Effects of ukrain in rats with intestinal ischemia and reperfusion.

BACKGROUND: The purpose of this study is to investigate the potential protective effect of the ukrain on ischemia-reperfusion (IR) injury in rat intestine, which has not previously been studied. METHODS: Thirty-one male Sprague-Dawley rats were randomly assigned to four groups, each consisting of eight rats as follows: (1) a sham group (S) (laparotomy, but no IR injury); (2) ukrain group (U) (no IR, and ukrain was administered intraperitoneally 1 h before laparotomy); (3) intestinal ischemia-reperfusion (II/R) group (30-min occlusion of the superior mesenteric artery then 2-h reperfusion); and (4) ukrain + II/R group (U + II/R) (30-min occlusion of the superior mesenteric artery then 2-h reperfusion; ukrain was administered intraperitoneally 1 h before IR). RESULTS: Serum total oxidant status (TOS) and total antioxidant status (TAS) were measured using Erel method. Oxidative stress index was calculated using the TOS/TAS ratio. TAS levels increased and TOS serum levels were also significantly decreased in the ukrain + IR group compared with the IR group (P = 0.000 and P = 0.015). CONCLUSIONS: In this study, we demonstrated for the first time in literature that ukrain helps to prevent intestinal tissue breakdown against II/R injury and that this effect can be achieved by antioxidant activities.

Protective effects of simvastatin administered in the experimental hepatic ischemia-reperfusion injury rat model.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a major complication in clinical practice. Previous studies suggest that statins have pleiotropic effects in addition to cholesterol-lowering effects. In this study, we aimed to investigate the hepatoprotective role of two different doses of simvastatin (SV) pretreatment in rats with experimental hepatic I/R injury. METHODS: Adult male Sprague-Dawley rats were divided into four groups (n = 7 in each group) :control, I/R, I/R with 2.5-mg/kg SV, and I/R with 5.0-mg/kg SV. Before hepatic I/R was induced, SV was injected intraperitoneally at doses of 2.5 and 5.0 mg/kg. After 45-min ischemia and a 60-min reperfusion period, the animals were euthanized, and liver tissues were excised. Tissue levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase, glutathione peroxidase, and catalase were measured. Liver tissues were also evaluated histopathologically and immunohistochemically. RESULTS: Histopathologic evaluation showed that 5.0-mg/kg SV reduced hepatic damage and apoptosis. Pretreatment with 5.0-mg/kg SV reduced malondialdehyde and nitric oxide levels (P < 0.01) and increased superoxide dismutase, glutathione peroxidase, and catalase activities significantly (P < 0.001, P < 0.01) in I/R with 2.5-mg/kg SV compared with I/R group. In addition, SV decreased Kupffer cell activation, and hypoxia-inducible factor-1α and vascular endothelial growth factor protein levels. CONCLUSIONS: The results of this study suggest that 5.0-mg/kg SV pretreatment may be protective against hepatic I/R injury. This effect can be achieved by antioxidant and antiapoptotic activities.

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 2 mg kg(-1) varenicline (single dose, i.p.). EEGs were recorded before the varenicline injection and during the following 240 min. 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 2 mg kg(-1) groups. These findings indicate that different single doses of varenicline cause epileptic activity in rats.

Blood pressure measurement in freely moving rats by the tail cuff method.

Inconsistency in consecutive blood pressure values is one of the most frequently observed problems in tail cuff method. The aim of this study was to measure blood pressure using the tail cuff method in rats without heating, anesthesia, and movement restriction. In this study, it has been shown that blood pressure measurement could be obtained without problem using the tail cuff method in freely moving rats in their cage environment. Also, the reliability of consecutive blood pressure values obtained from freely moving rats was higher than ether anesthesia and restricted groups.

The effects of in vivo and ex vivo various degrees of cold exposure on erythrocyte deformability and aggregation.

