We aimed to investigate the effects of melatonin administered before and during endotoxemia 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 gram negative bacteria. Rats were divided into four groups, Control, LPS (Escherichia coli 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 levels were measured, high-energy components were analyzed; tumor necrosis factor-alpha (TNF-α), MMP-2, YKL-40, MMP-9, myeloperoxidase (MPO), tissue inhibitors of matrix metalloproteinase (TIMP)-1, and interleukin (IL)-10 immunoreactivities were 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 other groups. MMP-2 and -9, TIMP-1, TNF-α, IL-10, and MPO immunoreactivity were investigated in LPS group. On the contrary, in M+LPS group, MMP-9, TIMP-1 immunoreactivities were not found and IL-10 and MMP-2 immunoreactivities were found 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 a protective and curative effect by reducing the matrix metalloproteinase levels responsible for tissue damage balance, stimulating the release of antioxidant enzymes, regulating cytokines and energy balance during endotoxemia.

Melatonin is a powerful endogenous antioxidant hormone. Its healing effects on energy balance and neuronal damage associated with oxidative metabolism disorders have been reported in pathologic conditions. We aimed to determinate the utility of melatonin on neuronal damage, synaptic transmission, and energy balance in the brain tissue of rats with sepsis induced with LPS. Rats was divided into four groups such as control, LPS (20 mg/kg i.p.), melatonin (10 mg/kg i.p. × 3), and LPS + Melatonin (LPS + Mel). After 6 h from the first injection, rats were decapitated, and also tissue and serum samples were taken. Lipid peroxidation and neuron-specific enolase (NSE) levels were determined from the serum in all group. High energy compounds, creatine, and creatine phosphate are measured by HPLC methods from the homogenized tissue. Counts of living neurons are marked with NeuN (neuronal nuclei), degenerated neurons are marked with S100-ß and synaptic vesicles transmission is analyzed with synaptophysin antibodies immunoreactivities. One-way ANOVA and post hoc Tukey tests were used to statistical analysis. In LPS group, AMP, ATP, creatine, and creatine phosphate levels were significantly decreased ( p < 0.05), and also ADP levels were significantly increased compared with the other groups ( p < 0.01). Living neurons counts were significantly decreased in LPS ( p < 0.01), melatonin, and LPS + Melatonin ( p < 0.05) groups compared with control. Degenerated neurons counts were increased in LPS group compared with control ( p < 0.01) and also decreased in both of melatonin and LPS + Melatonin groups ( p < 0.01). Synaptophysin immunoreactivity was decreased in LPS group compared with the other groups ( p < 0.05). We observed that melatonin administration prevents neuronal damage, regulates energy metabolism, and protects synaptic vesicle proteins from sepsis-induced reduction.

Encephalopathy develops following sepsis, which is defined as life-threatening organ failure due to the irregular response of a host to infection. It has high mortality and morbidity rates. In this study, we aimed to investigate the effects of inflammation on brain tissue, and the effects of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline in rats with sepsis. Sepsis was experimentally generated in rats using lipopolysaccharide (LPS). The rats were divided into four groups as control, LPS (10 mg/kg i.p.), bicuculline (1.5 mg/kg bicuculline methiodide s.c.), and LPS + bicuculline. Electrophysiologic recordings and body temperature measurements were completed at the 24th hour after injection, and blood samples were taken for measurements of biochemical parameters. TNF-α, IL-10, and GABA levels were measured using ELISA, and MDA levels were measured using the Bouge method. Tissue imaging was performed with S100-ß, NEUN, and synaptophysin antibodies using immunofluorescence staining. One-way ANOVA and the Tukey test were used in statistical analysis. Inflammatory parameters significantly increased in brain tissue in the LPS group compared with the other groups. The immunofluorescence staining results in brain tissues were as follows: S-100ß involvement increased, and NeuN and synaptophysin involvement decreased in the LPS group. In electrophysiologic recordings, activity consistent with acute non-focal seizures was observed in the LPS group; however, resting status was seen in the other groups. We suggest that bicuculline methiodide may be a prophylactic agent in sepsis, which causes impaired neurotransmitter balance, increased pro-inflammatory cytokines, lipid peroxidation, and decreased anti-inflammatory cytokine levels.