Melatonin pretreatment modulates anti-inflammatory, antioxidant, YKL-40, and matrix metalloproteinases in endotoxemic rat lung tissue

Abstract

We aimed to investigate the effects of melatonin administered before and duringendotoxemia on the lung tissue of rats, cytokine, YKL-40, matrix metalloproteinase(MMP) and inhibitor levels, oxidative stress parameters, and energy balance.Sepsis was induced with lipopolysaccharide (LPS), the cell wall molecule of gramnegative bacteria. Rats were divided into four groups, Control, LPS (Escherichiacoli O127:B8, 20 mg/kg), melatonin (10 mg/kg), and melatonin+LPS (M+LPS).After injections, lung tissues samples were taken for experimental analyses. YKL-40, thiobarbituric acid reactive substances (TBARS), glutathione reductase (GR),glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) enzymes levelswere measured, high-energy components were analyzed; tumor necrosis factoralpha(TNF-α), MMP-2, YKL-40, MMP-9, myeloperoxidase (MPO), tissue inhibitorsof matrix metalloproteinase (TIMP)-1, and interleukin (IL)-10 immunoreactivitieswere investigated. In LPS group, YKL-40, creatine phosphate (both, p < 0.05), SOD,GR, adenosine mono-phophate (AMP), adenosine tri-phosphate (ATP) (for all,p < 0.01) were significantly decreased, while TBARS and adenosine di-phosphate(ADP) levels were increased (p < 0.01, p < 0.05; respectively) compared to othergroups. MMP-2 and -9, TIMP-1, TNF-α, IL-10, and MPO immunoreactivity wereinvestigated in LPS group. On the contrary, in M+LPS group, MMP-9, TIMP-1immunoreactivities were not found and IL-10 and MMP-2 immunoreactivities werefound with little involvement. In M+LPS group, YKL-40, GR, AMP, ATP, creatine phosphate (for all, p < 0.05), and SOD (p < 0.01)levels were significantly increased and TBARS levels were decreased (p < 0.05). In our study, we suggest that melatonin exerts aprotective and curative effect by reducing the matrix metalloproteinase levels responsible for tissue damage balance, stimulatingthe release of antioxidant enzymes, regulating cytokines and energy balance during endotoxemia.