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Herpes simplex virus 1 is consistently the most common cause of sporadic encephalitis worldwide which leaves neurological deficits in more than 60% of survived patients.

BACKGROUND/AIMS The aim of this study was to investigate the effects of Nigella sativa (NS) oil form on reducing the damage caused by indomethacin in the stomach and duodenum of rats owing to their antioxidant and anti-inflammatory properties. MATERIAL and METHODS The rats were divided into 4 groups: group 1, saline-treated control group; group 2, NS-treated control group; group 3, saline-treated ulcer group and ulcers caused by indomethacin (30 mg/kg) and administration of physiological serum; group 4, NS-treated ulcer group, which is the group receiving NS oil after administration of indomethacin. At the end of the study, blood samples collected from animals were examined for tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and glutathione (GSH), malondialdehyde (MDA) levels and myeloperoxidase (MPO),and Na+/K+-ATPase activities in gastric and intestinal tissue samples. RESULTS Levels of TNF-alpha and IL-1 beta in serum and MDA and MPO values in tissue were found to be higher in the saline-treated ulcer group than in the saline-treated control group. In addition, tissue GSH and Na+/K+-ATPase levels were found to be lower. These values were found to be reversed when comparing NS-treated ulcer group to saline-treated ulcer group. Histopathological findings showed epithelial regeneration and improvement instead of dense tissue damage. CONCLUSION The strong antioxidant and anti-inflammatory effects of NS against potential small intestine and gastric damage were shown using an experimental indomethacin-induced ulcer model in rats. Hence, our study suggests that NS used together with indomethacin can prevent gastrointestinal damage; thus, this agent can create a new clinical therapeutic principle.

Cholestasis is associated with the accumulation of bile acids and bilirubin in the hepatocytes and leads to liver injury. Pregnane X Receptor (PXR) coordinates protective hepatic responses to toxic stimuli, and this receptor was reported to stimulate bile secretion by increasing MRP2 expression. Since PXR activators were reported to be anti-inflammatory in the liver, PXR was proposed as a drug target for the treatment of chronic inflammatory liver diseases. We investigated the potential protective effect of spironolactone (SPL), an enzyme inducer, in hepatotoxicity induced by bile duct ligation in rats. Wistar Albino (250-300 g) rats were divided into the control group and the bile duct ligated (BDL) group. BDL group was divided into three subgroups; following BDL, for 3 days, the first group received propylene glycol (vehicle of SPL) (blinded), the second subgroup received spironolactone (SPL) (200 mg/kg oral), and the third subgroup received SPL for 3 days, starting 3 days after the bile duct ligation, in order to investigate if it has a healing effect after hepatitis had developed. The control group was sham-operated and received saline. At the end of the experiment, blood and tissue samples were collected. Serum TNF-α, NF-ĸB, bilirubin, IL-6 levels, ALT, AST, ALP activities and tissue MPO activity and oxidant damage increased after the bile duct ligation was significantly decreased following SPL administration. PXR and MRP2 activity showed an increase in the hepatocytes as a result of the treatment. In conclusion, it was observed that SPL administration significantly decreases liver inflammation and damage related to BDL.

Objectives: The purpose of this study was to investigate possible protective effects of St. John's wort in the hepatic ischemia/reperfusion injury. Material and Methods: The hepatic artery, portal vein, and bile duct were all clamped for 45 minutes to induce ischemia in rats, and after that reperfusion for 1 hour. SJW was administrated orally, once a day for 3 days before ischemia/reperfusion. The aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and interleukin levels were measured in the serum samples. Luminol chemiluminescence, lucigenin luminol chemiluminescence levels; myeloperoxidase. The sodium-potassium ATPase (Na+/K+ ATPase) activity was determined in the liver tissue, and caspase-3 and caspase-9 activity with the bcl-2/bax ratio were measured by the western blot analysis. Results: The St. John's wort administration recovered the aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and IL-1 beta levels serum parameters meaningfully, while ischemia/reperfusion caused an increase in luminol chemiluminescence, lucigenin luminol chemiluminescence, myeloperoxidase, caspase-3, and caspase-9 activity and led to a decrease in the B-cell lymphoma-2/bcl-2-associated X protein (bcl-2/bax) ratio and the Na+/K+ ATPase activity. Conclusion: The obtained results indicate protective effects of St. John's wort on the ischemia/reperfusion injury through various mechanisms, and we are able to suggest that St. John's wort can clinically create a new therapeutic principle.

