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.