Comparative effects of pravastatin and rosuvastatin on carbohydrate metabolism in an experimental diabetic rat model.

Statin treatment may increase the risk of diabetes; there is insufficient data on how statins affect glucose regulation and glycemic control and the effects of statins on liver enzymes related to carbohydrate metabolism have not been fully studied. Therefore, we aimed to compare the effects of the statin derivatives, pravastatin, and rosuvastatin, on carbohydrate metabolism in an experimental diabetic rat model. Female Wistar albino rats were used and diabetes was induced by intraperitoneal injection of streptozotocin. Thereafter, 10 and 20 mg kg-1 day-1 doses of both pravastatin and rosuvastatin were administered by oral gavage to the diabetic rats for 8 weeks. At the end of the experiment, body masses, the levels of fasting blood glucose, serum insulin, insulin resistance (HOMA-IR), liver glycogen, and liver enzymes related to carbohydrate metabolism were measured. Both doses of pravastatin significantly in creased the body mass in diabetic rats, however, rosuvastatin, especially at the dose of 20 mg kg-1 day-1 reduced the body mass signi ficantly. Pravastatin, especially at a dose of 20 mg kg-1 day-1, caused significant increases in liver glycogen synthase and glucose 6-phosphate dehydrogenase levels but significant decreases in the levels of glycogen phosphorylase, lactate dehydrogenase, and glucose-6-phosphatase. Hence, pravastatin partially ameliorated the adverse changes in liver enzymes caused by diabetes and, especially at the dose of 20 mg kg-1 day-1, reduced the fasting blood glucose level and increased the liver glycogen content. However, rosuvastatin, especially at the dose of 20 mg kg-1 day-1, significantly reduced the liver glycogen synthase and pyruvate kinase levels, but increased the glycogen phosphorylase level in diabetic rats. Rosuvastatin, 20 mg kg-1 day-1 dose, caused significant decreases in the body mass and the liver glycogen content of diabetic rats. It can be concluded that pravastatin, especially at the dose of 20 mg kg-1 day-1 is more effective in ameliorating the negative effects of diabetes by modulating carbohydrate metabolism.

Influence of coumarin and some coumarin derivatives on serum lipid profiles in carbontetrachloride-exposed rats.

In the present study, coumarin and some coumarin derivatives (esculetin, scoparone, and 4-methylumbelliferone) were investigated for their lipid-lowering effect in rats. Male Sprague-Dawley rats (150-200 g) were divided into six groups and each group comprised of five rats. Hepatic injury-dependent hyperlipidemia was induced by carbon tetrachloride (CCl4, 1.25 ml/kg). Coumarin and coumarin derivatives esculetin (35 mg/kg), scoparone (35 mg/kg), 4-methylumbelliferone (35 mg/kg), or coumarin (30 mg/kg) were administered to experimental groups at 12-h intervals. Animals received the derivatives esculetin, scoparone or 4-methylumbelliferone prior to the administration of a single toxic dose of CCl4. Serum total cholesterol (TC), triglyceride (TG), very low-density lipoprotein cholesterol (VLDL-C), and low-density lipoprotein cholesterol (LDL-C) levels significantly increased in CCl4-treated group ( p < 0.05, p < 0.01, p < 0.01, and p < 0.05, respectively), while levels of serum high-density lipoprotein cholesterol (HDL-C) decreased ( p < 0.01). 4-Methylumbelliferone had no recovery effects on serum TC levels, however, significantly prevented CCl4-induced hyperlipidemia by reducing TG and VLDL-C levels ( p < 0.05 and p < 0.05, respectively). In addition, coumarin had no recovery effect on any of the serum lipid parameters against CCl4-induced hyperlipidemia. Among the coumarin derivatives only esculetin and scoparone significantly prevented serum HDL-C in CCl4-induced dyslipidemia. The results from this study indicate that the chemical structure of coumarins plays an important role on the regulation of serum lipid profiles.

Comparison of the anti-diabetic effects of resveratrol, gliclazide and losartan in streptozotocin-induced experimental diabetes.

