T-2毒素通过激活铁和抑制血氧酶-1来诱导心脏毒性
1Chinese PLA Center for Disease Control and Prevention, Beijing, 100071, China; School of Public Health, China Medical University, Shenyang, 110122, China.
Chemosphere
|September 7, 2023
概括
T-2毒素通过激活细胞死亡通路ferroptosis来诱导心脏损伤. 向铁和血氧酶-1 (HO-1) 可能会防止T-2毒素心脏毒性.
科学领域:
- 毒理学 毒理学 毒理学
- 心血管生物学 心血管生物学
- 细胞死亡机制 细胞死亡机制
背景情况:
- 富沙衍生代谢物T-2毒素通过未知的机制引起心脏毒性.
- 铁,一种依赖于铁的细胞死亡,与心血管损伤有关.
研究的目的:
- 为了研究铁死在T-2毒素诱导的心脏毒性的作用.
- 探索氧酶-1 (HO-1) 在这个过程中的参与.
主要方法:
- 在使用T-2毒素的雄性小鼠和人类心肌细胞中引起的急性心脏毒性.
- 评估了氧化应激标志物,铁亡指标和HO-1表达.
- 使用了铁灭抑制剂 (利普罗克斯塔丁-1) 和HO-1抑制剂 (Sn-protoporphyrin).
主要成果:
- T-2毒素增加了活性氧物种,甲和铁 (Fe2+).
- T-2毒素降低了谷氨,ATP和谷氨过氧化酶4的水平,激活了铁亡.
- 使用Liproxstatin-1抑制铁亡可改善心脏损伤.
- T-2毒素降低了HO-1的调节,加剧了ferroptosis和氧化损伤.
结论:
- 铁亡是T-2毒素诱导心脏毒性的关键机制.
- 向铁和调节HO-1活动提供了潜在的心脏保护策略,防止T-2毒素暴露.
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