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

摘要

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.