生物能量学中断,氧化应激和炎症是特拉马多尔诱导毒性的潜在机制
Ekramy M Elmorsy1, Huda A Al Doghaither2, Ayat B Al-Ghafari2,3
1Pathology Department, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
Journal of biochemical and molecular toxicology
|August 21, 2024
概括
特拉马多尔 (TR) 通过破坏细胞能量生产而导致损伤,导致细胞的氧化应激和炎症. 抗氧化剂和线粒体剂显示出对这种特拉马多尔毒性有保护的潜力.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- 特拉马多尔 (TR) 是一种用于中度至重度疼痛的广泛使用的止痛药.
- 使用TR与不良影响有关,包括损伤 (毒性).
- 了解TR诱导毒性的精确机制对于患者的安全至关重要.
研究的目的:
- 阐明特拉马多尔诱导的毒性背后的机制.
- 研究TR对脏近道管状细胞 (PTC) 的影响.
- 探索潜在的保护策略,防止TR诱导的损伤.
主要方法:
- 使用了3-(4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium化物和乳酸脱酶试验来评估PTC毒性.
- 进行生物能测试以评估线粒体功能和细胞呼吸.
- 测量了反应性氧物种 (ROS) 生产,氧化应激标志物和炎症性细胞因子表达.
主要成果:
- TR显著降低了PTC活力 (EC50值为9.8和11.5μM).
- TR破坏了线粒体功能,降低了ATP的产生,增加了乳酸释放.
- TR诱导了氧化应激,增加了ROS和脂质过氧化,并增加了炎症性细胞因子 (TNF-α,IL-6).
结论:
- 特拉马多尔通过损害细胞生物能学,促进氧化应激,并触发附近管状细胞的炎症来诱导毒性.
- 抗氧化剂,抗炎剂和线粒体激活剂表明对TR诱导的细胞毒性有保护作用.
- 针对生物能功能障碍,氧化应激和炎症可能为管理毒性提供治疗途径.
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