AIM: The aim of this study was to compare the effect of the resveratrol with gliclazide and losartan in streptozotocin induced diabetic rats. MATERIALS AND METHODS: Adult male Wistar albino rats were divided into five groups of seven rats each. Diabetes was induced with a single intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg). Rats with blood glucose levels above 250 mg/dl after 48 h of streptozotocin injection were included in the diabetic group. Gliclazide and resveratrol were administered for 3 weeks at 5 mg/kg per day and losartan was administered for 3 weeks at 30 mg/kg per day in an oral aqueous suspension. At the end of the third week all rats were euthanized and fasting blood glucose, HbA1c and the metabolic activity of the hepatic enzymes hexokinase and glucose-6 phosphate dehydrogenase were measured in tail blood and liver specimens. All parameters were quantified using an ELISA plate reader. RESULTS: Resveratrol and gliclazide significantly reduced both blood glucose levels and HbA1c levels in diabetic rats (p < 0.001). However, losartan did not exhibit the same effects (p < 0.05). The enzymatic activity of the liver enzymes hexokinase, glucose-6 phosphate dehydrogenase, fructose 1,6-biphosphatase, pyruvate kinase and glucose-6 phosphatase were enhanced by resveratrol and gliclazide, while losartan treatment was not associated with significant changes in liver carbohydrate metabolism. CONCLUSION: Resveratrol was not effective in improving liver carbohydrate metabolism relative to gliclazide, a drug widely used to treat diabetes. Dose-response profile of resveratrol remains indeterminate and additional studies may be necessary to determine effective dosing in diabetes.

Blastocystosis in patients with gastrointestinal symptoms: a case-control study.

BACKGROUND: Blastocystosis is a frequent bowel disease. We planned to to evaluate the prevalence of Blastocystis spp. in patients who applied to the same internal medicine-gastroenterology clinic with or without gastrointestinal complaints to reveal the association of this parasite with diagnosed IBS and IBD. METHODS: A total of 2334 patients with gastrointestinal symptoms composed the study group, which included 335 patients with diagnosed inflammatory bowel disease and 877 with irritable bowel syndrome. Patients without any gastrointestinal symptoms or disease (n = 192) composed the control group. Parasite presence was investigated by applying native-Lugol and formol ethyl acetate concentration to stool specimens, and trichrome staining method in suspicious cases. RESULTS: Blastocystis spp. was detected in 134 patients (5.74%) in the study group and 6 (3.12%) in the control group (p = 0.128). In the study group, Blastocystis spp. was detected at frequencies of 8.7% in ulcerative colitis (24/276), 6.78% in Crohn's disease (4/59), 5.82% in irritable bowel syndrome (51/877), and 4.9% in the remaining patients with gastrointestinal symptoms (55/1122). Blastocystis spp. was detected at a statistically significant ratio in the inflammatory bowel disease (odds ratio [OR] = 2.824; 95% confidence interval [CI]: 1.149-6.944; p = 0.019) and ulcerative colitis (OR = 2.952; 95% CI: 1.183-7.367; p = 0.016) patients within this group compared to controls. There were no statistically significant differences between the control group and Crohn's disease or irritable bowel syndrome patients in terms Blastocystis spp. frequency (p = 0.251, p = 0.133). CONCLUSIONS: Blastocystosis was more frequent in patients with inflammatory bowel disease, especially those with ulcerative colitis. Although symptomatic irritable bowel syndrome and Crohn's disease patients had higher rates of Blastocystis spp. infection, the differences were not significant when compared to controls.

Protective effects of coumarin and coumarin derivatives against carbon tetrachloride-induced acute hepatotoxicity in rats.

The comparison of the antioxidant activity of some coumarins with their molecular structure is well determined. However, the protective function of coumarins with various chemical structures against liver toxicity has not yet been well established. Therefore, the aim of this study was to evaluate the possible cytoprotective properties of coumarin and some coumarin derivatives against CCl(4) (carbon tetrachloride)-induced hepatotoxicity. Coumarin (1,2-benzopyrone) and coumarin derivatives esculetin (6,7-dihydroxycoumarin), scoparone (6,7-dimethoxycoumarin) and 4-methylumbelliferone (7-hyroxy-4-methyl) were examined for their protective effect against CCl(4)-induced hepatotoxicity in Male Sprague-Dawley rats. A single toxic dose of CCl(4) (1.25 ml kg(-1), orally) produced liver damage in rats, seen histologically as centrilobular necrosis. Administration of CCl(4) increased serum enzyme levels of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP). Pre-treatment of rats with esculetin (31.15 mg kg(-1), orally) and scoparone (35 mg kg(-1), orally) significantly prevented CCl(4)-induced increase in serum enzymes, whereas 4-methylumbelliferone (35 mg kg(-1)) and coumarin (30 mg kg(-1)) had no effect against CCl(4)-induced rise in serum enzymes. Morphological findings were consistent with the plasma transaminase observations. Among the coumarin analogs, esculetin, which possesses orthodihydroxy coumarins, showed the strongest protective effect against CCl(4)-induced liver damage, followed by scoparone, 4-methylumbelliferone and coumarin, respectively. The results of this study indicate that the chemical structures of coumarins play an important role in the prevention of liver toxicity.

Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model.

