Dexamethasone causes defective glucose-6-phosphate dehydrogenase dependent antioxidant barrier through endoglin in pregnant and nonpregnant rats

Can J Physiol Pharmacol. 2020 Oct;98(10):667-677. doi: 10.1139/cjpp-2018-0351. Epub 2020 Apr 7.

Abstract

Glucocorticoid therapy has been associated with adverse cardiometabolic effects during pregnancy. Inflammation-mediated cardiac dysfunction, an independent risk factor for morbidity and mortality, has been linked to defective glucose-6-phosphate dehydrogenase (G6PD) dependent antioxidant defenses and increased endoglin expression. We therefore sought to investigate the effects of dexamethasone (DEX) on cardiac endoglin and G6PD-dependent antioxidant defense. Twenty-four rats were randomly assigned to nonpregnant (PRE(-)), DEX-exposed nonpregnant (PRE(-) + DEX), pregnant (PRE(+)), and DEX-exposed pregnant (PRE(+) + DEX) rats, respectively (n = 6 per group). PRE(-) and PRE(+) rats received vehicle (per oral (po)), while PRE(-) + DEX and PRE(+) + DEX groups were administered DEX (0.2 mg/kg po) between gestational days 14 and 19, respectively. Results showed that DEX caused increased cardiac pro-inflammatory markers (adenosine deaminase (ADA) activity, endoglin, vascular cell adhesion molecule-1 (VCAM-1), tissue injury markers (LDH, GGT, AST, ALT, and ALP), metabolic disturbances (elevated fasting plasma glucose, free fatty acid (FFA), lactate, cardiac FFA, and lactate) and depressed G6PD-dependent antioxidant defenses (G6PD activity, reduced glutathione/oxidized glutathione ratio, and nitric oxide) in pregnant and nonpregnant rats. The present study demonstrates that DEX led to increased cardiac endoglin and VCAM-1 that is accompanied by defective G6PD-dependent antioxidant defenses but not cardiac lipid accumulation in both pregnant and nonpregnant rats.

Keywords: ADA; G6PD; VCAM-1; adénosine désaminase; dérivés réactifs de l’oxygène; endoglin; endogline; reactive oxygen species.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Cardiotoxicity
  • Dexamethasone / toxicity*
  • Endoglin / metabolism*
  • Energy Metabolism / drug effects
  • Female
  • Glucocorticoids / toxicity*
  • Glucosephosphate Dehydrogenase / metabolism*
  • Inflammation Mediators / metabolism
  • Lipid Peroxidation / drug effects
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / enzymology
  • Pregnancy
  • Rats, Wistar
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Antioxidants
  • Endoglin
  • Eng protein, rat
  • Glucocorticoids
  • Inflammation Mediators
  • Vascular Cell Adhesion Molecule-1
  • Dexamethasone
  • Glucosephosphate Dehydrogenase