Sağlık Meslek Liselerinden (SML) mezun olan öğrencilere sınavsızgeçiş hakkı tanınması ile 2006-2009 yılları arasında, M.Ü Sağlıkhizmetleri Meslek Yüksekokulu, Tıbbi Laboratuvar Teknikleri(TLT) programına kayıt yaptıran öğrencilerin çoğunluğunuHemşirelik bölümü mezunları oluşturmuştur. Tıbbi LaboratuvarBölümü (TBL) dışındaki bölümlerden gelen öğrencilerde, meslekieğitim alt yapısının ciddi bir fark yaratmayacağı düşünülse deönemli sorunlarla karşılaşılmıştır.Sorunların en başında, kamu hastanelerine hemşire olarakatanmış, yoğun tempoda çalışan öğrencilerimizin durumugelmiştir. Özellikle tıbbi laboratuvar teknikerinin temel becerileriiçin belirgin yetersizlikleri olan hemşirelik çıkışlı öğrencilerimizin,eksiklerini tamamlama gayretleri olsa da, bunun için enerjileri vezamanları kalmamıştır.Çalışmamızda, TLT programına kayıt yaptıran Hemşirelikbölümü öğrencileri ile ilgili görünür sorunları irdelemek vegöremediklerimizi ortaya çıkarmak amacıyla anket çalışmasıyapılmıştır. Diğer bir amacımız da öğrencilerimizin “karasızlıkanalizlerini” yaparak, mesleki kariyerleri için kendilerine faydalıbir yönlendirmede bulunabilmektir.2007–2009 eğitim öğretim yıllarında TLT programımızakayıtlı, 71’i SML Hemşirelik bölümü mezunu, toplam 87öğrenciye uygulanan anket sonucunda, öğrencilerin %40,2’sininhemşire olarak çalıştığı ve % 57,5’nin KPSS sınavı ile “Hemşire”olarak atanmak istediği belirlenmiştir. Ortaya çıkan çelişkilidurum ise öğrencilerin üniversite mezuniyetleri sonrasında, “TıbbiLaboratuvar Teknikeri” olarak çalışmayı tercih edeceklerinibildirmeleri (%82,8) ve meslek tanımı olarak “Tıbbi LaboratuvarTeknikerliğini “seçmeleri (%59,8) olmuştur.Sonuç olarak, Hemşirelik Bölümünden mezun öğrencilerin,bilinçli olmayan bir tercihle TLT programına devam ettikleri;mesleki tercihlerindeki karasızlığın sürdüğü belirlenmiştir., The majority of the students enrolled in the M.U Vocational Schoolof Health Related Professions, Medical Laboratory Techniques(MLT) program were graduated from Nursing Departmentbetween the years 2006-2009 with the granting of the right ofpassing without examination to the students graduated from HealthVocational High Schools (HVS). Although the vocational educationinfrastructure of students from departments outside the MedicalLaboratory Department (MLD) is not seen as a serious problem,it has encountered significant problems. At the beginning of theproblems, assigned as a nurse in public hospitals it has becomebusy schedule working conditions of our students. Especially theyhave apparent lack of basic skills for laboratory training, but havenot enough time to develop their lacking skills.In our study, a questionnaire study was conducted in order toinvestigate visible problems related to the students of the NursingDepartment enrolled in the MLT program and to reveal what wecannot see. Our another aim, making a useful guidance for theirprofessional carrier and choices. In the academic year 2007-2009,according results of our survey, that it applied to 87 students (71nurse) from MLP, 40, 2% of students worked as nurse, 57, 5%want to be assigned by KPSS exam as nurse. And we determineda dilemma, which the nursing graduate students, they wouldprefer to work as medical laboratory technician (82, 8%) and aftertheir graduation will define themselves as “Medical LaboratoryTechnician” (59.8%).In conclusion, the students who graduated from the NursingDepartment continue their TLT program with an unintentionalpreference; It has been determined that unfairness in professionalpreferences continues.

