Protective effects of ellagic acid against chemotherapy-induced hepatotoxicity

Abstract

Aim: Cyclophosphamide (CP) is a commonly used chemotherapeutic agent despite its toxic adverse effects, including hepatotoxicity. Ellagic acid (EA) is an antioxidant agent and exhibits free radical scavenging activities. In this experimental study, the effects of EA on CP-induced liver injury were investigated. Material and Methods: Twenty-four Sprague-Dawley rats (180-220 gr) were separated into four equal groups. A single dose of 150 mg/kg CP was given intraperitoneally to generate hepatotoxicity. Different doses (50 and 75 mg/kg) of EA were administered orally 20 minutes before, 4 and 8 hours after CP administration. The histopathological evaluation of kidney tissues and immunohistochemical evaluation for caspase-3 were conducted as well as the serum biochemical analyses. Results: CP treated group exhibited a significant increase in serum hepatic enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), compared to the control group. Similarly, the total triglycerides (TG) and very-low-density lipoprotein cholesterol (VLDL-C) levels increased significantly. Additionally, the high-density lipoprotein cholesterol (HDL-C) levels decreased, which was not significant, compared to the control group. At both EA doses, VLDL-C, AST, ALT levels decreased significantly while HDL-C level revealed a significant increase. 75 mg/kg EA treatment caused a non-significant elevation in total cholesterol (TC) concentration. Microscopic analysis showed a significant congestion, edema, degeneration and necrosis in the livers of CP administered group. However, edema, degeneration, and necrosis were significantly reduced in animals treated with EA-75. In addition, caspase-3 expression significantly decreased in EA-75 group. Conclusion: These results indicate the protective effects of EA in CP-induced hepatotoxicity in rats.