Untargeted metabolomics reveal sex-specific and non-specific redox-modulating metabolites in kidneys following binge drinking

Abstract

Binge drinking is a growing health concern among all age groups. The ability of individuals to handle ethanol in their systems differs not due to differences in enzyme expression but also due to other factors. Vital organs including brain, liver, heart, and kidneys are at high risk following repeated exposure to high concentrations of ethanol from binge drinking. The impact of chronic binge drinking on kidneys is not well studied. Using a mouse model of chronic binge drinking, we have identified major metabolic alterations that could set the stage for detrimental effects in the kidneys of male and female mice. We have deciphered that even though there are pathway overlaps, the different sexes exhibited unique and divergent metabolic pathway dysregulations as per the metabolite panels following binge drinking. We have reported that binge drinking could negatively influence renal redox homeostasis in both sexes through the regulation of different metabolite clusters. In male mice by downregulation of pantothenic acid and riboflavin synthesis, and in female mice by upregulation of α-aminoadipic acid and formyl kynurenine level. Interestingly, the uric acid biosynthesis pathway has been upregulated independent of the sex-specific effects, portraying the significance of uric acid as a potential marker for binge drinking-induced injury in both sexes. Thus, by altering renal metabolome, binge drinking sets the stage for renal damage by disturbing renal redox balance. Our data has high translational potential and will aid in finding ideal t herapeutics in a sex-specific manner for subjects exposed to binge drinking- induced renal injury.

Keywords

• chronic binge drinking
• ethanol metabolism
• metabolites
• untargeted metabolomics
• renal complications