The protective effects of ACE inhibitor, Captopril, and angiotensin receptor blocker, Valsartan, were evaluated in the treatment of chronic renal failure (CRF) with and without the presence of N-acetylcysteine (NAC). The renal mass of Wistar albino rats was reduced at a rate of 5/6. Captopril, Valsartan and NAC were applied intra-peritoneal alone or in combination. Blood pressure and heart rate were monitored at weekly intervals over a period of six weeks. Serum creatinine, blood urea nitrogen (BUN), lactate dehydrogenase (LDH) activity, cytokines (TNF-alpha, IL-1 beta, IL-6) concentrations, urinary volume, creatinine, and both serum and urinary electrolyte levels were measured. In addition, the apoptosis rate of white blood cells was analysed from plasma samples. Tissue samples from the brain, heart, aorta and kidneys were used for analysis of the collagen content besides tissue luminol, lucigenin, malondialdehyde (MDA) and glutathione (GSH) levels. A significant difference was determined between the CRF group and the control group with regard to heart rate, blood pressure, serum creatinine, BUN, LDH, cytokines and urinary electrolyte levels. Furthermore, monocyte and neutrophil apoptosis, tissue luminol, lucigenin, malondialdehyde and collagen levels were found to increase. Tissue glutathione levels were found to decrease indicating oxidative damage. These results indicate that oxidative mechanisms induce tissue damage in CRF, and the angiotensin receptor blocker, Valsartan, improved oxidative tissue damage when used in combination with the ACE inhibitor, Captopril or NAC, yielded better results and could be a novel approach for the treatment of CRF when used in combination with anti-oxidants.

BACKGROUND & AIM Alpha lipoic acid (LA) was shown to exert neuroprotection in trauma-induced spinal cord injury (SCI), which is frequently associated with urinary bladder complaints in patients with SCI. Accordingly, the protective effects of LA on biochemical and histological changes in bladder as well as functional studies were assessed. METHODS Wistar albino rats were divided as control, SCI, and LA (50 mg/kg/day, ip) treated SCI groups (SCI+LA). The standard weight-drop (100 g/cm force at T10) method was used to induce a moderately severe SCI. One week after the injury, neurological examination was performed and the rats were decapitated. Bladder samples were taken for histological examination, functional (isolated tissue bath) studies, and for the measurement of biochemical parameters (malondialdehyde, MDA; gluthathione, GSH; nerve growth factor, NGF; caspase-3, luminol and lucigenin chemiluminescences). RESULTS SCI caused a significant (P

Aim: Reactive oxygen species play an important role in the pathophysiology of intestinal ischemia/reperfusion (I/R) injury by causing apoptosis. The present study aimed at exploring the possible protective effect of Saint John’s Wort (SJW) extract in I/R injury.Materials and Methods: Twenty four healthy male Wistar rats of 6 to 8 weeks old weighting averagely 200 to 250 g were studied. They were fed on standard rat food and drinking water at room temperature with 12/12 hours periods of day and night. SJW (300 mg/kg, peroral) or saline was given by oral route for 3 days prior to ischemia, 30 minutes before the ischemia, and just before reperfusion. To the rats in the control group, sham operation and application of saline were done. Levels of TNF-α, IL-1β and LDH were measured in the serum samples. In the small bowel tissue, levels of malonaldehyde (MDA) and glutathione (GSH) and activity of myeloperoxidase (MPO) and Na-K ATPase and level of caspase-3/β-actine and Bcl-2/β-actine were measured.Results: I/R increased serum levels of LDH, TNF-α and IL-1β, small bowel level of MDA and MPO whereas it decreased level of GSH and activity of Na-K ATPase in the small bowel tissue. The level of caspase-3/β-actine increased while the level of Bcl-2/β-actine decreased in the I/R group compared to the controls. With the application of SJW, these values approached the control levels.Conclusion: These results indicate that SJW recovers small bowel function by reducing oxidation injury during I/R.

