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    Protective Effects of Ellagic Acid Against Chemotherapy-Induced Hepatotoxicity
    (2020) Yalçın, Alper; Keleş, Hikmet; Aydın, Hasan; Bozkurt, Mehmet Fatih; Kahraman, Tahir
    Aim: Cyclophosphamide (CP) is a commonly used chemotherapeutic agent despite its toxicadverse effects, including hepatotoxicity. Ellagic acid (EA) is an antioxidant agent and exhibitsfree radical scavenging activities. In this experimental study, the effects of EA on CP-inducedliver injury were investigated.Material and Methods: Twenty-four Sprague-Dawley rats (180-220 gr) were separated intofour equal groups. A single dose of 150 mg/kg CP was given intraperitoneally to generatehepatotoxicity. Different doses (50 and 75 mg/kg) of EA were administered orally 20 minutesbefore, 4 and 8 hours after CP administration. The histopathological evaluation of kidneytissues and immunohistochemical evaluation for caspase-3 were conducted as well as theserum biochemical analyses.Results: CP treated group exhibited a significant increase in serum hepatic enzymes, aspartateaminotransferase (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 significantincrease. 75 mg/kg EA treatment caused a non-significant elevation in total cholesterol (TC)concentration. Microscopic analysis showed a significant congestion, edema, degeneration andnecrosis in the livers of CP administered group. However, edema, degeneration, and necrosiswere significantly reduced in animals treated with EA-75. In addition, caspase-3 expressionsignificantly decreased in EA-75 group.Conclusion: These results indicate the protective effects of EA in CP-induced hepatotoxicity in rats.