Carvacrol alleviates hepatorenal apoptosis in rats following exposure to lambda-cyhalothrin by targeting the Trx1/Prx1/Bcl2 pathway: <i>in vivo</i> and molecular docking studies

Lambda-cyhalothrin (LCT), a type II pyrethroid, is known to cause several side effects, including hepatorenal toxicity, despite its widespread use. This study investigates the protective effect of carvacrol (CVR) against LCT-induced oxidative stress, inflammation, and apoptotic pathway in the liver and kidney. Forty-eight male Sprague-Dawley rats were randomly assigned to eight groups; the first two groups served as controls (negative and CVR). The third, fourth, and fifth groups received LCT at doses of 2, 4, and 8 mg/kg/day via gavage. The sixth, seventh, and eighth groups received a dose of CVR (50 mg/kg/day) during LCT exposure for 90 days. Co-treatment with CVR reduced the elevated levels of hepatic biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT)), kidney markers (urea and creatinine), and various histopathological changes caused by LCT exposure. Additionally, CVR mitigated LCT-induced oxidative stress by lowering malondialdehyde (MDA) levels, increasing cellular antioxidant (glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR)), and upregulating the transcription of the Trx1 and Prx1 genes. Moreover, CVR decreased the pro-inflammatory cytokine (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) levels, along with the activation of apoptotic markers (p53, Bax, and caspase-3), and lowered Bcl2 levels. Furthermore, the <i>in silico</i> study confirmed that LCT interacts directly with the active cysteine residues of Trx1, Prx1, and Bcl2 proteins at high binding energies. In conclusion, sub-chronic exposure to LCT can induce hepatorenal apoptosis by inhibiting the Trx1/Prx1/Bcl2 pathway, an effect that is reversed by CVR's antioxidant properties.