Gender-specific oxidative and neurotoxic effects of imidacloprid modulated by piperonyl butoxide and menadione in the kidney of Sprague-Dawley rats

Because of its negative impact on non-target organisms, neonicotinoid insecticide imidacloprid application is debated recently. Gender- and duration-dependent oxidative stress and neurotoxicity potential of imidacloprid which modulated by piperonyl butoxide, a cytochrome P450 inhibitor and menadione, an aldehyde oxidase inhibitor were investigated in the kidney of Sprague-Dawley rats in the present study. For this purpose, imidacloprid, piperonyl butoxide and menadione were injected intraperitoneally. Renal total glutathione, thiobarbituric acid reactive substances and protein contents and glutathione peroxidase, glutathione S-transferase, catalase and total cholinesterase enzyme activities were measured spectrophotometrically 12- and 24-h after administration.Imidacloprid in both sexes did not make any impact at 12-h. Total glutathione content, lipid peroxidation and total cholinesterase activity increased, while protein content was decreased in male rats at 24-h. Glutathione S-transferase activity increased in females at the same duration. Imidacloprid after piperonyl butoxide injection caused a decrease in lipid peroxidation and an increase in total cholinesterase activity in males. Decreased lipid peroxidation by piperonyl butoxide reached to control levels after imidacloprid injection in females. Piperonyl butoxide led to a further increase in imidacloprid induced glutathione S-transferase activity. Menadione as a redox-active compound caused an increase in catalase activity and total glutathione content and a decrease in protein content in male rats. Both of menadione and imidacloprid led to decrease in protein content and to increase in total glutathione concentration while an improvement was observed in their combined effects in males. Moreover, glutathione peroxidase activity and lipid peroxidation levels decreased.It was thought that gender-dependent oxidative and neurotoxic potential of imidacloprid originated from gender-specific active transport systems that are allowed to imidacloprid entry to the cell and cytochrome P450 and aldehyde oxidase enzyme systems which are more actively metabolized imidacloprid in males than females. Imidacloprid-related oxidative effects may be dependent to Ca2+ entry to the cell from the nicotinic acetylcholine receptor activation and increase in total cholinesterase activity is an adaptive response to the receptor activation caused by imidacloprid. Decreased lipid peroxidation levels by piperonyl butoxide pre-treatment could be dependent to elevated catalase and total cholinesterase activities in males. Piperonyl butoxide increased imidacloprid-induced glutathione S-transferase activity in females, and then glutathione conjugation of imidacloprid metabolites generated from other metabolic processes than cytochrome P450 should be investigated. Attenuation was observed in imidacloprid and menadione toxicities which could be related with decreased aldehyde oxidase catalysed imidacloprid metabolite formation. Menadione co-treatment is beneficial to determine the imidacloprid toxicity in females.