Ozlem Yavuz

The protective effect of curcumin administration on carbon tetrachloride (CCl4)-induced nephrotoxicity in rats

BACKGROUNDnThe aim of the present study was to examine the protective effect of curcumin (CUR) on carbon tetrachloride (CCl4)-induced nephrotoxicity to evaluate the detailed mechanisms by which CUR exerts its protective action.nnnMETHODSnThirty male Wistar-Albino rats weighing 250-300 g were randomly divided into three groups: administrations of olive oil (control, po), CCl4 (0.5mg/kg in olive oil sc) every other day for 3 weeks, and CCl4 (0.5mg/kg in olive oil sc) plus CUR (200mg/kg) every day for 3 weeks.nnnRESULTSnAdministration of CCl4 significantly (p<0.001) increased the levels of renal function test such as creatinine and blood urea nitrogen (BUN). Furthermore, treatment of CCl4 significantly elevated the oxidant status of renal tissues while decreasing its anti-oxidant status (p<0.001). CUR displayed a renal protective effect as evident by significant decrease in inflammation and apoptosis during histopathological examination. The administration of CCl4 resulted in an increase in malondialdehyde (MDA) production due to an increase in membrane lipid peroxidation; however, the administration of CUR attenuated this, probably via its antioxidant and free radical scavenging properties.nnnCONCLUSIONnThe finding of our study indicates that CUR may have an important role to play in protecting the kidney from oxidative insult.

Simvastatin reduces VEGF and NO levels in acute stages of experimental traumatic brain injury

This study was undertaken to evaluate the effect of simvastatin, a cholesterol-lowering agent, on vascular endothelial growth factors (VEGFs), nitric oxide (NO) levels and neuroprotection, in rats with experimentally induced traumatic brain injury (TBI). Forty Wistar albino rats were categorized into four groups: sham operated (S), trauma (T), traumaxa0+xa0vehicle (Txa0+xa0V) and traumaxa0+xa0simvastatin (Txa0+xa0S). The T, Txa0+xa0V and Txa0+xa0S groups were subjected to TBI. The Txa0+xa0V group was administered vehicle [ethanol:saline (1/2)] and the Txa0+xa0S group was administered 1xa0mg/kg of simvastatin 3xa0h after the injury insult. Blood and brain tissue specimens were obtained 24xa0h after the trauma to measure VEGFs and NO levels and perform histopathological examinations. The histopathological injury scores of brain tissues were significantly higher in the T group, and simvastatin significantly prevented brain injury in the Txa0+xa0S group. In the T group, significant increases of VEGF levels in serum and brain tissues were noted, which were prevented with simvastatin treatment in the Txa0+xa0S group. The markedly high levels of NO in brain tissues of the T group were decreased by simvastatin treatment in the Txa0+xa0S group. It can be concluded that, as evidenced by histopathological findings, simvastatin treatment improves neuropathology in acute stages of TBI.

Experimental acute myocardial infarction in rats: HIF-1α, caspase-3, erythropoietin and erythropoietin receptor expression and the cardioprotective effects of two different erythropoietin doses.

The cardioprotective effects of two different doses of erythropoietin administration were analyzed in rats with experimental myocardial infarction. None, saline, standard-dose (5000Ukg(-1)) and high-dose (10,000Ukg(-1)) of human recombinant erythropoietin alpha were administered intraperitoneally in Wistar rats with myocardial infarction induced by coronary artery ligation. Infarct sizes measured after triphenyltetrazolium chloride staining, levels of biochemical markers, histopathology examined by light and electron microscopy, and immunohistochemical expressions of erythropoietin, erythropoietin receptor, hypoxia inducible factor-1α and caspase-3, were analyzed. Lower scores of infarction and hemorrhage, lower number of macrophages and higher score of vascularization surrounding the infarct area were observed in the erythropoietin administered groups (p<0.05). Erythropoietin administration after myocardial infarction reduced the area of infarction and hemorrhage. There were hypoxia inducible factor-1α and caspase-3 expressions in the marginal area, and erythropoietin and erythropoietin receptor expression in both marginal and normal areas (p<0.001). Vascularization, erythropoietin expression in the normal area and vascular erythropoietin expression were positively correlated with human erythropoietin levels. The cardioprotective effects of erythropoietin treatment were independent of endogenous erythropoietin/erythropoietin receptor activity. Moreover exogenous erythropoietin treatment did not suppress endogenous erythropoietin. Erythropoietin administration after myocardial infarction reduced caspase 3 expression (apoptotic activity) and induced neovascularization around the infarct area. Higher erythropoietin administration did not provide an additional benefit over the standard-dose in myocardial protection.

Pyrrolidine dithiocarbamate attenuates the development of monocrotaline-induced pulmonary arterial hypertension

We aimed to demonstrate the potential protective effects of pyrrolidine dithiocarbamate (PDTC) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Adult male rats were randomly assigned to 4 groups: control group, MCT-treated rats only, MCT-injected rats treated with PDTC, and PDTC-treated rats only. Blood and tissue samples were collected after the sacrifice. Levels of malondialdehyde (MDA) were measured by using the thiobarbituric acid method. Total antioxidant status (TAS) was determined using a commercially available ImAnOx kit. A histopathological evaluation was accomplished by scoring the degree of severity. Endothelial damage of the main pulmonary artery was evaluated by immunohistochemical labeling of endothelial cells using anti-rat endothelial cell antigen 1 (RECA-1) antibody. MCT-induced right ventricular hypertrophy (RVH) was reduced significantly in the MCT+PDTC-treated group. MDA levels were significantly lowered in the MCT+PDTC-treated group. TAS was significantly higher in the MCT+PDTC-treated group when compared with the rats with PAH. Histopathological examination demonstrated that PDTC treatment reduced the development of inflammation, hemorrhage and congestion, and collagen deposition. In conclusion, PDTC attenuated PAH and protected pulmonary endothelium in rats administered MCT. These findings suggest that PDTC treatment may provide a new effective therapeutic approach in the treatment of PAH.

