Department of Molecular Biology and Genetics, Faculty of Science, Atatürk University, Erzurum, Türkiye.
Department of Pharmacy Services, Nihat Delibalta Gole Vocational High School, Ardahan University, Ardahan, Türkiye.
J Biochem Mol Toxicol. 2024 Aug;38(8):e23798. doi: 10.1002/jbt.23798.
Doxorubicin (DOX), which is frequently used in cancer treatment, has limited clinical use due to adverse effects on healthy tissues, especially the liver. Therefore, it is necessary to research the molecular basis of DOX-induced organ and tissue damage and protective agents. In this study, we aimed to examine the protective effects of tannic acid (TA) against DOX-induced hepatoxicity in experimental rat models. Rats were randomly divided into four experimental groups: the untreated control, DOX, TA, and cotreatment (DOX + TA) groups. We investigated the antioxidant system's main components and oxidative stress indicators. Moreover, we examined alterations in the mRNA expression of critical regulators that modulate apoptosis, inflammation, and cell metabolism to better understand the underlying factors of DOX-induced liver toxicity. The results showed that DOX exposure caused an increase in MDA levels and a significant depletion of GSH content in rat liver tissues. Consistent with oxidative stress-related metabolites, DOX was found to significantly suppress both mRNA expression and enzyme activities of antioxidant system components. Moreover, DOX exposure had significant adverse effects on regulating the other regulatory genes studied. However, it was determined that TA could alleviate many of the negative changes caused by DOX. The results of the present study indicated that TA might be considered a versatile candidate that could prevent DOX-induced hepatotoxicity, possibly by preserving cell physiology, viability, and especially redox balance.
多柔比星（DOX）是一种常用于癌症治疗的药物，但由于其对健康组织（尤其是肝脏）的不良反应，临床应用受到限制。因此，有必要研究 DOX 诱导的器官和组织损伤的分子基础以及保护剂。在本研究中，我们旨在研究鞣酸（TA）对 DOX 诱导的实验大鼠模型肝毒性的保护作用。大鼠随机分为四组：未处理对照组、DOX 组、TA 组和联合治疗组（DOX+TA 组）。我们研究了抗氧化系统主要成分和氧化应激指标的变化。此外，我们还检测了调节细胞凋亡、炎症和细胞代谢的关键调控因子的 mRNA 表达变化，以更好地了解 DOX 诱导肝毒性的潜在因素。结果表明，DOX 暴露会导致 MDA 水平升高和大鼠肝组织 GSH 含量显著减少。与氧化应激相关的代谢物一致，DOX 显著抑制了抗氧化系统成分的 mRNA 表达和酶活性。此外，DOX 暴露对研究的其他调节基因也有显著的不良影响。然而，我们发现 TA 可以减轻 DOX 引起的许多负面变化。本研究结果表明，TA 可能被认为是一种多功能的候选药物，可通过维持细胞生理、活力，特别是氧化还原平衡，预防 DOX 诱导的肝毒性。
