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Effects of Hydroxytyrosol Against Doxorubicin-Induced Hepatotoxicity Through Alterations in Dardarin and Podocalyxin
Elif Onat1, Nevin Kocaman2, Erkan Yilmaz3
1Department of Pharmacology, Adıyaman University, Adıyaman, TUR.
Introduction:
This study investigated whether dardarin (LRRK2) and podocalyxin (PODX) contribute to the hepatoprotective effects of hydroxytyrosol (HT) against doxorubicin (DOX)-induced liver injury in rats.
Methods:
Twenty-eight female Sprague Dawley rats were randomly assigned to four groups: Control, HT, DOX, and DOX+HT. DOX (10 mg/kg) was administered intraperitoneally as a single dose on day 1. HT was given orally at 100 mg/kg/day for 28 days. In the DOX+HT group, animals received DOX on day 1 followed by daily oral HT for 28 days. At the end of the experiment, liver tissues were collected for histopathological evaluation, and all findings were statistically analyzed.
Results:
Histopathological assessments showed significantly elevated LRRK2 and PODX expression levels in the DOX group, while co-treatment with HT markedly reduced these increases (p<0.001). Additionally, DOX-induced hepatic fibrosis, leukocyte infiltration, congestion, and sinusoidal dilatation were substantially alleviated in the DOX+HT group (p<0.001).
Conclusion:
HT demonstrated beneficial effects on histopathological and immunohistochemical changes in DOX-induced liver injury. The reduction in LRRK2 and PODX expression implies that these molecules may be involved in the mechanisms underlying HT-mediated hepatoprotection. These findings highlight the potential therapeutic value of HT in mitigating DOX-associated hepatotoxicity.