Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Jeonnam, Republic of Korea.
Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Jeonnam, Republic of Korea.
Environ Pollut. 2022 Sep 15;309:119780. doi: 10.1016/j.envpol.2022.119780. Epub 2022 Jul 13.
There is a scarcity of studies on the interactions between heavy metals and non-alcoholic fatty liver disease (NAFLD). Using a variety of statistical approaches, we investigated the impact of three common heavy metals on liver enzymes and NAFLD markers in a Korean adult population. We observed that cadmium, mercury, and lead all demonstrated positive correlations with liver enzymes and NAFLD indices. Our findings were mostly robust in secondary analysis, which included three novel mixture modeling approaches (WQS, qgcomp, and BKMR) as well as in silico investigation of molecular mechanisms (genes, miRNAs, biological processes, pathways, and illnesses). The 16 genes interacted with a mixture of heavy metals, which was linked to the development of NAFLD. Co-expression was discovered in nearly half of the interactions between the 18 NAFLD-linked genes. Key molecular pathways implicated in the pathogenesis of NAFLD generated by the heavy metal combination include activated oxidative stress, altered lipid metabolism, and increased cytokines and inflammatory response. Heavy metal exposure levels were related to liver enzymes and NAFLD indices, and cutoff criteria were revealed. More studies are needed to validate our findings and gain knowledge about the effects of chronic combined heavy metal exposure on adult and child liver function and the likelihood of developing NAFLD. To reduce the occurrence of NAFLD, early preventative and regulatory actions (half-yearly screening of workers at high-risk facilities; water filtration; avoiding excessive amounts of seafood, etc.) should be taken.
关于重金属与非酒精性脂肪性肝病(NAFLD)之间的相互作用的研究很少。我们采用多种统计方法,研究了韩国成年人群中三种常见重金属对肝酶和 NAFLD 标志物的影响。我们观察到,镉、汞和铅均与肝酶和 NAFLD 指数呈正相关。我们的发现主要在二次分析中具有稳健性,其中包括三种新的混合建模方法(WQS、qgcomp 和 BKMR)以及分子机制的计算研究(基因、miRNA、生物过程、途径和疾病)。与 NAFLD 发生相关的是,16 个基因与重金属混合物相互作用。在 18 个与 NAFLD 相关的基因中,几乎有一半的相互作用存在共表达。由重金属组合引起的 NAFLD 发病机制中的关键分子途径包括氧化应激激活、脂质代谢改变以及细胞因子和炎症反应增加。重金属暴露水平与肝酶和 NAFLD 指数相关,并揭示了截断标准。需要更多的研究来验证我们的发现,并了解慢性联合重金属暴露对成人和儿童肝功能以及发生 NAFLD 的可能性的影响。为了减少 NAFLD 的发生,应采取早期预防和监管措施(对高风险设施的工人进行半年一次的筛查;水过滤;避免过量食用海鲜等)。