Acetaminophen-Induced Nephrotoxicity: Oxidative Stress and Renal Function Impairment in Wistar Rats

Abstract

Introduction: Acetaminophen (APAP) is a widely used analgesic, but its potential for extrahepatic toxicity, particularly nephrotoxicity, remains a concern.

Aim: To evaluate the dose-dependent nephrotoxic effects of APAP on renal function and oxidative stress biomarkers in Wistar rats.

Methods: 20 Male Wistar rats weighing 150 - 200g divided into four groups, were administered APAP at three doses (100, 200, and 300 mg/kg bw). Biochemical analyses measured oxidative stress markers—malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT)—and renal function indicators (serum creatinine and blood urea nitrogen, BUN). Histopathological examination of kidney tissues was also conducted.

Results: APAP administration induced a significant, dose-dependent increase in MDA levels, indicating elevated lipid peroxidation. Concurrently, antioxidant enzymes (SOD, GSH, CAT) were significantly depleted. Renal function was impaired, evidenced by dose-dependent elevations in serum creatinine and BUN. Histopathological analysis confirmed progressive glomerular damage and vascular congestion correlating with higher APAP doses.

Conclusion: APAP-induced nephrotoxicity is mediated through oxidative stress, characterized by increased lipid peroxidation and antioxidant depletion, leading to renal structural and functional impairment. These findings underscore the need for cautious APAP use and further research into protective strategies against renal damage.