Protective effects of N-acetyl-l-cysteine against penconazole-triggered hepatorenal toxicity in adult rats.

Introduction: Penconazole (PEN) is a widely applied triazole fungicide. This study sought to define the efficacy of N-acetyl-l-cysteine (NAC) in mitigating PEN-triggered hepatorenal toxicity in rats.

Material and methods: Twenty-eight adult male albino Wistar rats were assigned to four groups: a normal control (NC), a PEN group, a NAC group and a PEN+NAC group. Administration of PEN (50 mg/kg body weight (b.w.) every 2 days) and NAC (150 mg/kg b.w., daily) took place via oral gavage for 10 days.

Results: Effective amelioration by NAC of PEN-induced liver and kidney dysfunction was indicated by a significant reduction in the circulating liver and kidney markers (aspartate aminotransferase, alanine aminotransferase, urea and creatinine). Attenuation of PEN-induced oxidative stress and lipid peroxidation in liver and kidney tissues was evident in a significant reduction in malondialdehyde and enhanced total antioxidant capacity. Moreover, NAC significantly reduced the histopathological alterations and the expression of tumour necrosis factor α in liver and kidney tissue. Furthermore, NAC maintained the messenger RNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase 1, and Kelch-like erythroid cell-derived protein 1 and prevented nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein upregulation caused by PEN.

Conclusion: N-acetyl-1-cysteine protected against PEN-induced hepatorenal oxidative damage and inflammatory response via activation of Nrf2 and inhibition of NF-κB pathways.