Spinosin-carvacrol co-treatment attenuates deltamethrin-induced hepatotoxicity via modulation of oxidative stress, inflammation, and apoptosis in mice.

Exposure to certain pesticides remains a significant environmental and public health concern due to their capacity to induce oxidative damage in vital organs. Deltamethrin (DEL), a widely used synthetic pyrethroid, disrupts hepatic function primarily through oxidative stress-mediated mechanisms. This study investigated the protective effects of spinosin (SP) and carvacrol (CAR), administered individually or in combination, against DEL-induced liver toxicity and explored the underlying molecular pathways. Hepatic injury was induced in male Swiss albino mice by oral gavage of DEL (15 mg/kg bw). SP and CAR were administered at 50 mg/kg bw, either alone or in combination, while silymarin (50 mg/kg bw) served as a reference compound. All treatments were administered once daily for 28 consecutive days. DEL exposure significantly reduced SOD, CAT, GSH, and PGE2 levels, accompanied by downregulation of HO-1, Nrf2, and Bcl-2 expression. Conversely, levels of ALP, ALT, AST, MDA, NO, TNF-α, IL-1β, IL-6, Bax, and Cas-3 were significantly increased. Treatment with SP and CAR ameliorated these alterations, with combined administration demonstrating greater efficacy than monotherapy. Overall, the findings suggest that SP and CAR co-treatment may exert enhanced hepatoprotective effects, potentially through coordinated regulation of oxidative stress, inflammation, apoptosis, and activation of the Nrf2/HO-1 signaling pathway.