In Utero Exposure to Mercury Is Associated With Increased Susceptibility to Liver Injury and Inflammation in Childhood

Abstract

Background and Aims Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant‐associated fatty liver disease. Approach and Results We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother–child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5‐8.7) from the European Human Early‐Life Exposome cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 μg/L; IQR, 1.1‐3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation‐related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating IL‐1β, IL‐6, IL‐8, and TNF‐α. Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up‐regulation of genes encoding these four cytokines and increased concentrations of IL‐8 and TNF‐α in the supernatants. Conclusions These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.

Association of Prenatal Exposure to Endocrine-Disrupting Chemicals With Liver Injury in Children

“…Prenatal exposures to PFASs and mercury were previously associated with elevated ALT levels and liver injury in children in the HELIX project. 17,18 Previous cross-sectional studies 16,50 reported positive associations between the plasma or serum concentration of PFASs, including perfluorooctanoic acid, perfluoro-octane sulfonate, perfluorononanoic acid, and perfluorohexane sulfonate, and liver enzyme levels and/or nonalcoholic steatohepatitis in US children. Similarly, among metals, mercury exposure had been linked to elevated ALT levels in adolescents in the US NHANES 51 and increased ALT and GGT levels in adults from South Korea.…”

Systemic maternal inflammation promotes ASD via IL-6 and IFN-γ

“…This conflicting data may be in part due to the potential biphasic effects of such toxins in either activating or blunting the immune system, especially in the case of cadmium [ 110 ], or may indicate that other factors such as maternal metabolism or immune responsivity may influence the effects of these xenobiotics. Importantly, exposure to heavy metals such as arsenic, lead, cadmium and mercury have all been associated with increased immune activation, and specifically enhanced IL-6 and IFNγ production, in several preclinical and clinical contexts [ 111–116 ]; however, systematic in vivo studies evaluating these compounds’ effects on cytokine levels in the developing brain is still required. While there is a strong association between immune-activating external stressors (e.g., viral infections, pollution and other toxins) and neurodevelopmental abnormalities that may manifest as ASD, further preclinical and clinical research is needed to fully understand the mechanisms by which these extrinsic factors directly influence fetal neurogenesis and neurodevelopmental abnormalities.…”

GOS Ameliorates Nonalcoholic Fatty Liver Disease Induced by High Fat and High Sugar Diet through Lipid Metabolism and Intestinal Microbes

“…Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in most regions of the world. It is a cause of the high incidence of end-stage liver disease worldwide and an inducer of hepatocellular carcinoma (HCC) [1,2]. A study showed that the total prevalence of NAFLD in China from 1999 to 2018 was 29.6% (95% CI: 28.2-31.0%), and the total number of patients with NAFLD in China is expected to increase to 314.58 million by 2030 [3].…”