Objective: In the present study, it was aimed to study the antioxidant effects of spironolactone (SPL) to determine its possible protective effects in hepatic ischemia reperfusion injury. Material and Methods: Hepatic artery, portal vein, and bile duct of Wistar albino rats were clamped for 45 minutes under anesthesia to form an ischemia period. Then reperfusion was allowed and the rats were decapitated 60 minutes later. SPL (20 mg/kg, p.o.) or SF was orally administered for 30 minutes before ischemia. Rats in the control arm underwent sham surgery and were administered isotonic saline. Liver function was studied by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1beta (IL-1 beta) levels. Malondialdehyde (MDA), glutathione (GSH), luminol, and lucigenin levels, myeloperoxidase (MPO) and Na+-K+- ATPase enzyme activities were analyzed to study tissue injury under light microscope. Results: While IR increased AST, ALT, TNF-alpha, and IL-1 beta levels and MDA, luminol, and lusigenin levels and MPO activities, it caused a decrease in GSH levels and Na+K+-ATPase activity. Spironolactone administration significantly improved these values. Conclusion: Protective effects of SPL against ischemia/reperfusion injury via various mechanisms suggest that this agent may become a novel treatment agent in clinical practice.

The aim of this study was to evaluate the possible protective effect of spironolactone (SPL) and role of the Na-K ATPase pump on intestinal ischemia/reperfusion injury. In our study, the period of ischemia was established by clamping the mesenteric artery for 45 minunder anesthesia in Wistar albino rats and the animals left for reperfusion at the end of this period were decapitated after one hour. Spironolactone (20 mg kg(-1)) was administered orally for three days before ischemia, 30 minbefore ischemia. The control group rats were subjected to the Sham operation and administered saline solution. TNF-alpha and IL-1 beta levels were measured in the serum samples. Ileal Na+/K+-ATPase, myeloperoxidase (MPO) analysis were performed. Structural injury was assessed histopathologically. Ischemia/reperfusion increased serum TNF-alpha and IL-1 beta levels together with MPO activity, whereas these values were maintained at the control group levels through SPL activation. However, ischemia/reperfusion decreased Na+/K+-ATPase activity in ileal tissues; however, these parameters were found to be significantly increased with SPL activation. The protective effect of SPL against ischemia/reperfusion injury by different mechanisms, mainly the activity of the Na+/K+-ATPase pump, suggests that this nontoxic agent may constitute a new clinical therapeutic principle.

OBJECTIVE: Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide. METHODS: The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49 +/- 10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46 +/- 14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples. RESULTS: Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p

The "cholinergic anti-inflammatory pathway" provides neurological modulation of cytokine synthesis to limit the magnitude of the immune response. This study aimed to evaluate the impact of the cholinergic anti-inflammatory pathway on the extent of tissue integrity, oxidant-antioxidant status and neutrophil infiltration to the inflamed organ in a rat model of acetic acid-induced colitis. Colitis was induced by intrarectal administration of 5% acetic acid (1ml) to Sprague-Dawley rats (200-250g; n=7-8 per group). Control group received an equal volume of saline intrarectally. The rats were treated with either nicotine (1mg/kg/day) or huperzine A (0.1mg/kg/day) intraperitoneally for 3 days. After decapitation, the distal colon was scored macroscopically and microscopically. Tissue samples were used for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Formation of reactive oxygen species was monitored by using chemiluminescence (CL). Nuclear factor (NF)-κB expression was evaluated in colonic samples via immunohistochemical analysis. Trunk blood was collected for the assessment of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-10, resistin and visfatin levels. Both nicotine and huperzine A reduced the extent of colonic lesions, increased colonic MDA level, high MPO activity and NF-κB expression in the colitis group. Elevation of serum IL-1β level due to colitis was also attenuated by both treatments. Additionally, huperzine A was effective to reverse colitis-induced high lucigenin-enhanced CL values and serum TNF-α levels. Colitis group revealed decreased serum visfatin levels compared to control group which was completely reversed by nicotine. In conclusion, modulation of the cholinergic system either by nicotine or ACh esterase inhibition improved acetic acid-induced colonic inflammation as confirmed by macroscopic and microscopic examination and biochemical assays.

