Docetaxel (DTX) is a frequently used antineoplastic agent despite its dose-limiting toxic effects. Our objective was to assess the effects of oleuropein (OLE), a natural polyphenol, on DTX-induced toxicity. Thirty-two male rats were randomly assigned to four groups for a four-week treatment: Control (sham), DTX (5 mg/kg weekly, i.p.), OLE (30 mg/kg daily, p.o.), and DTX+OLE. Biochemical and gene expression analyses were performed on liver, kidney, and blood samples. Additionally, histological and immunohistochemical evaluations were conducted on the liver and kidneys. OLE reduced the DTX-induced oxidative stress index in tissues. In contrast to DTX, it decreased caspase-3 and Bax gene expressions while increasing Bcl-2 expression. Furthermore, OLE improved the ALT, AST, urea, and creatinine levels, which were impaired by DTX administration. It also reduced serum IL-6, IL-1β, and TNF-α levels, which had been elevated due to DTX. Histopathological and immunohistochemical examinations revealed that OLE administration mitigated DTX-related damage in both tissues. These findings suggest that OLE might offer protection against DTX-induced liver and kidney toxicity in rats.

Abstract: Docetaxel (Dtx) is a frequently used antineoplastic agent despite its dose-limiting toxic effects. Our objective was to assess the effects of oleuropein (Ole), a natural polyphenol, on Dtx-induced toxicity. Thirty-two male rats were randomly assigned to four groups for a four-week treatment: Control (sham), Dtx (5 mg/kg weekly, i.p.), Ole (30 mg/kg daily, p.o.), and Dtx+Ole. Biochemical and gene expression analyses were performed on liver, kidney, and blood samples. Additionally, histological and immunohistochemical evaluations were conducted on the liver and kidneys. Ole reduced the Dtx-induced oxidative stress index in tissues. In contrast to Dtx, it decreased caspase-3 and Bax gene expressions while increasing Bcl-2 expression. Furthermore, Ole improved the ALT, AST, urea, and creatinine levels, which were impaired by Dtx administration. It also reduced serum IL-6, IL-1β, and TNF-α levels, which had been elevated due to Dtx. Histopathological and immunohistochemical examinations revealed that Ole administration mitigated Dtx-related damage in both tissues. These findings suggest that Ole might offer protection against Dtx-induced liver and kidney toxicity in rats.Keywords : Docetaxel, oleuropein, oxidative stress, hepatotoxicity, nephrotoxicity.