Sivakumar Bhavana, Kurian Gino A
Vascular Biology lab, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, India.
School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, India.
Drug Chem Toxicol. 2023 Jan;46(1):15-23. doi: 10.1080/01480545.2021.2003698. Epub 2021 Nov 21.
The impact of PM2.5 from diesel exhaust (termed as diesel particulate matter (DPM)) on ischemia re-oxygenation (IR) injury and the consequent effect of fisetin to attenuate this injury remains unclear. IR was induced in H9c2 cells after 24 hrs of fisetin treatment. The cells when incubated with 100 µg/mL of DPM followed by IR, induced 60% cell death which was escalated to 78% with DPM exposure. Fisetin significantly attenuated IR induced cytotoxicity, improved mitochondrial activity and reduced oxidative stress in normal cells but failed to render protection against IR in presence of DPM. Isolated mitochondria experiment confirmed the mitotoxic effect of DPM. Immunoblot analysis established the failure of fisetin to activate PI3K/Akt signaling pathway. Based on the above observations, we concluded that fisetin mediated protection against IR was abrogated with DPM exposure due to augmented mitochondrial dysfunction and inactivation of PI3K/Akt signaling pathway.
柴油尾气中的细颗粒物（PM2.5，称为柴油颗粒物（DPM））对缺血再灌注（IR）损伤的影响以及杨梅素减轻这种损伤的后续作用仍不清楚。在对H9c2细胞进行24小时杨梅素处理后诱导产生IR。当细胞与100μg/mL的DPM一起孵育然后进行IR时，诱导了60%的细胞死亡，在暴露于DPM的情况下该比例升至78%。杨梅素显著减轻了IR诱导的细胞毒性，改善了线粒体活性并降低了正常细胞中的氧化应激，但在存在DPM的情况下未能对IR提供保护。分离线粒体实验证实了DPM的线粒体毒性作用。免疫印迹分析证实杨梅素未能激活PI3K/Akt信号通路。基于上述观察结果，我们得出结论，由于线粒体功能障碍加剧和PI3K/Akt信号通路失活，暴露于DPM会消除杨梅素介导的对IR的保护作用。
