Division of Experimental Medicine, McGill University, Montréal, Québec, Canada.
Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
Curr Environ Health Rep. 2024 Dec;11(4):547-556. doi: 10.1007/s40572-024-00463-6. Epub 2024 Nov 5.
Worldwide, there is an increasing prevalence of hepatic diseases. The most common diseases include alcoholic-associated liver disease (ALD), metabolic dysfunction-associated fatty liver disease/ metabolic dysfunction-associated steatohepatitis (MAFLD/MASH) and viral hepatitis. While there are many important mediators of these diseases, there is increasing recognition of the importance of the inflammatory immune response in hepatic disease pathogenesis.
Hepatic inflammation triggers the onset and progression of liver diseases. Chronic and sustained inflammation can lead to fibrosis, then cirrhosis and eventually end-stage cancer, hepatocellular carcinoma. Importantly, growing evidence suggest that metal exposure plays a role in hepatic disease pathogenesis. While in recent years, studies have linked metal exposure and hepatic steatosis, studies emphasizing metal-induced hepatic inflammation are limited. Hepatic inflammation is an important hallmark of fatty liver disease. This review aims to summarize the mechanisms of arsenic (As), cadmium (Cd) and chromium (Cr)-induced hepatic inflammation as they contribute to hepatic toxicity and to identify data gaps for future investigation.
在全球范围内,肝脏疾病的发病率呈上升趋势。最常见的疾病包括酒精性肝病(ALD)、代谢功能障碍相关脂肪性肝病/代谢相关性脂肪性肝炎(MAFLD/MASH)和病毒性肝炎。虽然这些疾病有许多重要的介质,但人们越来越认识到炎症免疫反应在肝脏疾病发病机制中的重要性。
肝脏炎症引发肝脏疾病的发生和进展。慢性和持续的炎症可导致纤维化,继而导致肝硬化,最终导致终末期癌症,即肝细胞癌。重要的是,越来越多的证据表明,金属暴露在肝脏疾病发病机制中起作用。近年来,研究已经将金属暴露与肝脂肪变性联系起来,但强调金属诱导的肝脏炎症的研究有限。肝脏炎症是脂肪性肝病的一个重要标志。本综述旨在总结砷(As)、镉(Cd)和铬(Cr)诱导肝脏炎症的机制,因为它们导致肝脏毒性,并确定未来研究的空白点。