Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Int J Mol Sci. 2022 Mar 18;23(6):3315. doi: 10.3390/ijms23063315.
One of the major mechanisms of drug-induced liver injury includes mitochondrial perturbation and dysfunction. This is not a surprise, given that mitochondria are essential organelles in most cells, which are responsible for energy homeostasis and the regulation of cellular metabolism. Drug-induced mitochondrial dysfunction can be influenced by various factors and conditions, such as genetic predisposition, the presence of metabolic disorders and obesity, viral infections, as well as drugs. Despite the fact that many methods have been developed for studying mitochondrial function, there is still a need for advanced and integrative models and approaches more closely resembling liver physiology, which would take into account predisposing factors. This could reduce the costs of drug development by the early prediction of potential mitochondrial toxicity during pre-clinical tests and, especially, prevent serious complications observed in clinical settings.
药物性肝损伤的主要机制之一包括线粒体扰动和功能障碍。考虑到线粒体是大多数细胞中必不可少的细胞器,负责能量稳态和细胞代谢的调节,这并不奇怪。药物诱导的线粒体功能障碍可能受到多种因素和条件的影响,例如遗传易感性、代谢紊乱和肥胖、病毒感染以及药物。尽管已经开发出许多方法来研究线粒体功能,但仍需要更接近肝脏生理学的先进和综合模型和方法,并考虑到易感性因素。这可以通过在临床前试验中早期预测潜在的线粒体毒性来降低药物开发成本,特别是可以预防在临床环境中观察到的严重并发症。