Objective: Obstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular morbidity and mortality. We aimed to investigate the matrix metalloproteinase-9 (MMP-9) level and MMP-9 gene polymorphism in sleep apnea patients with or without cardiovascular disease. Study Design: Case-control study. Material and Methods: Two hundred nine patients [Mean age (±SD), 47 (±12) yrs; M/F, 170/39] diagnosed with sleep-disordered breathing were included in the study. Serum MMP-9 level was performed using enzyme-linked immunosorbant assay (ELISA) and MMP-9 gene polymorphism with polymerase chain reaction-restriction fragment length polymorphism. We divided the patient group into two subgroups: (1) patients with confirmed cardiovascular disease, i.e. CV-P Group and (2) patients without cardiovascular disease, CV-N Group. We compared all parameters between the two groups. Results: There were 56 OSAS patients with cardiovascular disorder (CV-positive group) and 153 OSAS patients without cardiovascular disorder (CVnegative group). CC, CT and TT genotype distributions between groups were similar [31 (55%), 25 (45%), 0 (0%) vs 88 (57%), 61 (40%), 4 (3%); respectively, p>0.05]. MMP-9 level was significantly higher in CV-P patients (442.7±139.3 pg/mL) than in CV-N patients (364.4±165.0 pg/mL; p=0.0018). Conclusion: Our results showed that the presence of MMP-9 polymorphism was not associated with cardiovascular disease. MMP-9 level was higher in OSAS patients with cardiovascular disorders than without cardiovascular disorders. Finally, MMP-9 genotype was not associated with serum MMP-9 levels. Turkish Başlık: Kardiyovasküler Hastalığı olan ve olmayan Obstrüktif Uyku Apne Sendromlu Hastalarda Matriks Metalloproteinaz-9 Aktivitesi ile Gen Polimorfizmi Anahtar Kelimeler: Kardiyovasküler hastalıkları, MMP-9, polimorfizm, uyku apnesi, hipertansiyon Amaç: Obstrüktif uyku apne sendromu (OUAS) artmış kardiyovasküler morbidite ve mortalite ile ilişkilidir. Bu çalışmada kardiyovasküler hastalığı olan ve olmayan uyku apneli hastalarda matriks metalloproteinaz-9 (MMP-9) düzeyi ile MMP-9 gen polimorfizminin araştırılması amaçlandı. Gereç ve Yöntemler: Uykuda solunum bozukluğu teşhisi almış 209 hasta [Ortalama yaş (±SS), 47 (±12) yıl; E/K, 170/39] çalışmaya dahil edildi. Serum MMP-9 düzeyi ELISA, MMP-9 gen polimorfizmi polimeraz zincir reaksiyonu ve restriksiyon fragmanı uzunluk polimorfizmi ile DNA örneklerinde belirlendi. Hastalar kardiyovasküler hastalığı olan, KV-P grubu ve kardiyovasküler hastalığı olmayan, KV-N grubu olmak üzere iki alt gruba ayrıldı. Bulgular: Kardiyovasküler hastalığı olan (KV-P grup) 56 ve kardiyovasküler hastalığı olmayan (KV-N grup) 153 OUAS hasta tesbit edildi. Gruplar arası CC, CT ve TT genotip dağılımı benzer [31 (55%), 25 (45%), 0 (0%) vs 88 (57%), 61 (40%), 4 (3%); sırasıyla, p>0.05] tesbit edildi. MMP-9 düzeyi KV-P hastalarda (442.7±139.3 pg/mL) KV-N hastalara (364.4±165.0 pg/mL) göre anlamlı (p=0.0018) yüksek saptandı. Sonuç: Bulgularımız, MMP-9 polimorfizm varlığının kardiyovasküler hastalıklarla ilişkili olmadığını gösterdi. MMP-9 düzeyi kardiyovasküler hastalığı olan OUAS'lı hastalarda kardiyovasküler hastalığı olmayanlara göre yüksek saptandı. Sonuç olarak, MMP-9 genotipi serum MMP-9 düzeyi ile ilişkili bulunmadı.

