US Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment, Cincinnati, OH 45268, USA.
Int J Toxicol. 2012 Nov-Dec;31(6):551-63. doi: 10.1177/1091581812466418. Epub 2012 Nov 29.
Liver disease is a major health issue characterized by several pathological changes, with steatosis (fatty liver) representing a common initial step in its pathogenesis. Steatosis is of critical importance because prevention of fatty liver can obviate downstream pathologies of liver disease (eg, fibrosis). Recent studies have shown a strong correlation between chemical exposure and steatosis. The work described here identifies chemicals on the US Environmental Protection Agency's Integrated Risk Information System (IRIS) that induce steatosis and investigates putative mechanisms by which these chemicals may contribute to this pathological condition. Mitochondrial impairment, insulin resistance, impaired hepatic lipid secretion, and enhanced cytokine production were identified as potential mechanisms that could contribute to steatosis. Taken together, this work is significant because it identifies multiple mechanisms by which environmental chemicals may cause fatty liver and expands our knowledge of the possible role of environmental chemical exposure in the induction and progression of liver disease.
肝脏疾病是一个主要的健康问题，其特征是多种病理变化，其中脂肪变性（脂肪肝）是其发病机制中的一个常见初始步骤。脂肪变性非常重要，因为预防脂肪肝可以避免肝脏疾病的下游病理变化（例如纤维化）。最近的研究表明，化学物质暴露与脂肪变性之间存在很强的相关性。这里描述的工作确定了美国环境保护署综合风险信息系统（IRIS）上可诱导脂肪变性的化学物质，并研究了这些化学物质可能导致这种病理状况的假定机制。线粒体损伤、胰岛素抵抗、肝脂质分泌受损和细胞因子产生增加被确定为可能导致脂肪变性的潜在机制。总之，这项工作意义重大，因为它确定了环境化学物质可能导致脂肪肝的多种机制，并扩展了我们对环境化学物质暴露在诱导和进展肝脏疾病中的可能作用的认识。
