Role of parthenolide in paclitaxel-induced oxidative stress injury and impaired reproductive function in rat testicular tissue

by Selleckchem | Dec 28 2023

The chemotherapeutic agent paclitaxel (PTX) causes testicular toxicity due to oxidative stress. Parthenolide (PTL), the active ingredient of the Tanacetum parthenium plant, is used to treat inflammation, dizziness, and spasms. In the present study, we evaluated the therapeutic effect of PTL on PTX-induced testicular toxicity in rats and its role in reproductive function. To this end, 6 groups were formed: control, PTX, sham, T1, T2, and T3. After testicular toxicity was induced in rats with 8 mg/kg PTX, the rats were treated with 1 mg/kg, 2 mg/kg, and 4 mg/kg PTL for 14 days. GSH and MDA levels were measured in rat testicular tissue after the last dose of PTL was administered. To determine the damage caused by PTX to testicular tissue by detecting 8-OHdG and iNOS, sections were prepared and examined histopathologically and immunohistochemically. Furthermore, the gene expressions and enzymatic activities of SOD, CAT, GPx, GST, and GR were investigated in all groups. After PTL treatment, MDA, 8-OHdG, and iNOS levels decreased while GSH levels increased in testicular tissue. Increased levels of antioxidant genes and enzymes also reduced oxidative stress. Additionally, the expression levels of the Dazl, Ddx4, and Amh genes, which are involved in gametogenesis and sperm production, decreased in case of toxicity and increased with PTL treatment. The data from this study show that PTL may have a therapeutic effect in the treatment of testicular damage by eliminating the oxidative stress-induced damage caused by PTX in testicular tissue, providing an effective approach to alleviating testicular toxicity, and playing an important role in reproduction/sperm production, especially at a dose of 4 mg/kg.

Comments:

This study sounds quite comprehensive and insightful! The use of parthenolide (PTL) to counteract the testicular toxicity induced by paclitaxel (PTX) in rats seems promising. It's fascinating how the administration of different doses of PTL exhibited varying effects on oxidative stress markers and gene expressions related to reproductive function.

The reduction in MDA, 8-OHdG, and iNOS levels while increasing GSH levels after PTL treatment indicates its potential in mitigating oxidative stress induced by PTX. The fact that antioxidant gene expressions and enzymatic activities were positively impacted further supports PTL's role in reducing oxidative stress in the testicular tissue.

The study's exploration into gene expressions linked to gametogenesis and sperm production, such as Dazl, Ddx4, and Amh, provides valuable insights. The observed decrease in these gene expressions due to PTX-induced toxicity and their subsequent increase following PTL treatment highlights the potential therapeutic impact of PTL on reproductive function.

The findings suggest that PTL, especially at a dose of 4 mg/kg, could be an effective therapeutic approach for alleviating testicular damage caused by PTX and supporting reproductive health. However, further research, including long-term studies and potential human trials, would be necessary to solidify these findings and determine the safety and efficacy of PTL in clinical settings.