Early-life Exposure to Inorganic Arsenic

Early-life exposure to inorganic arsenic exacerbates the development of fatty liver disease

In October, Kathryn Bambino, PhD was awarded $25,000 to investigate how early-life exposure to inorganic arsenic (iAs) leads to increased risk of mortality, liver, and metabolic disease. The association between iAs and adverse health outcomes puts iAs at the #1 position on the American Toxic Substances and Disease Registry (ATSDR) watch list. While the idea that environmental exposures modify the severity of common diseases, such as diabetes and obesity, few studies have addressed this possibility directly.

Co-investigators on the research include: Manish Arora, BDS, MPH, PhDChristine Austin, PhD of the CEHC, Jaime Chu, MD, Assistant Professor of Pediatrics at Mount Sinai, and Christoph Buettner, MD, PhD Professor of Medicine and Associate Professor of Neuroscience at Mount Sinai.

Since October, they have been using zebrafish to identify the mechanistic basis of iAs toxicity in metabolic disease. Fatty liver is the hepatic manifestation of metabolic syndrome and is also caused by alcohol abuse. However, not all people who drink excessively develop fatty liver disease (FLD). A widely proposed but untested hypothesis is that additional environmental exposures synergize with ethanol to cause FLD.

Their preliminary data has shown that iAs exposure is sufficient to cause FLD accompanied by activation of the unfolded protein response (UPR), a pathway that has been shown to be a common, causative mechanism of alcoholic and non-alcoholic fatty liver. They have found that exposure to iAs during early development synergistically interacts with ethanol to cause steatosis, activate the UPR, and cause severe toxicity and lethality.

Through the end of September 2017, Kathryn and her co-investigators hope to find a correlation between iAs and ethanol exposure with the diverse outcomes of alcohol abuse. Further studies will seek to elucidate the mechanism by which early-life exposure to iAs leads to progressive liver disease.