Sex-specific responses to repeated dose of abamectin in albino rats: a focus on cytotoxicity, genotoxicity, and pro-inflammatory signaling.

Abamectin (AB) is a widely used biopesticide in agricultural and public health applications, and its extensive use has heightened the risk of environmental contamination. Although sex is a critical factor influencing toxicant susceptibility, the mechanisms underlying AB toxicity, particularly the role of sex-related differences, remain largely unexplored. This study investigated the toxicological outcomes of repeated oral exposure to AB (1 mg/kg body weight; 1/10 LD50) for 28 days in male and female Wister albino rats, with an emphasis on sex-dependent responses. Plasma oxidative stress biomarkers, blood cell DNA damage, bone marrow cell mutagenicity, and hepatic inflammatory responses were evaluated. Administration of AB resulted in significant (p ≤ 0.05) lipid peroxidation in both sexes, as evidenced by elevated plasma malondialdehyde (MDA) levels (52.05% in males; 57.40% in females) and a concomitant depletion of total antioxidant capacity (TAC) (24.34% and 30.07% reductions, respectively). This oxidative imbalance was paralleled by a surge in circulating 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, which rose by 137.56% in males and 208.55% in females. Bone marrow toxicity evaluations confirmed pronounced clastogenic and mutagenic effects, reflected by marked elevations in comet assay parameters (tail DNA %, tail length, and tail moment) and micronucleated polychromatic erythrocyte (MN-PCE) frequencies (134.33% in males vs. 214.75% in females). Additionally, AB triggered a robust hepatic inflammatory response, significantly elevating liver tissue levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in males (14.92% and 43.18%, respectively) and females (20.64% and 34.62%, respectively). Notably, female rats exhibited greater overall sensitivity than males across all evaluated endpoints. AB drives oxidative stress-mediated genotoxicity and inflammation in a sex-dependent manner, with females demonstrating heightened susceptibility. These findings emphasize the urgent need to account for sex as a biological variable in pesticide toxicology and warrant further molecular studies to unravel the mechanisms driving differential susceptibility.