BACKGROUND: This study aimed to investigate alterations in hemorheology by cold exposure, in vivo and ex vivo, and to determine their relationship to oxidative stress. MATERIAL/METHODS: Rats were divided into 2 in vivo and ex vivo cold exposure groups. The in vivo group was further divided into control (AR), AC (4°C, 2 hours) and ALTC (4°C, 6 hours) subgroups; and the ex vivo group was divided into control (BR) and BC (4°C, 2 hours) subgroups. Blood samples were used for the determination of erythrocyte deformability, aggregation, and oxidative stress parameters. RESULTS: Erythrocyte deformability and aggregation were not affected by 2-hour ex vivo cold exposure. While 2 hour in vivo cold exposure reduced erythrocyte deformability, it returned to normal after 6 hours, possibly due the compensation by acute neuroendocrine response. Six hours of cold exposure decreased aggregation index, and might be an adaptive mechanism allowing the continuation of circulation. Aggregation of ex vivo groups was lower compared to in vivo groups. Cold exposure at various temperatures did not cause alterations in plasma total oxidant antioxidant status and oxidative stress index (TOS, TAS, OSI) when considered together. CONCLUSIONS: Results of this study indicate that the alterations observed in hemorheological parameters due to cold exposure are far from being explained by the oxidative stress parameters determined herein.

The effects of docosahexaenoic acid supplementation and exercise on growth hormone and insulin-like growth factor I serum levels during chronic hypoxia in rats.

BACKGROUND: In this study we examined the effects of docosahexaenoic acid (DHA) on growth hormone (GH), insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) in response to chronic hypoxia and exercise training in hypoxic conditions. METHODS: Thirty-five rats were divided into five groups; control group (C), hypoxia group (H), hypoxia-exercise group (HE), hypoxia-docosahexaenoic acid group (HD), hypoxia-exercise-docosahexaenoic acid group (HED). A treadmill exercise was performed as 30 m/min for 20 min/day, 5 days per week for 28 days at level grade for the exercising groups (HE and HED). DHA was given to the HD and HED groups every day orally (36 mg/kg). The animals, except for the C group, were exposed to hypoxia for 28 days. RESULTS: Serum levels of GH and IGF-I in the H group decreased after chronic hypoxia (p<0.001). GH and IGF-I in the HD group also decreased compared with the C group (p<0.05, p<0.01, respectively). GH in C group did not show significant difference compared with the HE and HED groups. Decreased serum level of IGF-I was observed for the HED group (p<0.05). CONCLUSIONS: According to our findings, chronic hypoxia exposure decreases serum levels of GH, and IGF-I and exercise training have a slightly positive effect on GH/IGF-I axis during hypoxia. In addition, DHA supplementation slightly increases GH and IGF-I serum levels in hypoxic conditions. However, this effect on GH/IGF-I axis during hypoxia is not strong compared with exercise. Therefore, we concluded that exercise and/or DHA supplementation does not have additional positive effect on these hormones in hypoxic conditions.

Effects of the hippocampal deep brain stimulation on cortical epileptic discharges in penicillin - induced epilepsy model in rats.

AIM: Experimental and clinical studies have revealed that hippocampal DBS can control epileptic activity, but the mechanism of action is obscure and optimal stimulation parameters are not clearly defined. The aim was to evaluate the effects of high frequency hippocampal stimulation on cortical epileptic activity in penicillin-induced epilepsy model. MATERIAL AND METHODS: Twenty-five Sprague-Dawley rats were implanted DBS electrodes. In group-1 (n=10) hippocampal DBS was off and in the group-2 (n=10) hippocampal DBS was on (185 Hz, 0.5V, 1V, 2V, and 5V for 60 sec) following penicillin G injection intracortically. In the control group hippocampal DBS was on following 8 µl saline injection intracortically. EEG recordings were obtained before and 15 minutes following penicillin-G injection, and at 10th minutes following each stimulus for analysis in terms of frequency, amplitude, and power spectrum. RESULTS: High frequency hippocampal DBS suppressed the acute penicillin-induced cortical epileptic activity independent from stimulus intensity. In the control group, hippocampal stimulation alone lead only to diffuse slowing of cerebral bioelectrical activity at 5V stimulation. CONCLUSION: Our results revealed that continuous high frequency stimulation of the hippocampus suppressed acute cortical epileptic activity effectively without causing secondary epileptic discharges. These results are important in terms of defining the optimal parameters of hippocampal DBS in patients with epilepsy.

