Adrenomedullin expression in aortic artery wall of diabetic rats given alpha lipoic acid

Pharmacol Rep. 2020 Aug;72(4):912-921. doi: 10.1007/s43440-020-00082-6. Epub 2020 Feb 27.

Abstract

Background: Diabetes mellitus (DM) is a major health problem predisposing to cardiovascular diseases. The aim of this study was to investigate the effects of alpha lipoic acid (ALA) on both the arterial wall of diabetic rats and the adrenomedullin (ADM) gene expression.

Methods: Twenty-four Wistar Albino rats were divided into three groups as Control, DM + S, and DM + ALA. For DM model, a single dose of 40 mg/kg streptozotocin, for DM + ALA group, 100 mg/kg/day/4 weeks was administered. Hematoxylin & Eosin (H&E) staining was done and vascular endothelial growth factor (VEGF) was detected by immunohistochemical analysis in the artery wall. Total damage score of vessel wall (endothelial cell damage, media layer smooth muscle cell damage, and internal elastic lamina damage) and H score (immunoreactivity intensity) were calculated. Expression of ADM gene was measured by qRT-PCR.

Results: In DM + S group, Total damage score of vessel wall were detected by light microscopy. There were statistically significant differences between the groups Control/DM + S and DM + S/DM + ALA in terms of the vessel total damage score and H score (p < 0.005). ADM expression was increased threefold in both DM + S and DM + ALA groups compared to the control group (p < 0.05).

Conclusions: ALA may have positive effect on the vessel damage in diabetic rats. However, no significant decrease in ADM expression levels was observed in diabetic rats after ALA administration and we considered that the protective effect of ALA is independent of adrenomedullin. Further studies with different doses and durations of ALA administrations are required to investigate the changes in ADM expression.

Keywords: Adrenomedullin; Alpha lipoic acid; Cardiovascular system; Diabetes mellitus; Vessel damage.

MeSH terms

  • Adrenomedullin / biosynthesis*
  • Adrenomedullin / genetics
  • Animals
  • Antioxidants / administration & dosage*
  • Aorta / drug effects
  • Aorta / metabolism*
  • Aorta / pathology
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Gene Expression
  • Male
  • Rats
  • Rats, Wistar
  • Thioctic Acid / administration & dosage*

Substances

  • Antioxidants
  • Adrenomedullin
  • Thioctic Acid