Objective: The goal of the present study was to investigate the effects of 5-lipoxygenase (5-LOX) inhibition, alone and with cyclooxygenase (COX) inhibitors, on inflammatory parameters and apoptosis in ischemia/reperfusion (I/R)-induced myocardial damage in rats. For this purpose, zileuton, a selective and potent inhibitor of 5-LOX, resulting in suppression leukotriene production, was used. Methods: Male Wistar rats (200-250 g; n=12 per group) were used in the study. I/R was performed by occluding the left coronary artery for 30 minutes and 2 hours of reperfusion of the heart. Experimental groups were I/R group, sham I/R group, zileuton (5 mg/kg orally, twice daily)+I/R group, zileuton+indomethacin (5 mg/kg intraperitoneally)+I/R group, zileuton+ketorolac (10 mg/kg subcutaneously)+I/R group, and zileuton+nimesulide (5 mg/kg subcutaneously)+I/R group. Following I/R, blood samples were collected to measure tumor necrosis factor alpha (TNF-α), and left ventricles were excised for evaluation of microscopic damage; malondialdehyde (MDA), glutathione, nuclear factor (NF)-κB assays; and evaluation of apoptosis. Results: Left ventricle MDA in I/R group was higher compared to sham group; however, it did not show significant change with zileuton. Although tissue injury in I/R group was less severe in all treatment groups, it was not statistically significant. NF-κB H-score and apoptotic index, which were higher in I/R group compared to sham I/R, were decreased with application of zileuton (H-score: p

Background There are contradictory results about stress response in hypothyroidism and in exercising with variant intensities. We aimed to investigate the potential anxiolytic and protective effects of different intensities of exercise on acute psychological stress in hypothyroidism. Methods Rats (N.=48) were divided as sedentary, moderate intensity (MIE) and high intensity exercise (HIE) groups. Rats were administered intraperitoneally with 6-n-propyl-2-thiouracil (PTU, 10 mg/kg) for 15 days to induce hypothyroidism. Starting by the 3rd week, treadmill exercise was performed moderately (30 min/day) or at high intensity (60 min/day) for 6 weeks, 5 days/week. At the end of the 8th week, exposure to water avoidance stress was used for induction of acute stress. Anxiety-like behavior was determined by holeboard test before and after stress inductions. Serum IL-1β and IL-6 assays, and myeloperoxidase activity (MPO), malondialdehyde (MDA), and glutathione (GSH) measurements, and histological analysis of heart, liver, stomach and small intestine were made. Results All groups showed increased anxiety-like behavior following acute stress induction. After acute stress induction, increased MPO and MDA levels in heart and elevated MPO activity in liver were inhibited in PTU-treated HIE group. In MIE rats, increased MPO and declined GSH levels of the gastric tissue and small intestine, and elevated MDA levels of gastric tissue were reversed in PTU-treated MIE group. Major histological changes that occurred by both intensities of exercise under stress condition were improved by PTU. Conclusions Our results indicate that hypothyroid state may be protective against stress- and exhaustive exercise-induced oxidative damage.

Adipokines are markers of insulin resistance and play a role in the atherosclerotic process. The association of adipokines with the macrovascular complications of type 1 diabetes mellitus (DM) needs to be determined. The aim of this study was to measure serum adiponectin, leptin, and resistin levels in type 1 DM patients and investigate their relationship with carotid intima media thickness (CIMT), a clinical marker of atherosclerosis.Seventy-five type 1 DM patients and 115 sex and age-matched healthy controls were included in the study. Serum adiponectin, leptin, and resistin levels were measured by the enzyme-linked immunosorbent assay (ELISA method). CIMT was assessed by Doppler ultrasonography.Adiponectin levels in diabetics were higher (25.8±14.8 μg/mL vs. 5.5±7.3 μg/mL; P0.0001) and leptin levels were lower than controls (9.4±6.2 ng/mL vs. 12.8±8.6 ng/mL; P=0.01). Resistin levels were also higher in the diabetic group compared to controls (2.1±1.4 ng/mL vs. 1.6±0.8 ng/mL; P=0.04). Adiponectin was correlated negatively with CIMT (r=-0.24, P=0.03), age (r=-0.30, P=0.02), BMI (r=-0.33, P=0.02), waist-to-hip ratio (WHR) (r=-0.38, P=0.01) and positively with creatinine (r=0.44, P=0.004). Leptin levels were correlated with total cholesterol (r=0.53, P=0.01) and high-density lipoprotein (HDL) (r=0.67, P=0.001). Resistin was correlated with CIMT (r=0.24, P=0.03) and systolic blood pressure (r=0.48, P=0.009). Multivariate analysis revealed resistin and creatinine to be independent predictors of CIMT among adiponectin, leptin, resistin, WHR, glycosylated hemoglobin (HbA1c), and creatinine.Increased adiponectin correlates negatively and resistin positively with CIMT in type 1 diabetic patients, but adjusting for other known predictors reveals only resistin to be associated with subclinical atherosclerosis in this group of patients.

