Abstract
Background:
Cyclophosphamide (Cyc) is an anticancer and immunomodulatory drug, but its use is associated with toxicity, including hepatotoxicity, mediated by oxidative stress (OS), lipid peroxidation, and inflammation. Hence, coadministration of antioxidants probably mitigates Cyc-induced hepatotoxicity.

Aim:
This study assessed the hepatoprotective effect of dipyridamole (Dipyr) against Cyc-induced hepatotoxicity in rats.

Methods:
Thirty-six rats were divided randomly into six equal groups: normal control, Cyc only, Dipyr only (30 mg/kg), Cyc (200 mg/kg) with low-dose Dipyr (15 mg/kg), Cyc with high-dose Dipyr (30 mg/kg), and corn oil (CO) control. Dipyr treatment lasted 10 consecutive days, and Cyc was injected intraperitoneally on day 9. By the end of the study on day 11, body and liver weights, hematological and oxidative stress parameters, liver function biomarkers, NF-κB expression, and histopathology were assessed.

Results:
Cyc administration caused hepatomegaly, reduced body weight, leukocytopenia, elevated serum ALT, AST, and ALP levels, increased malondialdehyde and NF-κB levels, and reduced glutathione, catalase, and total antioxidant capacity. Histopathological examination revealed severe hepatocellular toxicity. Dipyr coadministration mitigated Cyc-induced hepatotoxicity dose-dependently, lowering lipid peroxidation, restoring antioxidant levels, suppressing hepatic NF-κB levels, and mitigating histopathological damage. However, Dipyr failed to restore leukocyte counts.

Conclusion:
These findings confirm Dipyr’s protective potential against Cyc-induced hepatotoxicity mainly via antioxidant and anti-inflammatory mechanisms. Dipyr may probably mitigate hepatic injuries when used as an adjuvant in patients undergoing Cyc therapy.

Key words: Antioxidant; Cyclophosphamide; Dipyridamole; Hepatotoxicity; Oxidative stress.