The influence of cervical spinal cord stimulation on induced epileptic discharges in rats.

Spinal cord stimulation (SCS), also known as dorsal column stimulation, is a novel technique used widely in pain surgery. However, its effect on other pathologies such as epileptic disorders is unknown. The aim of this study is to evaluate the influence of electrical epidural stimulation of the upper cervical region on epileptic cortical discharges. The long term goal is to elucidate and evaluate a therapeutic central nervous system (CNS) electrical stimulation methodology to treat epilepsy. Twelve Wistar female rats were randomly divided into two groups. In group 1 (six rats under general anesthesia), C2-3 laminectomies were performed and epidural electrodes were placed to perform SCS. To induce epileptic discharges, 1 ml (200 IU) penicillin G was microinjected into the left somatomotor cortex via left stereotactic parietal craniotomies, 0.01 to 0.1 mA at 2 Hz was used to stimulate the spinal cord. In group 2 (the control group, six rats under general anesthesia), C2-3 laminectomies were performed without electrode placement and epileptic discharges were induced with penicillin G microinjections, as described above. Both groups were monitored with digital electroencencephalography (EEG) for 70 min in seven stages and recordings analyzed with power spectral analysis. Spinal cord stimulation decreased penicillin-induced median values of epileptic discharges. Epileptic wave frequencies decreased significantly with increasing intensities of SCS. The results of this study suggest that SCS used for drug resistant epilepsies may be a viable alternative treatment modal.

Angiotensin-converting enzyme polymorphism in healthy young subjects: relationship to left ventricular mass and functions.

OBJECTIVES: Angiotensin-converting enzyme (ACE) is a key enzyme in the production of angiotensin II and thus may participate in the modulation of cardiac growth. The cloning of the ACE gene has made it possible to identify a deletion (D)-insertion (I) polymorphism that appears to affect the level of serum ACE activity. The aim of the study is to analyse the ACE gene I/D polymorphisms in healthy young subjects and to evaluate its relationship to left ventricular mass and functions. METHODS: 38 women and 40 men (mean age 21.1 +/- 1.7 and 21.4 +/- 1.7 years) were studied. They underwent complete echocardiographic assessment and analysis of ACE insertion (I) and deletion (D) allele frequencies in peripheral blood by polymerase chain reaction. Thickness of interventricular septum (IVS) and posterior wall (LVPW) and left ventricular mass (LVM) and LVM index (LVMI) were measured by M-mode. Left ventricular ejection fraction (LVEF) was calculated by Simpson's method. RESULTS: There was no statistically significant difference among the DD, DI and II genotypes, concerning age, body mass index, heart rate, systolic and diastolic blood pressures.The thickness of IVS (9.5 mm), LVPW (9.0 mm), LVM (204.5 g) and LVMI (105.5 g/m2) in DD genotypes were higher than both DI (8.3 mm; 8.1 mm; 168.1 g; 90.9 g/m2) and II genotypes (8.2 mm; 7.0 mm; 141.7 g; 77.8 g/m2) in men, but not in women. LVEF among the 3 genotypes were not statistically different. CONCLUSION: Our findings suggest that left ventricular hypertrophy is partially determined by genetic disposition especially in men but not in women.

Effects of cadmium and zinc on plasma levels of growth hormone, insulin-like growth factor I, and insulin-like growth factor-binding protein 3.

