The role of 5-HT7 receptors on isoproterenol-induced myocardial infarction in rats with high-fat diet exacerbated coronary endothelial dysfunction.

The presence of 5-HT7r's in both human and rat cardiovascular and immune tissues and their contribution to inflammatory conditions prompted us to hypothesize that these receptors contribute in acute myocardial infarction (MI) with underlying chronic endothelial dysfunction. We investigated the role of 5-HT7 receptors on heart tissue that damaged by isoproterenol (ISO)-induced MI in rats with high-fat diet (HFD). In vitro and in vivo effects of 5-HT7r agonist (LP44) and antagonist (SB269970) have been investigated on the H9C2 cell line and rats, respectively. For in vivo analyses, rats were fed with HFD for 8 weeks and after this period ISO-induced MI model has been applied to rat. To investigate the role of 5-HT7r's, two different doses of LP44 and SB269970 were evaluated and compared with standard hypolipidemic agent, atorvastatin. In vitro studies showed that LP44 has protective and proliferative effects on rat cardiomyocytes. Also in in vivo studies stimulating 5-HT7r's by LP44 improved blood lipid profile (decreased total cholesterol, low-density lipoprotein-C, and triglyceride, increased high-density lipoprotein), decreased cardiac damage markers (creatine kinase and troponin-I), and corrected inflammatory status (tumor necrosis factor-α, interleukin-6). Our results showed significant improvement in LP44 administered rats in terms of histopathologic analyses. In damaged tissues, 5-HT7 mRNA expression increased and agonist administration decreased this elevation significantly. We determined for the first time that 5-HT7r's are overexpressed in ISO-induced MI of rats with underlying HFD-induced endothelial dysfunction. Restoration of this overexpression by LP44, a 5-HT7r agonist, ameliorated heart tissue in physiopathologic, enzymatic, and molecular level, showing the cardiac role of these receptors and suggesting them as future potential therapeutic targets.

THE EFFECTS OF VARIOUS DOSES OF PREDNISOLONE ADMINISTRATION ON SERUM VASPIN LEVELS IN RATS.

AIM: The aim of this study was to investigate the dose-dependent effects of prednisolone administration on serum vaspin levels and correlate this with changes in the BMI and lipogenesis in rats. MATERIALS AND METHODS: Twenty-four albino Wistar male rats weighing between 190-240 g were divided into four groups, three experimental (5 mg/kg, 10 mg/kg, and 20 mg/kg prednisolone) and one control. The prednisolone groups were given once-daily doses for 30 days, orally. In addition, the rats were weighed, and their height and waist circumferences were measured once a week. At the end of 30 days, vaspin and glucose levels were measured from blood samples. RESULTS: In the prednisolone groups, the vaspin levels significantly increased when compared with the control group. The control group has a serum vaspin level of 155 ± 20.99 pg/mL and this level has been increased by prednisolone administration in a dose dependent manner. In the prednisolone groups, especially the 10 mg/kg and 20 mg/kg groups, the glucose levels increased in a dose dependent fashion. CONCLUSION: Prednisolone administration significantly increased serum glucose and vaspin levels in a dose dependent manner, indicating that the increase in the serum vaspin levels could be related to the increase in the serum glucose concentration. Vaspin can be a molecule that is released in response to increased glucose and can be a rebound defense mechanism to modulate the blood glucose concentration. We suggest vaspin as a potential target for the treatment and diagnosis of diabetes mellitus and other metabolic disorders.

The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines (HepG2).

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1ß. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.