Toraman Emine, Ceylan Hamid
Science Faculty, Department of Molecular Biology and Genetics, Atatürk University, 25240, Erzurum, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May 10. doi: 10.1007/s00210-025-04238-0.
Reproductive and testicular toxicity is one of the most important side effects of doxorubicin (DOX), a chemotherapy drug. In our study, we investigated the ameliorative effect of tannic acid (TA), a polyphenol, against DOX-induced testicular and reproductive toxicity in rats. For this purpose, rats divided into four groups (n = 5 each). Rats were treated with DOX cumulatively 30 mg/kg (5 mg/kg by six equal injections) for 2 weeks to induce testicular toxicity. Rats were then treated daily with TA (50 mg/kg) and DOX + TA combination. After treatments, animals were decapitated and testicular tissues were removed. Then, to examine the effect of DOX and TA treatments on oxidative stress, changes in Sod, Cat, Gpx, Gst, and Gr specific activities and mRNA levels were determined. To determine the effects on inflammation, changes in the expression levels of Tnf-α, IL6, Foxo1, Foxo3, Cox2, and Inos genes were examined. In order to examine the therapeutic effect of TA on the spermatogenesis process, mRNA levels of Dazl, Amh, and Ddx4, which regulate reproductive functions, were determined. Additionally, changes in oxidative damage markers GSH, MDA, 8-OHdG, iNOS, and TNF-a and changes in mitochondrial DNA copy number were also investigated. The results showed that DOX treatment caused a decrease in the levels of oxidative stress and reproductive parameters and an increase in inflammation and DNA damage parameters. However, it was determined that oxidative stress, inflammation, and tissue damage decreased in testicular tissue after TA treatment. In addition, it was observed that TA also improved the expression levels of reproductive genes. When all the data were evaluated together, it was determined that TA administration has a therapeutic effect against the damage and toxicity caused by DOX.
生殖和睾丸毒性是化疗药物阿霉素（DOX）最重要的副作用之一。在我们的研究中，我们研究了多酚鞣酸（TA）对DOX诱导的大鼠睾丸和生殖毒性的改善作用。为此，将大鼠分为四组（每组n = 5）。大鼠连续2周累积给予30 mg/kg DOX（分六次等量注射，每次5 mg/kg）以诱导睾丸毒性。然后，大鼠每天接受TA（50 mg/kg）和DOX + TA联合治疗。治疗后，将动物断头并取出睾丸组织。然后，为了检查DOX和TA治疗对氧化应激的影响，测定了Sod、Cat、Gpx、Gst和Gr的比活性及mRNA水平的变化。为了确定对炎症的影响，检测了Tnf-α、IL6、Foxo1、Foxo3、Cox2和Inos基因表达水平的变化。为了检查TA对精子发生过程的治疗效果，测定了调节生殖功能的Dazl、Amh和Ddx4的mRNA水平。此外，还研究了氧化损伤标志物GSH、MDA、8-OHdG、iNOS和TNF-a的变化以及线粒体DNA拷贝数的变化。结果表明，DOX治疗导致氧化应激水平和生殖参数降低，炎症和DNA损伤参数增加。然而，确定TA治疗后睾丸组织中的氧化应激、炎症和组织损伤减少。此外，观察到TA还改善了生殖基因的表达水平。综合评估所有数据后，确定给予TA对DOX引起的损伤和毒性具有治疗作用。
