Sex Differences in Antioxidant Gene Expression in response to Chronic Arsenic Exposure

Abstract

Inorganic arsenic is highly toxic metalloid considered a water contaminant that is naturally occurring through geological formations where it leaches into ground water sources and is anthropogenically sourced through pollution and found in surface water as a contaminant. Acute and chronic arsenic exposure can stimulate the production of reactive oxygen species and increase systemic oxidative stress. The aim of the present study was to investigate sex differences in the redox response induced by chronic arsenic exposure in a murine model.Twenty‐four (12 female & 12 male) 10‐wk old mice were randomized to arsenic treatment or control. Arsenic groups were exposed to controlled arsenic levels (10µM = ppb = ug/L) via drinking water for 8‐wks. Following the treatment, mice were euthanized, and skeletal muscle was collected. The tissue was homogenized and processed for measures of gene expression for seven antioxidant genes (Sod2, Cas1, Gpx, Gst, Gsr, Gclc, Nrf2). One‐way ANOVA was performed with post‐hoc comparisons depending on normality of data. Interactions between sex and arsenic were determined using univariate testing.There was a significant sex‐by‐treatment interaction for Cas1, Gpx1, Gsr, Gclc, and Nrf2 where the female mice treated with arsenic responded by upregulating these genes in comparison to controls (p<0.05), whereas the males did not. Only Sod2 was lower in the arsenic treated female mice versus controls and there were no effects on Gst across the 4 groups.These data demonstrate that sex differences only emerged under stimulated conditions (arsenic exposure) and support the protective role of estrogen in antioxidant defenses.