ABSTRACT

The aim of the study is to investigate the effect of ghrelin treatment on regulation of cell survival, inflammation and oxidative stress in the rat liver of type-2 diabetes model.

Twenty-one male Sprague-Dawley rats (8-10 weeks old) were divided into three groups: control, type-2 diabetes (T2D) and T2D+Ghrelin (25 μg/kg with intraperitoneal (i.p) injection for two weeks). Type-2 diabetes was induced by feeding 10% fructose solution in drinking water for 2 weeks and followed by a single i.p injection of streptozotocin (40 mg/kg). Control animals received tap water. The liver samples were obtained from rats at the end of experiment. Glutathione (GSH), lipid peroxidation (LPO) and protein carbonyl (PCO) levels were measured in liver tissue. Matrix metalloproteinases (MMP-2 and -9), nuclear factor kappa B (NF-κB), peroxisome proliferatoractivated receptor gamma (PPAR-γ), interleukin 6 (IL-6) and proliferating cell nuclear antigen (PCNA) expressions were determined by immunohistochemical methods.

The number of MMP-2, MMP-9, NF-κB, PPAR-γ and IL-6 immunopositive cells increased in the diabetic rat liver as compared to control. The ghrelin treatment significantly reduced the numbers of MMP-2, MMP-9, NF- κB, PPAR-γ and IL-6 immunopositive cells in diabetic rat liver. However, the number of PCNA immunopositive cells increased in diabetic rats treated with ghrelin. Therapeutic effect of ghrelin was not shown in terms of the biochemical parameters including GSH and LPO but PCO levels decreased in the liver.

According to our findings, ghrelin treatment could prevent diabetes-induced inflammation in the liver. However, this treatment did not adequately affect oxidative stress in diabetic rats.