It has been suggested that free oxygen radicals play a role in the genesis of epilepsy and in post-seizure neuronal death. The aim of this study was to investigate the dose dependent effect of ghrelin on pentylenetetrazole (PTZ)-induced oxidative stress in a rat seizure model. For this purpose, the ghrelin groups were treated with intraperitoneal injections of ghrelin at doses of 20, 40, 60 and 80 microg/kg before the PTZ injection. Superoxide dismutase (SOD) and catalase (CAT) activities, and reduced glutathione (GSH) and thiobarbituric acid-reactive substance (TBARS) levels were measured in erythrocytes, liver and brain tissue. TBARS, the indicator of lipid peroxidation, was significantly increased in erythrocytes, liver and brain tissue, while antioxidant enzyme activities and glutathione levels were significantly decreased in PTZ injected rats. Ghrelin pretreatment prevented lipid peroxidation and the reduction in antioxidant enzyme activities and GSH levels against PTZ-induced oxidative stress in a dose dependent manner. The present data indicates that PTZ at a convulsive dose induces an oxidative stress response by depleting the antioxidant defense systems and increasing lipid peroxidation in the erythrocytes, liver and brain of rats. Ghrelin pretreatment diminished oxidative stress and prevented the decrease in antioxidant enzyme activities, and thus may reduce neuronal death in the brain during seizures. However, further studies are needed in order to confirm our hypothesis.

Effect of ghrelin on gastric myoelectric activity and gastric emptying in rats.

Ghrelin is a recently discovered peptide in the endocrine cells of the stomach, which may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not been clearly defined. The purpose of this study was to investigate the pharmacological effects of ghrelin on gastric myoelectrical activity and gastric emptying in rats, and to investigate whether cholinergic activity is involved in the effects of ghrelin. The study was performed on Sprague-Dawley rats implanted with serosal electrodes for electrogastrographic recording. Gastric slow waves were recorded from fasting rats at baseline and after injection of saline, ghrelin, atropine, or atropine+ghrelin. Gastric emptying of non-caloric liquid was measured by the spectrophotometric method in conscious rats. Intravenous administration of rat ghrelin (20 microg/kg) increased not only dominant frequency, dominant power and regularity of the gastric slow wave but also the gastric emptying rate when compared with the control rats (P<0.01, P<0.05, P<0.05, P<0.001 respectively). These stimulatory actions of ghrelin on both gastric myoelectrical activity and gastric emptying were not fully eliminated by pretreatment with atropine sulphate. These results taken together suggest that ghrelin may play a physiological role in the enteric neurotransmission controlling gastric contractions in rats.

Antiepileptic effects of ghrelin on pentylenetetrazole-induced seizures in rats.

It is well known that neuropeptide Y (NPY) and gamma-aminobutyric acid (GABA) exert antiepileptic effects in animal models. It has recently been shown that ghrelin neurons increase the activities of GABA and NPY in the brain. Therefore it can be said that ghrelin is an antiepileptic agent. In this study we aimed to investigate the antiepileptic effect of ghrelin in an acute experimental epilepsy model in pentylenetetrazole (PTZ) injected rats. Adult male Wistar albino rats were divided into a control group and four experimental groups with seven rats in each group. In order to generate epileptic seizures, PTZ (50mg/kg) was injected intraperitoneally. The experimental groups received intraperitoneal injections of ghrelin at doses of 20, 40, 60 and 80microg/kg 30min before PTZ injection. After PTZ injection, the latencies were separated into three components: first myoclonic jerk, generalized clonic seizures and tonic generalized extension. The injection of 50mg/kg PTZ-induced epileptic seizures in the control group. The onset times of the three characteristic behavioral changes were significantly delayed and the duration of tonic generalized extension was diminished by dose-dependent ghrelin administration. Our results demonstrated that ghrelin suppresses the onset time of PTZ-induced seizures. In the light of our current knowledge, it seems that ghrelin may be considered as an antiepileptic drug.

Effect of ghrelin administration on phagocytic activity in acute cold-restraint stress exposed rats.

Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, was identified in the rat stomach. This peptide acts through nitric oxide (NO) by expressing endothelial nitric oxide synthase (eNOS) and down regulating inducible nitric oxide synthase (iNOS) at its gastroproprotective effect against restraint stress induced damage. Recently the ghrelin receptor has also been detected in peripheral systems including immune tissue. We have investigated the possible effect of ghrelin on phagocytic activity of peritoneal macrophages in acute cold-restraint stress (ACRS) exposed rats. The rats were divided into control, stress and ghrelin groups. In ghrelin groups, single dose and three days consecutive dose of ghrelin (20 microg/kg. i.p.) were applied to rats that were exposed to ACRS for 4 h. 1 ml of saline was injected i.p. after ACRS for 3 consecutive days to the rats of the stress groups. Ghrelin administration reduced the increased phagocytic activity induced by ACRS. We conclude that ghrelin exerts an important role at macrophage phagocytic activity in ACRS exposed rats.