Gauri A. Chandratre

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.

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.

Histopathological alterations induced by subacute fipronil toxicity in mice and its amelioration by combination of α-tocopherol and ascorbic acid

Swiss albino female mice were randomly divided into four equal groups comprising 6 animals in each. Group 1 was administered vehicle, corn oil and served as control. Group 2 mice received fipronil @ 10 mg/kg body weight; mice in the group 3 were administered with combination of α-tocopherol and ascorbic acid, each @ 100 mg/kg body weight. Mice of group 4 were treated with α-tocopherol and ascorbic acid, each @ 100 mg/kg body weight, 2 hours before administration of fipronil @ 10 mg/kg body weight. Dosage were administered orally daily by gavage for consecutive 28 days. Mice were sacrificed at the end of 28 days to study gross and histopathological alterations. Grossly, liver of mice treated with fipronil was fragile with change of consistency and showed scattered pale foci. In histopathology, liver of mice treated with fipronil showed severe degenerative changes in heptocytes with presence of large number of necrotic foci, infiltration of mononuclear cells and congestion. In kidney, severe degenerative changes along with necrosis of tubular lining cells and congestion were evident in the fipronil treated mice. Severe emphysema and rupture of alveoli along with congestion was observed in the lung of mice treated with fipronil. Testis also showed depopulation of germs cells and thickening in basal layer of seminiferous tubules in fipronil treated mice. Co-administration of combination of these two vitamins against fipronil restored gross and histological changes in these organs. This study indicated that, subacute exposure of fipronil @ 10 mg/kg bw results in heaptotoxicity and cytotoxicity. Combined administration of antioxidant vitmains exerted protective action and ameliorated histological architecture of major organs.