Humans are constantly exposed to cadmium (Cd) as a result of the increase in air pollution and cigaret use. Zinc (Zn), which is an essential element for the metabolism of and the constituent of many enzymes, causes growth retardation in the deficiency status, so at present it is often added to the diet without measuring blood levels of this element. We also aimed to observe the effects of both Cd and Zn on the plasma levels of growth hormone (GH), insulin-like growth factor I (IGF-I), and insulin-like growth factor-binding protein 3 (IGFBP-3) in this study. For this purpose, 27 young Wistar albino male rats were divided into three groups. The first group was given 50 mg/L of CdCl2, the second group received 500 mg/L of ZnSO4, and the third group, as a control, received only drinking water for 1 mo. At the end of this period, plasma GH, IGF-I, and IGFBP-3 of the animals were analyzed in the blood obtained. The significance between groups was evaluated with the Mann-Whitney U-test. According to our results, levels of IGF-I and IGFBP-3 in the Cd-administered group were significantly lower than those of controls (p<0.05 and p<0.01 respectively). No statistically significant difference was observed between Zn-administered and control groups in terms of all three parameters. These results show that although the addition of Zn to the diet of healthy rats had no effect on the levels of GH, IGF-I, and IGFBP-3, Cd addition lowered the levels of IGF-I and IGFBP-3 but did not change the levels of GH compared to controls.

Comparison of the effects on spinal reflexes of acetylsalicylate and metamizol in spinalized and normal rats.

The effects of nonsteroidal antiinflammatory drugs, acetylsalicylate and metamizol, on spinal monosynaptic reflexes were investigated in spinalized and normal rats. Adult rats (n=36) weighing 150-200 g were anesthetized with ketamine and artificially ventilated. Half of rats were spinalized at C1 level. A laminectomy was performed in the lumbosacral region. Following electrical stimulation of the sciatic nerve by single pulses, reflex potentials were recorded from the ipsilateral L5 ventral root. Acetylsalicylate was administered orally (100 mg/kg for both spinalized and normal rats). Metamizol was administered intramuscularly (15 mg/kg for both spinalized and normal rats). These drug administrations significantly decreased the amplitude of reflex response in all groups (p < 0.05). These data verify that observed inhibition by acetylsalicylicate and metamizol may be at the level of spinal cord. Also we suggested that the cyclooxygenase products of arachidonic acid may play an important role in regulating the reflex potential.

Balanced oxidative status by nesfatin-1 in intestinal ischemia-reperfusion.

OBJECTIVE: Ischemia causes reversible or irreversible cell or tissue damage and reperfusion can exaggerate cellular damage. Microvascular dysfunction is induced and causes enhanced fluid filtration in capillaries. At the acute phase of reperfusion more oxygen radicals are activated. Nesfatin-1 protects brain against oxidative damage and heart against ischemia/reperfusion damage. In our study, we aimed to investigate the acute effect of chronic peripheral nesfatin-1 administration in intestinal ischemia/reperfusion created rats. METHOD: Two-months-old, 28 Wistar Albino male rats, weighing an average of 200-250 g, were used and randomly divided into four experimental groups (n=7) as; Laparotomy, Ischemia/Reperfusion, Nesfatin-1+Laparotomy, Nesfatin-1+Ischemia/Reperfusion. Serum levels of total oxidant status (TOS) and total antioxidant status (TAS) were determined by colorimetric measurement method. The plasma levels of endotelin-1 and endothelial nitric oxide syntheses (eNOS) were analyzed by rat ELISA assay kits. RESULTS: Plasma levels of endothelin-1 significantly increased, plasma level of eNOS, serum levels of TOS and TAS significantly decreased in nesfatin-1 applied groups. Additionally, The oxidative stress index (OSI) parameters decreased significantly in three groups compared to laparotomy. CONCLUSION: Chronic peripheral nesfatin-1 administration can decrease eNOS level and OSI at the acute phase of ischemia/reperfusion. We suppose that it can be protective for ischemia/reperfusion injury by balancing oxidant capacity. On the other hand, this effect of nesfatin-1 is not related with micro-circular compensation and increases anti-oxidant capacity.

