Anti-inflammatory role of obestatin in autoimmune myocarditis.

Obestatin is a popular endogeneous peptide, known to have an autoimmune regulatory effect on energy metabolism and the gastrointestinal system. Studies regarding the anti-inflammatory effects of obestatin are scarce. The aim of this study was to show the anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis in rats. Experimental autoimmune myocarditis was induced in Lewis rats by immunization with subcutaneous administration of porcine cardiac myosin, twice at 7-day intervals. Intraperitoneal pretreatment with obestatin (50 µg/kg) was started before the induction of myocarditis and continued for 3 weeks. The severity of myocarditis was evidenced by clinical, echocardiographic and histological findings. In addition, by-products of neutrophil activation, lipid peroxidation, inflammatory and anti-inflammatory cytokines were measured in serum. Obestatin significantly ameliorated the clinical and histopathological severity of autoimmune myocarditis. Therapeutic effects of obestatin in myocarditis were associated with reduced lipid peroxidation, suppression of polymorphonuclear leukocyte infiltration and enhancement of glutathione synthesis, inhibition of serum inflammatory and activation of anti-inflammatory cytokines. Histopathologically, the left ventricle was significantly dilated, and its wall thickened, along with widespread lymphocytic and histocytic infiltration. The myocardium was severely infiltrated with relatively large mononuclear cells. These histopathological changes were observed in lesser degrees in obestatin-treated rats. This study demonstrated a novel anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis. Consequently, obestatin administration may represent a promising therapeutic approach for myocarditis and dilated cardiomyopathy in the future.

Hepatoprotective effect of ghrelin on carbon tetrachloride-induced acute liver injury in rats.

BACKGROUND & AIMS: Recent studies have revealed that ghrelin may be an antioxidant and antiinflammatory agent. Oxidative stress are considered to play a prominent causative role in the development of various hepatic disorders. We investigated whether ghrelin plays a protective role against carbon tetrachloride (CCl(4))-induced acute liver injury in rats. METHODS: Forty adult male Sprague-Dawley rats were randomly divided into four equal groups as; control, ghrelin, CCl(4) and ghrelin plus CCl(4). Evaluations were made for lipid peroxidation, enzyme activities and biochemical parameters. Pathological histology was also performed. RESULTS: CCl(4) treatment increased plasma and liver tissue malondialdehyde (MDA) content and plasma nitric oxide (NO) level, and decreased erythrocyte and liver tissue superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities when compared to control group. At the same time, CCl(4) treatment increased the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alcaline phosphatase (ALP) activities. By contrast, ghrelin pretreatment reduced plasma and liver MDA content and plasma NO level, and increased erythrocyte and liver tissue SOD, CAT and GPx activities when compared with CCl(4)-treated group. Moreover, both ghrelin alone and ghrelin plus CCl(4) treatment elevated serum glucose level. The CCl(4)-induced histopathological changes were also reduced by the ghrelin pretreatment. CONCLUSION: Our results show that ghrelin can be proposed to protect the liver against CCl(4)-induced oxidative damage in rats, and the hepatoprotective effect may be correlated with its antioxidant and free radical scavenger effects.

Protective role of ghrelin against carbon tetrachloride (CCl4)-induced coagulation disturbances in rats.

Recent data indicate that ghrelin has protective effects in different organs and cell types including the pancreas, heart, and gastrointestinal tract. The purpose of this study was to determine whether ghrelin plays a protective role against CCl4-induced coagulation disturbances in rats. Fourty male Sprague-Dawley rats were equally divided into four groups including group 1 (1 ml physiological saline s.c., for 5 days), group 2 (CCl4, i.p., single dose of 1.6 g/kg), group 3 (ghrelin, s.c., 10 nmol/kg/day, for 5 days) and group 4 (ghrelin, 10 nmol/kg/day, for 5 days plus CCl4, i.p., single dose of 1.6 g/kg on the 5th day). Fibrinogen level, activated partial thromboplastin time (aPTT), prothrombin time (PT), platelet counts and alanine transaminase (ALT) activity were evaluated. The values of PT, aPTT and ALT activity were increased (p < 0.05), while fibrinogen level was decreased (p < 0.05) due to CCl4 treatment alone. Pre-treatment with ghrelin prior to the administration of CCl4 reduced (p < 0.05) PT, aPTT and ALT values and increased (p < 0.05) fibrinogen level when compared with CCl4-treated only group. The results of this study suggest that exogenously administered ghrelin may play a protective role against CCl4-induced coagulation disturbances in rats.

Chlorpyrifos induces cardiac dysfunction in rabbits.

This study was carried out to evaluate the effects of organophosphate (OP) insecticide chlorpyrifos on cardiac morphology and function in rabbits using echocardiography. Twenty New Zealand male rabbits were divided equally into four groups. Rabbits were exposed to chlorpyrifos in drinking water at concentrations of 0, 125, 250 or 375 ppm for 90 days. The comparison among the groups indicated that 375 ppm chlorpyrifos resulted in significant decrease (p<0.05) in heart rate (HR), cardiac output (CO), left ventricular fractional shortening (FS), left ventricular ejection fraction (EF), percentage thickening of left ventricle posterior wall (PWT), and significant increase (p<0.05) in left atrial diameter (LA), left ventricular internal diameter in end diastole (LVIDD), left ventricular end diastolic (EDV) and end systolic volumes (ESV) compared to those of the control group. These results showed that chlorpyrifos induces cardiac dysfunction in rabbits.

Echocardiographic variables in healthy guineapigs anaesthetized with ketamine-xylazine.

Echocardiographic parameters were recorded, measured and statistically analysed on a population of 12 male Hartley albino guineapigs under ketamine-xylazine anaesthesia. Additionally, the effect of body weight on these parameters and the correlation between the parameters were assessed. The mean values of left ventricular internal diameter in end diastole (LVIDD), left ventricular internal diameter in end systole (LVIDS), interventricular septum thickness in diastole (IVSD), interventricular septum thickness in systole (IVSS), left ventricular posterior wall thickness in diastole (LVPWD), left ventricular posterior wall thickness in systole (LVPWS), left atrial diameter (LA), aortic diameter (AO), left ventricular fractional shortening (FS) and left ventricular ejection fraction (EF) were measured or calculated as 6.85+/-0.36, 4.35+/-0.17, 1.75+/-0.31, 2.26+/-0.35, 2.28+/-0.40, 2.80+/-0.58, 4.95+/-0.34, 4.65+/-0.25 mm, 35.62+/-2.62 and 70.87+/-3.01%, respectively. A significant (P<0.01) positive correlation to body weight was found with LVIDD, LVPWD, IVSD, aortic root diameter and LA. Significant correlation was also found between a number of echocardiographic parameters.