School of Medicine, University of Belgrade, 11129 Belgrade, Serbia.
University Medical Centre "Bežanijska kosa", 11080 Belgrade, Serbia.
Int J Mol Sci. 2021 Mar 10;22(6):2798. doi: 10.3390/ijms22062798.
Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.
脂质在组织保护和损伤中都起着至关重要的作用。组织缺血会产生无氧条件，导致酶失活，再灌注会引发氧化应激，导致膜脂质的有害变化、醛的形成以及链损伤，直至细胞死亡。在细胞内的一系列有害事件中，关键事件是不必要的脂肪酸积累，从而导致脂毒性。脂质分析为缺血/再灌注 (I/R) 障碍的发病机制提供了更多的见解，并揭示了药物作用的新靶点。细胞中脂肪酸组成变化的特征，以及这些变化的时间进程，既表明了损伤的机制，也表明了新的治疗可能性。再灌注脂毒性的治疗方法包括减轻脂肪酸过载，即它们向脂肪组织的转运和/或抑制脂肪酸对细胞损伤和死亡的不良影响。后者涉及使用 PPAR 激动剂和药物来调节脂肪酸通过肉碱进入线粒体内部或长链脂肪酸向过氧化物酶体的转运。