Evaluation of multidrug resistance-1 gene C>T polymorphism frequency in patients with asthma.

OBJECTIVES: Asthma is a chronic inflammatory lung disease characterized by bronchial hyperresponsiveness and airflow obstruction. Genetic and oxidative stress factors, in addition to pulmonary and systemic inflammatory processes, play a pivotal role in the pathogenesis of asthma. The products of the multidrug resistance-1 gene protect lung tissue from oxidative stress. Here, we aimed to evaluate the association between the multidrug resistance-1 gene C>T polymorphism and asthma with regard to oxidative stress-related parameters of asthmatic patients. METHODS: Forty-five patients with asthma and 27 healthy age-matched controls were included in this study. Blood samples were collected in tubes with ethylenediaminetetraacetic acid. DNA was extracted from the blood samples. The multidrug resistance-1 gene polymorphism was detected by polymerase chain reaction and a subsequent enzyme digestion technique. The serum levels of total oxidant status and total antioxidant status were determined by the colorimetric measurement method. RESULTS: The heterozygous polymorphic genotype was the most frequent in both groups. A significant difference in the multidrug resistance-1 genotype frequencies between groups indicated an association of asthma with the TT genotype. A significant difference between groups was found for wild type homozygous participants and carriers of polymorphic allele participants. The frequency of the T allele was significantly higher in asthmatic patients. The increase in the oxidative stress index parameter was significant in the asthma group compared with the control group. CONCLUSIONS: The multidrug resistance-1 gene C/T polymorphism may be an underlying genetic risk factor for the development of asthma via oxidant-antioxidant imbalance, leading to increased oxidative stress.

The effect of ozone on blood pressure in DOCA-salt-induced hypertensive rats.

BACKGROUND: Hypertension is a risk factor for the cardiovascular diseases. Ozone as a therapeutic agent for the treatment of several disorders. We aimed to observe the effects of ozone on the blood pressure in DOCA-salt hypertensive rats. METHODS: Twenty three young Sprague Dawley male rats were divided into three groups; Control (C), Hypertension (H) and Hypertension + Ozone (HO). Hypertension was induced by injection of DOCA-salt (25 mg/kg, s.c.) twice weekly, 4 weeks, whereas intraperitoneal ozone was administered (1.1 mg/kg) for 10 days. Serum endothelin-1, nitric oxide and renin levels were measured with ELISA. Blood pressures were monitored using a tail cuff system. Endothelin-1, ET receptor A and ET receptor B mRNA expression in heart and vascular tissue were assessed by quantitative reverse transcription polymerase chain reaction. RESULTS: Blood pressure, serum endothelin-1 and ET receptor A mRNA expression levels were increased in H group, whereas serum renin, nitric oxide and ET receptor B mRNA expression levels in the heart and vascular tissue decreased compared with C and HO groups, which were counteracted by ozone treatment. CONCLUSION: Ozone treatment decreases blood pressure and is effective in preventing the progression of hypertensive disease, the mechanisms of which are associated with anti-vasoconstrictor effects through reducing the levels of serum endothelin-1 and ET receptor A mRNA expression in the heart and vascular tissue.

Characterization of the apelin -1860T>C polymorphism in Turkish coronary artery disease patients and healthy individuals.

