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
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Date
2018-08-29
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Elsevier
Abstract
Nutritional 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.
Description
Keywords
Androgen receptor, gestational testosterone, gut microbiota metabolites, hepatic anti-oxidant, SCFA
Citation
Usman, 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