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.
Keywords: Caspase-3; cyclophosphamide; ellagic acid; hepatotoxicity; lipids.