Hepatoprotective effect of date palm fruit extract against doxorubicin intoxication in Wistar rats: In vivo and in silico studies

Objective: To investigate the prophylactic efficacy of date palm fruit extract against doxorubicin-induced hepatotoxicity in Wistar albino rats. Methods: The rats were equally and randomly assigned to 6 groups: group 1 (untreated control), group 2 and 3 given daily oral administration of prophylactic aqueous extract of date palm fruit at 0.75 and 1.5 mg/kg body weight, respectively, and group 4, 5 and 6 intraperitoneally injected with doxorubicin at 15 mg/kg on day 30. Rats in group 5 and 6 received daily oral administration of aqueous extract of date palm fruit at 0.75 and 1.5 mg/kg body weight, respectively, for 30 d. The phytochemicals identified by GC-MS analysis were analyzed using in silico study. Antioxidant enzymes, liver enzymatic, biochemical parameters and histopathological analysis were determined to evaluate hepatoprotective activity of date extract. Results: Aqueous extract of date palm fruit significantly mitigated doxorubicin-induced changes in activities of liver enzymes, reduced reactive oxygen species levels, and suppressed lipid peroxidation and DNA damage. Moreover, aqueous extract of date palm fruit reduced doxorubicin-induced hepatic lesions. Molecular docking studies showed that most compounds of aqueous extract of date palm fruit identified via GC-MS had good interaction with proteins of human pregnane X receptor, oxygenase-1, and CYP2C9. Conclusions: The aqueous extract of date palm fruit mitigates doxorubicin-mediated DNA damage and hepatotoxicity, and restores normal liver function and may be a promising agent against the deleterious effects of doxorubicin.