Sodium acetate and androgen receptor blockade improve gestational androgen excess-induced deteriorated glucose homeostasis and antioxidant defenses in rats: Roles of adenosine deaminase and xanthine oxidase activities

dc.contributor.authorUsman, Taofeek Oluwamayowa
dc.contributor.authorAreola, Emmanuel Damilare
dc.contributor.authorBadmus, Olufunto
dc.contributor.authorKim, InKyeom
dc.contributor.authorOlatunji, Lawrence Aderemi
dc.date.accessioned2025-05-07T11:37:43Z
dc.date.available2025-05-07T11:37:43Z
dc.date.issued2018-08-29
dc.description.abstractNutritional challenges and androgen excess have been implicated in the development of gestational diabetes and poor fetal outcome, but the mechanisms are not well delineated. The effects of short chain fatty acid (SCFA) on glucose dysmetabolism and poor fetal outcome induced by gestational androgen excess is also not known. We tested the hypothesis that blockade of androgen receptor (AR) and suppression of late gestational androgen excess prevents glucose dysmetabolism and poor fetal outcome through suppression of adenosine deaminase (ADA)/xanthine oxidase (XO) pathway. Twenty-four pregnant Wistar rats were treated (sc) with olive oil, testosterone propionate (0.5 mg/kg) singly or in combination with SCFA (sodium acetate; 200 mg/kg; po) or AR blocker (flutamide; 7.5 mg/kg; po) between gestational days 14 and 19. The results showed that late gestational androgen excess led to glucose deregulation, poor fetal outcome, increased plasma and hepatic free fatty acid and lactate dehydrogenase, liver function marker enzymes, malondialdehyde, uric acid, ADA and XO activities. Conversely, gestational androgen excess resulted in reduced body weight gain, visceral adiposity, plasma and hepatic anti-oxidant defenses (glutathione peroxidase, reduced glutathione/glutathione disulphide ratio, glucose-6-phosphate dehydrogenase, adenosine and nitric oxide). However, all these effects were ameliorated by either sodium acetate or flutamide treatment. The study demonstrates that suppression of testosterone by SCFA or AR blockade protects against glucose deregulation and poor fetal outcome by improvement of anti-oxidant defenses and replenishment of hepatic oxidative capacity through suppression of ADA/XO pathway. Hence, utility of SCFA should be encouraged for prevention of glucose dysmetabolism and poor fetal outcome.
dc.description.sponsorshipThis study was supported by the International Society of Hypertension (ISH) through the ISH grant for mentors (2017) and Association of African Universities grant (AAU/2017/2018)
dc.identifier.citationUsman, T.O., Areola, E.D., Badmus, O.O., Kim, I., & Olatunji, L.A. (2018). Sodium acetate and androgen receptor blockade improve gestational androgen excess-induced deteriorated glucose homeostasis and antioxidant defenses in rats: roles of adenosine deaminase and xanthine oxidase activities. Journal of Nutritional Biochemistry, 62, 65-75, Published by Elsevier. Available online at: JNB | The Journal of Nutritional Biochemistry | Vol 62, Pages 1-256 (December 2018) | ScienceDirect.com by Elsevier
dc.identifier.other10.1016/j.jnutbio.2018.08.018
dc.identifier.urihttps://uilspace.unilorin.edu.ng/handle/123456789/16341
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofseries62; 65-75
dc.subjectAndrogen receptor
dc.subjectgestational testosterone
dc.subjectgut microbiota metabolites
dc.subjecthepatic anti-oxidant
dc.subjectSCFA
dc.titleSodium acetate and androgen receptor blockade improve gestational androgen excess-induced deteriorated glucose homeostasis and antioxidant defenses in rats: Roles of adenosine deaminase and xanthine oxidase activities
dc.title.alternativeAcetate and AR blockade improves glucoregulation and antioxidant barriers
dc.typeArticle

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