Apoptosis and Cell Cycle Dysregulation in Ampligo® 150 ZC-Induced Nephrotoxicity in Female Rabbits: Protective Effects of Thymus vulgaris Essential Oil and Vitamin C.

The widespread use of modern insecticide formulations underscores the need for mechanistic evaluation of their potential renal toxicity. This study investigated the nephrotoxic effects of Ampligo® 150 ZC, a binary formulation of lambda-cyhalothrin and chlorantraniliprole, in female rabbits under subacute exposure conditions, with particular emphasis on apoptosis-related and epithelial integrity biomarkers, and evaluated the protective effects of thyme essential oil (TEO) and vitamin C. Rabbits were allocated into four groups: control, AP, AP + TEO, and AP + TEO + vitamin C. Ampligo (AP) exposure resulted in significant renal dysfunction, as evidenced by elevated biochemical biomarkers and marked histopathological lesions. At the molecular level, AP induced p53 upregulation alongside Bcl-2 and Cyclin D1 downregulation, suggesting apoptosis induction and cell cycle dysregulation. Moreover, reduced E-cadherin and β-catenin expressions indicated disruption of epithelial junction integrity and impaired renal structural homeostasis. Notably, co-administration of TEO and vitamin C markedly attenuated these alterations, improving biochemical, histopathological, and immunohistochemical parameters. Overall, these findings suggest that AP-driven nephrotoxicity may involve apoptotic and epithelial pathways under subacute exposure conditions, whereas antioxidant co-treatment may mitigate kidney injury, supporting the potential of natural antioxidants as adjuncts against pesticide-induced renal injury.