Geraniol Ameliorates Doxorubicin-Mediated Kidney Injury through Alteration of Antioxidant Status, Inflammation, and Apoptosis: Potential Roles of NF-κB and Nrf2/Ho-1

Abstract

Doxorubicin-mediated kidney impairment is a serious problem in cancer treatment. Accordingly, this work investigated the ability of geraniol to modulate doxorubicin-induced kidney damage using a rat model. Rats were randomly assigned to four groups: control, doxorubicin (20 mg/kg, intraperitoneal, i.p.), doxorubicin plus 100 mg/kg of geraniol, and doxorubicin plus 200 mg/kg of geraniol. A single doxorubicin injection triggered kidney impairment, as evidenced by the altered serum creatinine, blood urea nitrogen, and albumin values; it also caused histological changes in the kidney architecture. Additionally, doxorubicin enhanced lipid peroxidation while lowering reduced glutathione, catalase activity, and the expression of glutathione peroxidase and superoxide dismutase. Interestingly, pre-treatment with geraniol rescued doxorubicin-induced alterations in kidney antioxidant parameters, enzymatic activity, and the expression of inflammatory and apoptosis-mediating gene and proteins. Moreover, prophylactic treatment with geraniol preserved most kidney histological characteristics in a dose-dependent manner. These findings support that geraniol could protect against doxorubicin-mediated kidney dysfunction. However, further research is needed to clarify the mechanisms of geraniol’s protective effects against doxorubicin-mediated kidney dysfunction.