Aims: To investigate the effect of sildenafil citrate (SIL) on the extent of tissue integrity, oxidant-antioxidant status and apoptosis in rats with colitis. Main methods: Colitis was induced by trinitrobenzenesulphonic acid (TNBS) in 40% ethanol (30 mg/ml; 0.8 ml) given intrarectally to Sprague-Dawley rats. Sildenafil (25 mg/kg/day) was administered after the induction of colitis and the treatment was continued for 7 days. Other groups received subcutaneously either N(G)-nitro- L-arginine methyl ester (l-NAME; 25 mg/kg) or N(G)-nitro-d-arginine methyl ester (d-NAME; 25 mg/kg) before SIL. After decapitation, the distal colon was scored and stored for the measurement of malondialdehyde (MDA) level, glutathione (GSH) content, myeloperoxidase (MPO) activity and apoptosis. Oxidant generation was monitored by using chemiluminescence (CL). Blood was collected for tumor necrosis factor (TNF)-? and interleukin (IL)-10 assays. Key findings: The macroscopic lesion score of the colitis group was reduced by SIL (p < 0.01) and this effect was abolished by l-NAME (p < 0.01). Increase in colonic MDA along with a concomitant decrease in GSH of the colitis group was reversed by SIL (p < 0.01 and p < 0.001, respectively). l-NAME prevented the effect of SIL on GSH content (p < 0.001). Sildenafil also reduced the elevated MPO of the colitis group (p < 0.001) and this effect was reversed by L-NAME (p < 0.01). Increase in lucigenin CL and serum TNF-? levels in the colitis group were also prevented by SIL (p < 0.001 and p < 0.01, respectively). Significance: Sildenafil is beneficial in TNBS-induced rat colitis partially by nitric oxide-dependent mechanisms via the maintenance of oxidant-antioxidant status, prevention of apoptosis, superoxide production and cytokine release. © 2011 Elsevier Inc. All rights reserved. Marmara Üniversitesi: SAG-A-060510-0113 The authors are grateful to Marmara University Scientific Research Project Commission for the financial support of this study (Project No: SAG-A-060510-0113 ).

Background: The aim of this study was to assess the possible protective effect of proanthocyanidin against cerulein-induced acute pancreatic inflammation (AP) and oxidative injury. Methods: Sprague-Dawley rats were pretreated with proanthocyanidine (100 mg/kg, orally) or saline 15 min before cerulein was given by 20 ? g/kg subcutaneous ly at 1-h intervals within 4 hours. Six hours after cerulein or saline injections, the animals were killed by decapitation. Blood samples were collected to analyze amylase, lipase, and proinflammatory cytokines (TNF-? and IL-1b). Pancreas tissues were taken for the determination of tissue glutathione (GSH) and malondialdehyde (MDA) levels, Na + , K + -ATPase and myeloperoxidase (MPO) activities. Formation of reactive oxygen species in pancreatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes, while the extent of tissue injury was analyzed microscopically. Results: Acute pancreatitis caused a significant decrease in tissue GSH level and Na + , K + -ATPase activity, which was accompanied with significant increases in the pancreatic MDA, luminol and lucigenin chemiluminescences (CL) levels and MPO activity. Similarly TNF-? and IL-1? levels were elevated in the pancreatic group as compared to control group. On the other hand, proanthocyanidin treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by cerulein. Conclusions: Proanthocyanidine can ameliorate pancreatic injury induced by cerulein in rats, this result suggests that proanthocyanidin may have utility in treating acute pancreatititis. doi:10.4021/gr2009.02.1276

