Endoglin inhibition by sodium acetate and flutamide ameliorates cardiac defective G6PD-dependent antioxidant defense in gestational testosterone-exposed rats - 20/09/18
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Graphical abstract |
The graphical abstract showing the effects of late gestational testosterone exposure on cardiac G6PD-dependent anti-oxidant system, adenosine deaminase/xanthine oxidase/uric acid pathway, and endoglin and the roles of flutamide, an androgen receptor blocker (ARB) and acetate, a short-chain fatty acid (SCFA).
Highlights |
• | Late gestational testosterone (Tes) exposure causes cardiac injury. |
• | Tes-induced cardiac injury is attributable to AR-mediated heightened endoglin and defective antioxidant defense. |
• | Ameliorative effect of acetate on Tes-induced cardiac injury is by suppressed endoglin, uric acid and enhanced antioxidant barrier. |
• | Acetate also has inhibitory effect on cardiac uric acid production. |
Abstract |
Gestational androgen excess has been implicated in the development of cardiac dysfunction with poor mechanistic 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.
Le texte complet de cet article est disponible en PDF.Keywords : Gestational androgen, Endoglin, G6PD-dependent antioxidant, Heart steatosis
Plan
Vol 107
P. 1641-1647 - novembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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