Salvia officinalis aqueous extract mitigates abamectin-induced testicular dysfunction in rats by targeting oxidative stress, mitochondrial fusion proteins, and key apoptotic regulators.

Abamectin (ABM) is a macrocyclic lactone insecticide that induces oxidative stress and testicular toxicity, but its specific effects on male reproductive function remain unclear. Here, we tested whether an aqueous extract of Salvia officinalis (S. officinalis) could mitigate ABM-induced testicular injury in adult male rats, focusing on mitochondrial fusion and apoptosis. Thirty-six rats were divided into six groups: control, S. officinalis extract (100 mg/kg), low-dose ABM (0.5 mg/kg), high-dose ABM (1 mg/kg), S. officinalis + low-dose ABM, and S. officinalis + high-dose ABM, for 70 days. Our results showed that the extract was rich in total phenolics and flavonoids. The main phenolic compounds were ferulic acid, syringic acid, caffeic acid, p-coumaric acid, and α-tocopherol, while the main flavonoids were luteolin, 2'-hydroxyflavone, apigenin, and quercetin. Rats exposed to ABM had lower sperm concentration and motility, more abnormal sperm, and markedly lower serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone in a dose-dependent manner. Furthermore, testicular malondialdehyde and nitric oxide levels increased, whereas catalase activity, glutathione levels, and the activities of superoxide dismutase and glutathione S-transferase decreased. Gene expression analysis showed reduced mitofusin-1 and mitofusin-2 and increased p53 and caspase-9 expression. Notably, co-administration of S. officinalis with ABM improved sperm quality, hormone levels, antioxidant status, gene expression, and testicular tissue structure. Our findings highlight the protective mechanisms of S. officinalis, including enhancing antioxidant defenses, promoting mitochondrial fusion, and inhibiting the intrinsic apoptotic pathway. These results suggest that the S. officinalis extract could have therapeutic potential for ABM-induced male reproductive toxicity.