D4F prophylaxis enables redox and energy homeostasis while preventing inflammation during hypoxia exposure

Biomed Pharmacother. 2021 Jan:133:111083. doi: 10.1016/j.biopha.2020.111083. Epub 2020 Dec 8.

Abstract

Apo-A1 is correlated with conditions like hyperlipidemia, cardiovascular diseases, high altitude pulmonary edema and etc. where hypoxia constitutes an important facet.Hypoxia causes oxidative stress, vaso-destructive and inflammatory outcomes.Apo-A1 is reported to have vasoprotective, anti-oxidative, anti-apoptotic, and anti-inflammatory effects. However, effects of Apo-A1 augmentation during hypoxia exposure are unknown.In this study, we investigated the effects of exogenously supplementing Apo-A1-mimetic peptide on SD rats during hypoxia exposure. For easing the processes of delivery, absorption and bio-availability, Apo-A1 mimetic peptide D4F was used. The rats were given 10 mg/kg BW dose (i.p.) of D4F for 7 days and then exposed to hypoxia. D4F was observed to attenuate both oxidative stress and inflammation during hypoxic exposure. D4F improved energy homeostasis during hypoxic exposure. D4F did not affect HIF-1a levels during hypoxia but increased MnSOD levels while decreasing CRP and Apo-B levels. D4F showed promise as a prophylactic against hypoxia exposure.

Keywords: Apo-A1; D4F; Energy homeostasis; Hypoxia; Inflammation; Prophylaxis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Apolipoprotein A-I / pharmacology*
  • Apolipoproteins B / blood
  • Carrier Proteins / blood
  • Disease Models, Animal
  • Energy Metabolism / drug effects*
  • Hypoxia / blood
  • Hypoxia / complications
  • Hypoxia / drug therapy*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Inflammation / blood
  • Inflammation / etiology
  • Inflammation / prevention & control*
  • Lung / drug effects*
  • Lung / metabolism
  • Male
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Apolipoprotein A-I
  • Apolipoproteins B
  • Carrier Proteins
  • Crp protein, rat
  • D-4F peptide
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Superoxide Dismutase