Abstract
Background: Binge drinking is a major systemic health concern. Binge drinking could alter renal metabolome and induce markers of injury as per our previously published work. Further investigation into the top regulated pathways revealed alterations sex hormone biosynthesis pathway was altered in a sex specific manner following 6 weeks of binge drinking. Our goal is to unveil individual metabolite mediators belonging to sex hormone biosynthesis pathway and to investigate the connecting link to cardiorenal health in both sexes following chronic binge drinking. Materials and Methods: For this work, n=3 male and female mice belonging to either control (water fed) or ethanol (20% fed in water) treatment groups were included. At the age of 8- 10 weeks, mice underwent water or binge (20% ethanol) drinking from Monday to Thursday for 4 hours, in dark cycle. This cycle was repeated for 6 weeks. Renal tissues from our experimental groups were collected at the end of 6 weeks and subjected to untargeted metabolomics. In brief, Ultra Performance Liquid Chromatography (UPLC) with Time-of-flight Mass Spectrometry (ESI-TOF-MS) followed by Mass spectrometry based separation was used to identify significantly altered metabolites. Results: Steroid hormone biosynthesis was the one among the top regulated pathways. Metabolites belonging to male hormone biosynthesis were the significantly altered one but specifically in females. Dehydroepiandrosterone, and it’s downstream 11-hydroxytestosterone were upregulated only in females and not in males. Female binge drinking group demonstrated an increase of 4.24 (fold) and 2.21 (fold) for dehydroepiandrosterone, and 11-hydroxytestosterone respectively as per the Log 2 Fold change values with a statistical significance of P<0.05 . Interestingly, this increase in male hormone metabolites we observed in females were also accompanied by an increase in metabolites of proinflammatory and prothrombotic mediators, thromboxane B3 and 5- Oxo- 12 HETE, of 2.3 (fold) and over 1.6 (fold) respectively as per Log 2 Fold change values and with a statistical difference of P<0.05 . Conclusion: Our data clearly demonstrate a sex specific effect following chronic binge drinking, where females have an increase in male hormones accompanied by an increase in prothrombotic and proinflammatory factors.
Published Version
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