Akademik Veri Yönetim Sistemi
Chemico-biological interactions, cilt.365, ss.110111, 2022 (SCI-Expanded)
Doxorubicin (DOX) is an antitumor drug that is powerful but can cause worse outcomes, including nephrotoxicity, and therefore has limited clinical use. Therefore, it is necessary to identify safer agents that can minimize the damage caused by the drug without shifting the treatment performance, in addition to clarifying the underlying mechanisms of DOX-induced aberrant in vivo renal activation. In this study, we tested the prophylactic capacity and mechanisms of action of tannic acid (TA) against DOX-mediated kidney damage in rats and evaluated the nephrotoxic activity of DOX when used with TA. Rats were treated during the two weeks with cumulative (18 mg/kg with six different injections) DOX, daily TA (50 mg/kg), and the DOX + TA combination. Changes in major metabolites and components involved in antioxidant metabolism were evaluated in the kidney tissues of all animals. Further, the gene expression levels of regulatory factors that have critical importance in cell metabolism, inflammation, and apoptosis were investigated. Both biochemical and molecular examinations showed that TA improved DOX-induced dysregulations at both protein and gene levels in the kidneys. Increased lipid peroxidation and decreased glutathione levels were reversed. Consistent with oxidative stress marker metabolites, suppressed antioxidant enzyme activities and transcript levels of antioxidant system members were restored. Of note, combination treatment with TA could overcome doxorubicin-induced gene expressions markedly altered by DOX, suggesting that nephroprotection conferred by TA involved the remodeling of stress resistance, cell metabolism, inflammation, and apoptosis. Collectively, the present in vivo study suggests that TA could be used as a multitarget and effective agent for the mitigation of doxorubicin-induced nephrotoxicity without changing the therapeutic efficacy of the drug.