Histopathological changes in rat pancreas and skeletal muscle associated with high fat diet induced insulin resistance

The effects of a high fat diet on the development of diabetes mellitus, insulin resistance and secretion have been widely investigated. We investigated the effects of a high fat diet on the pancreas and skeletal muscle of normal rats to explore diet-induced insulin resistance mechanisms. Forty-four male Wistar rats were divided into six groups: a control group fed standard chow, a group fed a 45% fat diet and a group fed a 60% fat diet for 3 weeks to measure acute effects; an additional three groups were fed the same diet regimens for 8 weeks to measure chronic effects. The morphological effects of the two high fat diets were examined by light microscopy. Insulin in pancreatic islets was detected using immunohistochemistry. The homeostasis model assessment of insulin resistance index and insulin staining intensity in islets increased significantly with acute administration of high fat diets, whereas staining intensity decreased with chronic administration of the 45% fat diet. Islet areas increased significantly with chronic administration. High fat diet administration led to islet degeneration, interlobular adipocyte accumulation and vacuolization in the pancreatic tissue, as well as degeneration and lipid droplet accumulation in the skeletal muscle tissue. Vacuolization in the pancreas and lipid droplets in skeletal muscle tissue increased significantly with chronic high fat diet administration. We suggest that the glucolipotoxic effects of high fat diet administration depend on the ratio of saturated to unsaturated fatty acid content in the diet and to the total fat content of the diet.

Single dose varenicline may trigger epileptic activity.

Varenicline is a new drug for smoking cessation, and its effect on epilepsy is not clear. The aim of this study was to investigate whether different doses of varenicline cause epileptic activity. Forty rats were randomly assigned to the following eight groups: control, saline, and 0.025, 0.04, 0.1, 0.5, 1, and 2xa0mgxa0kg−1 varenicline (single dose, i.p.). EEGs were recorded before the varenicline injection and during the following 240xa0min. While epileptic discharges were observed on the EEGs of the rats in all of the varenicline-treated groups, motor findings of epileptic seizure were not observed in some rats in these groups except the 1 and 2xa0mgxa0kg−1 groups. These findings indicate that different single doses of varenicline cause epileptic activity in rats.

Orexin and adiponectin in high fat diet–induced insulin resistance

ABSTRACT Orexin A (OXA) is a hypothalamic neuropeptide with both central and peripheral activities on insulin signaling and energy balance. Adiponectin is an adipocytokine which regulates metabolisms of lipid and glucose via its receptors AdipoR1 and AdipoR2. This study investigated immunohistochemical changes in expressions of OXA, its receptor OX1R in pancreas and AdipoR1 in skeletal muscle with a high fat diet (HFD)-induced insulin resistance (IR). Standard 45% fat and 60% fat diets were administered to Wistar rats for 3 and 8 w. OXA expression increased with both 3- and 8-w 45% fat diets. OX1R expression also increased with a 3-w 45% fat diet, but decreased with the 3-w 60% fat diet. OXA, OX1R, and AdipoR1 expressions decreased with a 8-w 60% fat diet. An early adaptation in context of OXA was observed in pancreas β-cell to HFD-induced IR. OXA, OX1R, and AdipoR1 expressions decreased with either the higher amount or longer duration of HFD consumption.

The acute effect of commercial "energy drink" on hematological, biochemical and strength parameters induced by eccentric contractions

BACKGROUND: Commercial energy drink usage is reported to be higher in athletes and adolescents. However, the impact of pre-exercise consumption of energy beverages on hematologic and biochemical responses and skeletal muscle contractile properties has not been fully elucidated. METHOD: Ten male subjects performed 50 maximal eccentric actions on an isokinetic dynamometer at 90 ◦ /sec followed by two identical trials that were preceded by consuming either a placebo (P) or energy drink (ED) beverage. The test was repeated after 7–10 days while consuming the alternate beverage. Complete blood counts and chemistry profile was conducted before and immediately after exercise. RESULTS: Eccentric contractions resulted in an increased number of neutrophils (Neut) and decreased lymphocytes (Lymph), decreased eosinophils (EOS) and did not change basophil (BASO) levels in control. However, the BASO levels increased immediately after the exercise with P and ED beverage consumption. In contrast, P and ED beverage consumption had no effect on Neut, Lymph, MONO or EOS counts after exercise compared to pre-exercise values. Acute exercise increased creatinine kinase (CK) and decreased phosphorus (Pi) but did not have any effect on other blood chemistry parameters. The biochemical profile and eccentric muscle contractile properties were not significantly affected by any of the beverages. CONCLUSIONS: Consumption of pre-exercise energy drink does not have a favorable effect on immune blood cells induced in the acute eccentric exercise model.