Sex-Specific Cypermethrin Induced Hippocampal Neurotoxicity Is Via the Modulation of Signaling Molecules for Antioxidant Defense, Membrane Integrity, Apoptosis and GABAergic Integrity

Abstract

Pesticides, despite their intended use against pests, can have detrimental effects on non-target organisms, including humans. Its main route of exposure in urban areas is through dietary intake of fruits and vegetables. Oxidative stress, apoptosis and compromise to GABAergic interneurons’ integrity can be attributed to cypermethrin-induced neurotoxicity. The hippocampus, a vital region for memory and learning is particularly susceptible to the neurological toxicity caused by cypermethrin. Sixty adult male and female rats were grouped into control and cypermethrin-treatment groups. The treatment groups received oral dosages of 6.25mg/kg and 12.5mg/kg respectively for fourteen consecutive days. The daily weight was noted. The study was carried out on the hippocampal CA1 and CA3 regions of the rats using biochemical markers: GnRH, Na+/K + ATPase, COX-2, PG-E2 and immunohistochemical markers: Nrf2, CC3, BCL-2, parvalbumin and H&E. Cypermethrin caused a compensatory increase in body weight of the low cypermethrin group and decrease in body weight due to increased dose. Cypermethrin toxicity caused brain weight decrease which was seen more prominently in female high cypermethrin group. Using the biochemical markers, cypermethrin caused neuroinflammation and disrupted the normal functioning of the reproductive hormones and cell membrane; it was more prominent in females. Using the immunohistochemical markers, cypermethrin induced oxidative stress, apoptosis and compromise to the GABAergic interneuron integrity. The female rats expressed higher neuroprotection which can be attributed to estrogen and its signaling pathways. The findings of the study shows that there are dose and sex-specific mechanisms may be involved in cypermethrin neurotoxicity, highlighting the importance of considering sex differences in toxicity studies.