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

Abstract

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. 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 (10mg/kg) (M-CLP) group. Serum and tissue samples were analysed. All procedures were carried out according to the ethical rules specified in Helsinki Declaration. 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). 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.