Endoglin inhibition by sodium acetate and flutamide ameliorates cardiac defective G6PD-dependent antioxidant defense in gestational testosterone exposed rats
No Thumbnail Available
Date
2018-08-25
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
Gestational androgen excess has been implicated in the development of cardiac dysfunction with poor me chanistic delineation. The role of sodium acetate on cardiac uric acid (UA) production and glucose-6-phosphate
dehydrogenase (G6PD)-dependent antioxidant defense in pregnancy is not known. The study therefore sought to
test the hypothesis that rats exposed to elevated testosterone in late pregnancy would have increased cardiac UA
production and defective G6PD-dependent antioxidant defense. We also hypothesized that sodium acetate (SAc)
or androgen receptor blocker, flutamide (Flu) would ameliorate these effects through endoglin inhibition.
Twenty-four pregnant Wistar rats were treated (sc) with olive oil, testosterone propionate (0.5 mg/kg) singly or
in combination with SAc (200 mg/kg; po) or Flu (7.5 mg/kg; po) in the late gestation between gestational day 14
and 19. The results showed that in the late gestation, testosterone exposure led to increased plasma and cardiac
endoglin. In the heart of rats exposed to gestational testosterone there were elevated lactate dehydrogenase,
adenosine deaminase, xanthine oxidase, uric acid (UA), cardiac injury markers and decreased G6PD-dependent
antioxidant defense. However, either SAc or Flu comparably ameliorated these testosterone-induced effects. The
data from the present study revealed that testosterone exposure in the late gestation causes elevated cardiac Eng
that is accompanied by increased UA production and defective G6PD-dependent anti-oxidant defenses. Besides,
the findings also suggest that the inhibitory effect of SAc or Flu on endoglin attenuates UA production and
enhances the G6PD-dependent anti-oxidant barrier, thereby implying that endoglin may be a potentially novel
therapeutic intervention for cardiac dysfunction particularly in pregnancy
Description
Keywords
Gestational androgen, Endoglin, G6PD-dependent antioxidant, Heart steatosis
Citation
Olatunji, L.A., Areola, E.D., & Badmus, O.O. (2018): Endoglin inhibition by sodium acetate and flutamide ameliorates cardiac defective G6PD-dependent antioxidant defense in gestational testosterone-exposed rats. Biomedicine and Pharmacotherapy, 107, 1641-1647, Published by Elsevier. Available online at: Biomedicine & Pharmacotherapy | Vol 107, Pages 1-1796 (November 2018) | ScienceDirect.com by Elsevier