To evaluate the association between the apelin -1860T>C polymorphism and plasma apelin levels in Turkish patients with coronary artery disease (CAD). A total of 276 individuals were enrolled in the present study, including 158 patients with CAD and 118 individuals without CAD as controls. The presence of the apelin -1860T>C gene polymorphism and plasma apelin levels were determined using polymerase chain reaction/restriction fragment length polymorphism and enzyme-linked immunosorbent assay, respectively. Significance was set at p≤0.05 for all statistical analyses. The genotype and allele frequencies of interested genes were significantly different between groups (χ(2)=10.2; df=2; p=0.006 and χ(2)=13.4; df=1; p=0.000, respectively). Frequency of CC genotype and the C allele of -1860T>C site was significantly higher in CAD patients compared to healthy controls. We found that individuals with the TC and CC genotypes were associated with an increased risk of CAD when compared with the TT genotype in CAD patients, and the adjusted ORs (95% CI) were 6.50 (1.27-33.0) and 6.39 (1.77-23.0), respectively. Plasma apelin levels were significantly lower in CAD patients compared to control group. Apelin level of CAD patient group having CC genotype of -1860T>C site was significantly lower compared to those having TT genotypes, but it was not statistically significant (p > 0.05). The homozygous CC genotype of apelin gene is associated with high risk of CAD. Apelin gene polymorphism -1860T>C is a significant predictor of predisposition to CAD in in Turkish population.

APJ receptor A445C gene polymorphism in Turkish patients with coronary artery disease.

Coronary artery disease (CAD) is a disease in which a waxy substance called plaque builds up inside the coronary arteries. Apelin is a novel endogenous peptide with inotropic and vasodilatory properties and is the ligand for the angiotensin receptor-like 1 (APJ) receptor. We aimed to determine genotype and allele frequencies of APJ receptor A445C gene polymorphism in Turkish patients with CAD and healthy controls by RFLP-PCR. This study was performed on 159 unrelated CAD patients and 62 healthy controls. We obtained AA, AC and CC genotype frequencies in CAD patients as 41.5%, 49.1% and 9.4%, respectively. In the control group, frequencies of genotypes were found as 35.5% for AA, 48.4% for AC and 16.1% for CC. We did not observe difference in APJ receptor A445C polymorphism between CAD patients and healthy controls (χ(2) = 2.178; df = 2; P = 0.336). The A allele was encountered in 66% (210) of the CAD and 59.7% (74) of the controls. The C allele was seen in 34% (108) of the CAD and 40.3% (50) of the controls. Allele frequencies of interested genes were not significantly different between groups (χ(2) = 1.57; df = 1; p = 0.225). The frequencies of APJ receptor A445C genotype were not significantly different between control and patients. None of the three APJ receptor A445C genotypes, AA, AC and CC displayed significant difference in CAD patients. We did not find any difference in the clinical parameters except for weight and diastolic blood pressure levels in the AA, AC and CC genotypes of patients. Individuals with CC genotypes had significantly higher weight, systolic and diastolic blood pressure levels and systolic blood pressure than other genotypes, P ≤ 0.05. In addition, HDL-C level was found decreased, but this reduction was not statistically significant. Contrarily, the low levels of weight, SBP, DBP and TC were statistically significant in the subjects with AA genotype in CAD. In conclusion, CC genotype carriers may have more risk than other genotypes in the development of hypertension in CAD, but not AAgenotype carriers. We suggest that this polymorphism may not be a marker of CAD, but it may cause useful in function of the apelin/APJ system and may be a genetic predisposing factor for diagnostic processes and can be helpfull in finding new treatment strategies. We think that it is required to further comprehensive studies in order to make clear this situation in CAD.

