Scholarlink

Background <p>Cisplatin (Cisp) is a common chemotherapeutic drug that has demonstrated effectiveness against number of cancers. However, its dose-limiting toxicities, such as hepatotoxicity, limit its therapeutic usefulness. Methylene blue (MB), a substance derived from phenothiazine, has significant antioxidant qualities. This study investigated the protective effects of Methylene blue (MB) against Cisplatin-induced hepatotoxicity and the involvement of the anti-inflammatory, the anti-oxidant and the iron regulating effects in male Wistar.</p> Methods <p>Albino rats. Rats were divided into four groups: control, Cisplatin (Cisp, 8&#xa0;mg/kg, IP), and two MB-treated groups (25&#xa0;mg/kg and 50&#xa0;mg/kg, IP) with Cisp.</p> Results <p>Cisp administration (8&#xa0;mg/kg, IP) significantly impaired liver function, increased oxidative stress, promoted apoptosis (increased BAX, CASPASE-3, and decreased BCL2) and disrupted homeostasis by increasing the ferroptosis upstream ferritinophagy (decreased ferritin and increased NCOA4). Treatment with MB at doses of 25&#xa0;mg/kg and 50&#xa0;mg/kg demonstrated dose-dependent hepatoprotective effects. The higher dose (50&#xa0;mg/kg) of MB effectively restored liver function markers, antioxidant status, hindered apoptosis and regulated iron regulatory proteins (ferritin and NCOA4 that reflects ferritinophagy) to levels comparable with the control group. MB treatment significantly reduced lipid peroxidation inhibited apoptotic pathways, and modulated iron-related gene expression. The 50&#xa0;mg/kg dose consistently outperformed the 25&#xa0;mg/kg dose across all measured parameters.</p> Conclusion <p>These findings suggest that MB, particularly at higher doses, may serve as a promising therapeutic agent in mitigating Cisp-induced hepatotoxicity by reducing oxidative stress, regulating iron homeostasis/ferritinophagy/ferroptosis, and inhibiting apoptotic pathways.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Methylene blue confers protection against hepatotoxicity induced by Cisplatin; the involvement of oxidative stress, apoptosis and NCOA4-mediated ferritinophagy

  • 期刊论文

  • 发表日期：

    2026年4月22日

查看全文
  • Marawan A. Elbaset,
  • Bassim M. S. A. Mohamed,
  • Passant E. Moustafa,
  • Yosra Assem Hussien,
  • Zeinab A. El-Gendy,
  • Alyaa Farouk Hessin,
  • Mohamed A. Mohamady Hussein,
  • Reda MS Korany,
  • Hany G. Attia,
  • Ashraf Azar,
  • Hany M. Fayed,
  • Bassim

摘要

Background

Cisplatin (Cisp) is a common chemotherapeutic drug that has demonstrated effectiveness against number of cancers. However, its dose-limiting toxicities, such as hepatotoxicity, limit its therapeutic usefulness. Methylene blue (MB), a substance derived from phenothiazine, has significant antioxidant qualities. This study investigated the protective effects of Methylene blue (MB) against Cisplatin-induced hepatotoxicity and the involvement of the anti-inflammatory, the anti-oxidant and the iron regulating effects in male Wistar.

Methods

Albino rats. Rats were divided into four groups: control, Cisplatin (Cisp, 8 mg/kg, IP), and two MB-treated groups (25 mg/kg and 50 mg/kg, IP) with Cisp.

Results

Cisp administration (8 mg/kg, IP) significantly impaired liver function, increased oxidative stress, promoted apoptosis (increased BAX, CASPASE-3, and decreased BCL2) and disrupted homeostasis by increasing the ferroptosis upstream ferritinophagy (decreased ferritin and increased NCOA4). Treatment with MB at doses of 25 mg/kg and 50 mg/kg demonstrated dose-dependent hepatoprotective effects. The higher dose (50 mg/kg) of MB effectively restored liver function markers, antioxidant status, hindered apoptosis and regulated iron regulatory proteins (ferritin and NCOA4 that reflects ferritinophagy) to levels comparable with the control group. MB treatment significantly reduced lipid peroxidation inhibited apoptotic pathways, and modulated iron-related gene expression. The 50 mg/kg dose consistently outperformed the 25 mg/kg dose across all measured parameters.

Conclusion

These findings suggest that MB, particularly at higher doses, may serve as a promising therapeutic agent in mitigating Cisp-induced hepatotoxicity by reducing oxidative stress, regulating iron homeostasis/ferritinophagy/ferroptosis, and inhibiting apoptotic pathways.