吡罗列嗪生物碱(PAs)是一种分布在各种植物中的植物毒素,包括许多草药。许多器官可能因摄入PA而受伤,肝脏是最容易受到影响的.诊断,毒理学机制,和解毒PA诱导的肝毒性已经研究了几十年,这对它的预防具有重要意义,诊断,和治疗。当肝脏暴露于PA时,肝窦内皮细胞(LSEC)丢失,出血,肝实质细胞死亡,结节再生,枯否细胞激活,和纤维化发生。这些病理变化将PAs引起的肝损伤归类为急性,亚急性,和慢性类型。PAs代谢激活,线粒体损伤,谷胱甘肽(GSH)消耗,炎症,LSECs损伤诱导的凝血系统激活在PAs诱导的肝毒性的病理过程中起关键作用。很多天然化合物,如甘草酸,(-)-表儿茶素,槲皮素,黄芩素,绿原酸,等被证明是有效减轻PAs引起的肝损伤,这使得它们有巨大的潜力被开发为临床PA中毒的治疗药物。这篇综述提供了有关诊断的最新信息,毒理学机制,以及对PAs诱导的肝毒性的解毒研究。
Pyrrolizidine alkaloids (PAs) are one type of phytotoxins distributed in various plants, including many medicinal herbs. Many organs might suffer injuries from the intake of PAs, and the liver is the most susceptible one. The diagnosis, toxicological mechanism, and detoxification of PAs-induced hepatotoxicity have been studied for several decades, which is of great significance for its prevention, diagnosis, and therapy. When the liver was exposed to PAs, liver sinusoidal endothelial cells (LSECs) loss, hemorrhage, liver parenchymal cells death, nodular regeneration, Kupffer cells activation, and fibrogenesis occurred. These pathological changes classified the PAs-induced liver injury as acute, sub-acute, and chronic type. PAs metabolic activation, mitochondria injury, glutathione (GSH) depletion, inflammation, and LSECs damage-induced activation of the coagulation system were well recognized to play critical roles in the pathological process of PAs-induced hepatotoxicity. A lot of natural compounds like glycyrrhizic acid, (-)-epicatechin, quercetin, baicalein, chlorogenic acid, and so on were demonstrated to be effective in alleviating PAs-induced liver injury, which rendered them huge potential to be developed into therapeutic drugs for PAs poisoning in clinics. This review presents updated information about the diagnosis, toxicological mechanism, and detoxification studies on PAs-induced hepatotoxicity.