Investigation of the effect of melatonin administration on inflammatory mediators; MMP-2, TGF-β and VEGF levels in rats with sepsis

Int J Clin Pract. 2021 Nov;75(11):e14832. doi: 10.1111/ijcp.14832. Epub 2021 Sep 17.

Abstract

Aims: Sepsis causes life-threatening tissue and organ dysfunctions caused by endogenous mediators in response to infection. Melatonin is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. This study aimed to evaluate the changes in serum and liver tissue levels of VEGF, TGF-β and MMP-2 in melatonin-treated septic rats.

Materials and methods: Twenty-one Wistar-albino male rats were included in this study. Rats were randomly divided into three groups. Group 1 is sham-operated control (C) group, Group 2 is caecal ligation and puncture (CLP) group and Group 3 is melatonin-treated (10 mg/kg) (M-CLP) group. Serum and tissue samples were analysed. All procedures were carried out according to the ethical rules specified in Helsinki Declaration.

Results: Sera MMP-2 levels were found higher than tissue MMP-2 levels in C and CLP (respectively, P = .048, P = .01). In CLP and M-CLP, serum TGF-β levels were higher than tissue TGF-β levels(respectively, P = .05, P = .01). Serum VEGF levels in CLP were found to be significantly higher than both C and M-CLP(P < .01).

Conclusion: MMP-2 levels may have increased because of the prevention of oxidative damage in sepsis, and this may increase the anti-inflammatory effect. Melatonin treatment may have a therapeutic effect against sepsis since it prevents the increase in serum VEGF level. A powerful endogenous antioxidant, may be a promising therapeutic agent on the mortality and morbidity of the disease, because of its lowering effect on serum VEGF, which is a poor prognostic factor in sepsis.

Keywords: matrix metalloproteinases-2; melatonin; sepsis; transforming growth factor β; vascular endothelial growth factor.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Inflammation Mediators
  • Matrix Metalloproteinase 2
  • Melatonin* / pharmacology
  • Rats
  • Rats, Wistar
  • Sepsis* / drug therapy
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A

Substances

  • Inflammation Mediators
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 2
  • Melatonin