitamin E mRNA expression histopathology vitamin C