Angiotensinogen gene M235T and angiotensin II-type 1 receptor gene A/C1166 polymorphisms in chronic obtructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) occurs irreversibly and is characterized by progressive airflow obstruction. Renin angiotensin system (RAS) has many different key enzymes and receptors that have a role for different systemic processes. We aimed to determine genotype and allele frequencies of angiotensinogen (AGT) M235T and angiotensin II-type 1 receptor (AT1-R) A/C1166 polymorphisms in patients with COPD. This study was performed on 56 unrelated COPD patients and 29 healthy subjects. DNA samples for each individual were isolated from peripheral blood by phenol/chloroform method, analyzed by polymerase chain reaction and enzymatic digestion methodologies. The distribution for each of AGT genotypes were 23.2% for MM (13), 75.0% for MT (42) and 1.8% for TT (1) in the COPD group; 37.9% for MM (11), 34.5% for MT (10) and 27.6% for TT (8) in the control group. The distribution of AGT genotypes was found significantly different between groups (X(2) = 18.604; df = 2; P = 0.000). The frequencies for each of the AT1-R genotypes were found as 53.6% for AA (30), 42.9% for AC (24), 3.6% for CC (2) in the COPD group; 55.2% for AA (16), 41.4% for AC (12) and 3.4% for CC (1) in the control group. The distribution of AT1-R genotypes did not change significantly between groups. Allele frequencies of interested genes were not significantly different between groups. We suggest that AGT polymorphism may play a role for the development of COPD. We believe these data can be served for large scale population genetics research, considering the frequency of AGT and AT1-R genes and alleles in COPD patients in the Turkish population.

Visfatin and ghrelin: can they be forthcoming biomarkers or new drug targets for asthma?

BACKGROUND & AIM: Asthma represents chronic inflammation of the airways and is associated with bronchial hyperresponsiveness and reversible airway obstruction. A novel adipokine visfatin and an appetite-modulating hormone ghrelin play a role in several diseases related with inflammation. Although visfatin is a pro-inflammatory adipokine, ghrelin mainly exerts anti-inflammatory effects. However, very little is known about the role of visfatin and ghrelin in asthma. In the present study, we aimed to investigate the role of visfatin and ghrelin in asthma by evaluating their serum levels in asthmatic patients. MATERIALS AND METHODS: This study was performed on 27 asthma and 23 healthy controls. Blood samples were collected in tubes without EDTA. Serum levels of visfatin and ghrelin were measured by human ELISA assay kits. Statistical analyses were performed by SPSS 16.0 package program and differences were considered statistically significant at p < 0.05. RESULTS: Serum levels of visfatin and ghrelin were significantly higher in asthma group (respectively; p = 0.001, p = 0.002). CONCLUSION: While visfatin has a pro-inflammatory role, ghrelin exerts an anti-inflammatory effect in asthma. Therefore, visfatin can be a forthcoming biomarker and ghrelin may be a new anti-inflammatory drug target to diagnose and treat asthmatic patients.

Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats.

Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R) injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group). Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (p<0.01), levels of MDA, NO, and inducible nitric oxide synthase (iNOS) positive cells (p<0.01, p<0.05, respectively), and increased SOD, GPx, and CAT activities (p<0.001, p<0.01, p<0.05, respectively) compared with the I/R group that did not receive ebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (p<0.01, p<0.05, p<0.001) and MDA and NO levels (p<0.05, p<0.01) and decreased SOD, GPx, and CAT activities (p<0.05) compared with the sham group. The results of this study suggest that ebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

Nephrotoxic effects of varenicline as the most effective drug used for smoking cessation: a preliminary experimental study.

PURPOSE: Varenicline is a new most effective drug for smoking cessation. Its effect on kidney functions remains unclear. This study purposed to investigate whether varenicline causes nephrotoxicity in rats. METHODS: Fifteen rats were randomly assigned to three groups: control, 0.0125 mg kg(-1) varenicline and 0.025 mg kg(-1) varenicline (single dose for 3 days, i.p.). Before and after experimental period, serum neutrophil gelatinase-associated lipocalin, creatinine and urea levels were measured. Total oxidant and antioxidant status were measured in kidney homogenates. Histological examination was performed in kidney. RESULTS: The nephrotoxic effects of varenicline were detected by histopathological and biochemical examinations in the varenicline treatment groups. No change was observed in the control group. CONCLUSIONS: These findings firstly indicate that a 3-day varenicline treatment causes nephrotoxic effects in rats.