Neurotoxic Effect of Fipronil in Male Wistar Rats: Ameliorative Effect of L-Arginine and L-Carnitine

SIMPLE SUMMARY: Insecticides are widely used in agricultural and household environments. They induce wide range of deleterious effects. Fipronil is one of the most widely used phenylpyrazoles insecticides. The neurotoxic effect of such insecticide was tested in the present study with special emphasis on cognitive deficit as well as testing the possible ameliorative impacts of L-arginine and L-carnitine. The study proposed fipronil-induced cognitive deficit as a reflection to oxidative stress and neuro-inflammation. Moreover, L-arginine and L-carnitine exerted ameliorative influence on fipronil induced oxidative stress and neuro-inflammation. Therefore, L-arginine and L-carnitine can be considered as prospective candidates for mitigation of pesticide induced neurotoxicity especially in people with high-risk exposure to pesticide. ABSTRACT: The ameliorative effect of L-arginine (LA) and L-carnitine (LC) against fipronil (FPN)-induced neurotoxicity was explored. In this case, 36 adult male rats were randomly divided into six groups: group I received distilled water, group II received 500 mg/kg LA, group III received 100 mg/kg LC, group IV received 4.85 mg/kg FPN, group V received 4.85 mg/kg FPN and 500 mg/kg LA and group VI received 4.85 mg/kg FPN and 100 mg/kg LC for 6 weeks. Cognitive performance was assessed using Barnes maze (BM). Serum corticosterone, brain total antioxidant capacity (TAC), malondialdehyde (MDA) and dopamine were measured. Histopathology and immunohistochemistry of ionized calcium-binding adaptor (Iba-1), doublecortin (DCX) and serotonin (S-2A) receptors were performed. Fipronil induced noticeable deterioration in spatial learning and memory performance. In addition, FPN significantly (p < 0.05) diminished brain antioxidant defense system and dopamine coincide with elevated serum corticosterone level. Histopathological examination revealed degenerative and necrotic changes. Furthermore, Iba-1 and DCX were significantly expressed in cortex and hippocampus whereas S-2A receptors were significantly lowered in FPN group. However, administration of LA or LC alleviated FPN-induced deteriorations. In conclusion, LA and LC could be prospective candidates for mitigation of FPN-induced neurotoxicity via their antioxidant, anti-inflammatory and neuropotentiating effects.