Investigation of the effectiveness of ghrelin treatment in lung tissue of rats with sepsis.

OBJECTIVE: We aimed to investigate the effects of exogenous ghrelin on cytokine and ghrelin levels, oxidant parameters, and apoptotic genes in lung tissue during sepsis. BACKGROUND: There was evidence that changes of apoptosis are linked with morbidity and mortality in sepsis. There were scarce studies on the effect of ghrelin on apoptotic genes and endogenous ghrelin levels during sepsis. METHODS: Male Wistar albino rats 200-250 g were separated into four groups; Control, LPS (5 mg/kg), Ghrelin (10 nmol/kg i.v.), and LPS+Ghrelin. Tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and ghrelin levels were determined from lung tissue using enzyme-linked immunosorbent assay (ELISA). TNF-α, IL-10, Bcl-2, and Bax gene expressions were calculated using quantitative real-time polymerase chain reaction (RT-PCR), tissue superoxide dismutase enzyme (SOD) activities and malondialdehyde (MDA) were determined spectrophotometerically. RESULTS: TNF-α levels decreased in the LPS+Ghrelin group compared with the LPS (p < 0.001). IL-10 and MDA levels were found highly significantly increased in the LPS and LPS+Ghrelin groups (p < 0.05). Tissue SOD activities were higher in the Ghrelin and LPS+Ghrelin group compared with the LPS (p < 0.05). TNF-α, and Bax expression levels were increased in the LPS compared with the other groups. IL-10 expression levels were increased in the experimental groups compared with the controls. Bcl-2 expression levels were increased in the Ghrelin and LPS+Ghrelin compared with other groups. CONCLUSION: Ghrelin treatment attenuated LPS-induced lung injury. Treatment with ghrelin had no impact on serum and tissue ghrelin levels, but it decreased the level of proinflammatory cytokines. We found that ghrelin treatment had an antioxidant effect on SOD levels. Also, ghrelin decreased the activity of proapoptotic Bax and increased antiapoptotic Bcl-2. Our findings suggest that administration of ghrelin may attenuate damage in lung tissue during sepsis (Fig. 4, Ref. 33).

The impact of pretreatment with simvastatin on kidney tissue of rats with acute sepsis.

It has been reported that changes in cytokine levels affect mitochondrial functions, levels of hypoxia-inducible factor α (HIF-1α), and tissue damage during sepsis. We aimed to investigate the effects of simvastatin pretreatment on mitochondrial enzyme activities, and on levels of ghrelin, HIF-1α, and thiobarbituric acid reactive substances (TBARS) in kidney tissue during sepsis. Rats were separated into four groups, namely, control, lipopolysaccharides (LPS) (20 mg/kg), simvastatin (20 mg/kg), and simvastatin + LPS. We measured the levels of mitochondrial enzyme activities and TBARS in the kidney using spectrophotometry. The histological structure of the kidney sections was examined after staining with hematoxylin and eosin. Tumor necrosis factor α (TNF-α), IL-10, HIF-1α, and ghrelin immunoreactivity were examined using proper antibodies. In tissue, TNF-α (p < 0.01) and HIF-1α (p < 0.05) levels were increased in the simvastatin + LPS and LPS groups. TBARS levels were higher in the LPS group than in the other groups (p < 0.01), but they were similar in the simvastatin + LPS and control groups (p > 0.05). Ghrelin immunoreactivity was lower in the LPS group (p < 0.05) and higher in the simvastatin + LPS group than in the LPS group (p < 0.01). We observed tubular damage in the sections of the LPS group. There were no differences in mitochondrial enzyme activities between the groups (p > 0.05). We observed that pretreatment of simvastatin caused favorable changes on ghrelin and TBARS levels in rats with sepsis.

Amelioration of energy metabolism by melatonin in skeletal muscle of rats with LPS induced endotoxemia.

In the literature, few studies have investigated the effects of melatonin on energy metabolism in skeletal muscle in endotoxemia. We investigated the effects of melatonin on tissue structure, energy metabolism in skeletal muscle, and antioxidant level of rats with endotoxemia. We divided rats into 4 groups, control, lipopolysaccharide (LPS) (20 mg/kg, i.p., single dose), melatonin (10 mg/kg, i.p., three times), and melatonin + LPS. Melatonin was injected i.p. 30 min before and after the 2nd and 4th hours of LPS injection. Antioxidant status was determined by glutathione (GSH) measurement in the blood. Muscle tissue was stained using modified Gomori trichrome (MGT), succinic dehydrogenase (SDH), and cytochrome oxidase (COX) and histological scored. Also the sections were then stained with hematoxylin and eosin. The stained sections were visualized and photographed. Creatine, creatine phosphate, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels were investigated using high performance liquid chromatography (HPLC) in muscle tissue. In the Melatonin + LPS group, blood GSH levels were increased compared with the LPS group (P<0.01). Melatonin reduced myopathic changes in the LPS group according to the histopathologic findings. In addition, ATP values were increased compared with the LPS group (P<0.05). Our findings showed melatonin treatment prevented muscle damage by increasing ATP and GSH levels in rats with LPS induced endotoxemia.