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.

Fipronil induced oxidative stress in kidney and brain of mice: protective effect of vitamin E and vitamin C.

Fipronil is a relatively new insecticide of the phenpyrazole group. Fipronil-induced effects on antioxidant system and oxidative stress biomarkers are yet to be studied in vivo. The present study was undertaken to evaluate fipronil-induced alterations in the blood biochemical markers and tissue antioxidant enzymes after oral exposure in mice and to explore possible protective effect of pre-treatment of antioxidant vitamins against these alterations. Mice were divided into eight groups containing control, test and amelioration groups. Mice in the test groups were exposed to different doses of fipronil, i.e., 2.5, 5 and 10 mg/kg bw, respectively for 28 days. Mice in the amelioration groups were treated with vitamin E or vitamin C (each at 100 mg/kg) 2 h prior to high dose (10 mg/kg) of fipronil. Fipronil exposure at three doses caused significant increase in the blood biochemical markers, lipid peroxidation and prominent histopathological alterations; while level of antioxidant enzymes was severely decreased both in kidney and brain tissues. Prior administration of vitamin E or vitamin C in the fipronil exposed mice led to decrease in lipid peroxidation and significant increase in activities of antioxidants, viz., glutathione, total thiol, superoxide dismutase and catalase. Vitamin E and vitamin C administration in fipronil exposed mice also improved histological architecture of the kidney and brain when compared with fipronil alone treated groups. Thus, results of the present study demonstrated that in vivo fipronil exposure induces oxidative stress and pre-treatment with vitamin E or C can protect mice against this oxidative insult.