Subchronic Exposure to Hexavalent Chromium in Drinking-Water-Induced Sex-Dependent Essential Metal Dyshomeostasis in the Liver, Blood, and Brain of Guinea Pigs

Background/Objectives: Hexavalent chromium [Cr(VI)] is a toxic metal that enters the environment due to natural and anthropogenic processes. The liver is a major target organ of Cr(VI) exposure through drinking water, resulting in an increased risk of exposed individuals developing chronic liver diseases and cancers. Cr(VI) exposure is also associated with neurological dysfunction. Essential metal dyshomeostasis is a well-characterized biomarker of liver and neurological diseases, but the role Cr(VI) plays in altering essential metal levels in both organs is poorly understood. Methods: Male and female Hartley guinea pigs were exposed to 0 or 5 mg Cr(VI)/L in drinking water for 90 days. Chromium accumulation and essential metal levels in the liver, blood and brain were analyzed using inductively coupled plasma mass spectrometry. Results: Chromium significantly accumulated in a sex-dependent manner in the livers and blood of guinea pigs given 5 mg Cr(VI)/L in their drinking water, with sex- and region-specific chromium deposition observed in the brain. The livers and blood of female guinea pigs were more vulnerable to Cr(VI) exposure, as evident in the significant chromium accumulation and dyshomeostasis of several essential metals, including hepatic magnesium, zinc and potassium. Conversely, male guinea pigs were more vulnerable to Cr(VI)-induced essential metal dyshomeostasis in the brain, with significant changes in molybdenum and cobalt in nearly half of the 11 brain regions assessed. Conclusions: This study begins the process of establishing a novel model to study Cr(VI)-induced hepatotoxicity, neurotoxicity and organ crosstalk. Overall, Cr(VI) induced sex-dependent essential metal dyshomeostasis in the liver and blood, along with sex- and region-specific essential metal dyshomeostasis in the brain. These results suggest essential metal dyshomeostasis may play an important role in Cr(VI)-induced liver and neurodegenerative diseases, and these effects should guide future mechanistic investigations.