Oxidative stress and inflammatory response of ghrelin on myocardial and aortic tissues in insulin-resistant rats

J Pharm Pharmacol. 2021 Mar 27;73(5):692-699. doi: 10.1093/jpp/rgab024.

Abstract

Objectives: This study was designed to clarify the effects of ghrelin on myocardial and aortic tissues in insulin-resistant rats.

Methods: Sprague-Dawley rats were divided into the following groups: control (Group 1), insulin resistance (IR, Group 2), ghrelin (Group 3) and IR+Ghrelin (Group 4) groups. Levels of HOMA-IR, fibronectin, hydroxyproline, collagen-1, collagen-3, matrix metalloproteinase-3, and matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1, and oxidative stress parameters as protein carbonyl (PCO), lipid hydroperoxides (LHPs), malondialdehyde, total thiol were determined in myocardial tissue. Expressions of IL-6, NF-κB and TNF-α mRNAs were detected by RT-qPCR. Aorta tissue was stained Masson trichrome.

Key findings: The HOMA-IR level decreased in the IR+Ghrelin group compared with the IR group (P < 0.001). The PCO and LHP concentrations were higher in the IR group compared with control rats (P < 0.05). The PCO level was reduced by ghrelin in the IR+Ghrelin group compared with the IR group (P < 0.001). Ghrelin treatment reduced the mRNA expression levels of IL-6, NF-κB and TNF-α in the IR+Ghrelin group compared with the IR group (P < 0.001). There was no difference among the groups in the histology of aortic tissue.

Conclusions: Ghrelin, a regulator of appetite and energy homeostasis, may be effective in regulating oxidative stress and the inflammatory response when impaired by IR. Therefore, ghrelin may reduce the risks of myocardial dysfunction in IR.

Keywords: ghrelin; heart; inflammation; insulin resistance; oxidative stress.

MeSH terms

  • Animals
  • Aorta / drug effects*
  • Aorta / physiopathology
  • Cytokines / metabolism
  • Extracellular Matrix Proteins / metabolism
  • Ghrelin / pharmacology*
  • Heart / drug effects*
  • Inflammation / drug therapy*
  • Insulin / blood
  • Insulin Resistance / physiology*
  • Myocardium
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cytokines
  • Extracellular Matrix Proteins
  • Ghrelin
  • Insulin