Exposure to low levels of hexavalent chromium in drinking water alters diet-induced steatotic liver disease in male rats

Abstract

Ranked as a “top 10 cause of death”, chronic liver disease accounts for millions of deaths annually. The prevalence of the most prominent liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), has doubled over the past 20 years and continues to rise. Growing in parallel are environmental chemical exposures, emergingas key risk factors for liver disease. Hexavalent chromium [Cr(VI)] is the #1 chemical hazard in U.S. drinking water and is associated with increased liver disease incidence, including liver cancer. How Cr(VI) contributes to liver disease is poorly understood and no studies have considered whether Cr(VI) exposure together with high-fat diet, a well-established MASLD risk factor, drives liver disease. Thus, we developed an in vivo model to study the impact of Cr(VI) and high-fat diet on MASLD. Male Sprague Dawley rats were exposed to Cr(VI) in drinking water (0, 0.05, or 0.1 mg/L - levels that reflect the World Health Organization and U.S. Environmental Protection Agency maximum contaminant levels, respectively) and fed a normal or high-fat diet for 90 days. We observed high-fat diet significantly increased body mass, plasma lipoproteins and cholesterol, liver injury and hepatic triglycerides in rats and these outcomes were exacerbated by exposure to Cr(VI). Cr(VI) alone increased hepatic expression of alpha fetoprotein, a liver cancer biomarker, with evidence suggesting Cr(VI) and high-fat diet together increased these levels more than either exposure alone. Our results indicate Cr(VI) at very low levels combined with high-fat diet worsens liver disease, emphasizing the need to reconsider current Cr(VI) drinking water regulations.