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

Abstract

We aimed to investigate the effects of exogenous ghrelin on cytokine and ghrelin levels, oxidant parameters, and apoptotic genes in lung tissue during sepsis. 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. 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. 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. 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).