Oxidative stress and neuronal dysfunction induced by combined low-dose exposure to abamectin and cypermethrin

Abstract

Background : The increase in agricultural production has been accompanied by intensive pesticide use, leading to chronic environmental contamination. In Togo, residues exceeding regulatory limits have been detected in vegetable crops, particularly abamectin (ABM) and cypermethrin (CYP). ABM, derived from Streptomyces avermitilis, acts on GABA-gated chloride channels and crosses the blood–brain barrier, inducing oxidative stress and neurotoxic damage. CYP, a synthetic pyrethroid, targets voltage-gated sodium channels, resulting in abnormal neuronal discharges and excessive production of reactive oxygen species. While their acute effects are well known, the subchronic impacts of low-dose exposure, especially in combination, remain poorly understood. In this context, the present study aims to evaluate the subchronic neurotoxic effects of combined exposure to abamectin and cypermethrin, administered at realistic doses, in rats. Methods : This study evaluated the subchronic neurotoxicity of ABM and CYP, administered individually or in combination for 90 days to 40 Wistar rats divided into five groups: control, ABM (0.3 mg/kg/day), CYP (0.7 mg/kg/day), mixture M1 (ABM 0.3 + CYP 0.7 mg/kg/day), and mixture M2 (ABM 0.6 + CYP 1.4 mg/kg/day). Results : The results revealed that exposure, particularly to mixtures, decreased brain protein levels, significantly reduced glutathione, superoxide dismutase, and catalase, and markedly increased malondialdehyde levels compared to groups exposed to a single pesticide.. Glutathione S-transferase activity was less affected, but caspase-3 was activated in M1 and M2 groups, indicating apoptosis induction. Histological analyses in M1 and M2 groups showed pronounced hypocellularity associated with cellular hypertrophy and necrotic foci compared with controls. Conclusions : The observed synergistic effect highlights an increased toxicological risk, underscoring the need for further mechanistic studies and appropriate regulatory measures. Under environmental conditions where combined exposures are frequent, these results highlight the importance of considering the impact of mixtures rather than isolated compounds. Keywords: Abamectin, Cypermethrin, Oxidative stress, Pesticide mixture, low-dose