Traumatic brain injury (TBI) was induced by a weight-drop device using 300 g-1 m weight-height impact. The study groups were: control, alpha-lipoic acid (LA) (100 mg/kg, po), TBI, and TBI + LA (100 mg/kg, po). Forty-eight hours after the injury, neurological scores were measured and brain samples were taken for histological examination or determination of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels, myeloperoxidase (MPO) and Na(+)-K(+) ATPase activities, whereas cytokines (TNF-alpha, IL-1beta) were determined in blood. Brain oedema was evaluated by wet-dry weight method and blood-brain barrier (BBB) permeability was evaluated by Evans Blue (EB) extravasation. As a result, neurological scores mildly increased in trauma groups. Moreover, TBI caused a significant decrease in brain GSH and Na(+)-K(+) ATPase activity, which was accompanied with significant increases in TBARS level, MPO activity and plasma proinflammatory cytokines. LA treatment reversed all these biochemical indices as well as histopathological alterations. TBI also caused a significant increase in brain water content and EB extravasation which were partially reversed by LA treatment. These findings suggest that LA exerts neuroprotection by preserving BBB permeability and by reducing brain oedema probably by its anti-inflammatory and antioxidant properties in the TBI model.

The possible protective effects of resveratrol (RVT) against cardiotoxicity were investigated in Wistar albino rats treated with saline, saline+doxorubicin (DOX; 20 mg/kg) or RVT (10 mg/kg)+DOX. Blood pressure and heart rate were recorded on the 1st week and on the 7th week, while cardiomyopathy was assessed using transthoracic echocardiography before the rats were decapitated. DOX-induced cardiotoxicity resulted in decreased blood pressure and heart rate, but lactate dehydrogenase, creatine phosphokinase, total cholesterol, triglyceride, aspartate aminotransferase and 8-OHdG levels were increased in plasma. Moreover, DOX caused a significant decrease in plasma total antioxidant capacity along with a reduction in cardiac superoxide dismutase, catalase and Na+,K+-ATPase activities and glutathione contents, while malondialdehyde, myelopreoxidase activity and the generation of reactive oxygen species were increased in the cardiac tissue. On the other hand, RVT markedly ameliorated the severity of cardiac dysfunction, while all oxidant responses were prevented; implicating that RVT may be of therapeutic use in preventing oxidative stress due to DOX toxicity.

Amaç: Süt serumu proteinlerinin antioksidan etkileri vardır. Bu çalışmada, süt serumu proteinlerinin etanolle oluşturulan oksidatif mide ve karaciğer hasarındaki koruyucu etkileri değerlendirildi. Yöntem: Mide dokusunda reaktif oksijen türlerinin oluşumu kemilüminesans yöntemiyle takip edildi. Karaciğer ve mide dokuları histopatolojik olarak değerlendirilirken, lipit peroksidasyonu göstergesi olarak malondialdehit düzeyleri ve nötrofil infiltrasyonu için miyeloperoksidaz aktivitesi ölçüldü. Bulgular: Süt serumu proteinleriyle ön beslenmenin etanolle oluşturulan mide ve karaciğer hasarında nötrofil infiltrasyonunu ve sitotoksik serbest radikal oluşumunu önleyerek koruyucu etki yaptığı gözlendi. Sonuç: Peyniraltı suyu kaynaklı bir ürün ile beslenmenin gastrik lezyonların tedavisinda yararlı bir seçenek oluşturabileceği düşünülmektedir.

Regarding the mechanisms of renal scarring in pyelonephritis, several hypotheses have been put forward, among which oxidative stress is prominent. The present study investigated the possible protective effect of melatonin treatment against Escherichia coli-induced oxidative injury and scarring in renal tissue. For this purpose, 0.1 mL E. coli (ATCC 25922; 10(10) colony-forming units/mL) or saline was injected directly into the renal parenchyma of Wistar rats. Pyelonephritic rats were treated with either saline or melatonin (10 mg/kg) intraperitoneally. Twenty-four hours or 1 wk after E. Coli injection, rats were decapitated and trunk blood samples were collected for BUN, creatinine, tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) determination. In kidney samples, histological analysis was performed, and malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents were measured. Formation of reactive oxygen species was monitored using a chemiluminescence (CL) technique. Escherichia Coli inoculation caused a significant reduction in renal GSH levels, which was accompanied by significant increases in MDA levels, MPO activity, CL levels and collagen content of the renal tissues (P < 0.05-0.001). Similarly, serum TNF-alpha and, LDH, BUN and creatinine levels were elevated in the pyelonephritic rats when compared with control animals. Melatonin treatment reversed all these biochemical indices, as well as histopathological alterations induced by acute pyelonephritis. The protective effects of melatonin can be ascribed to its ability to inhibit neutrophil infiltration, to balance the oxidant-antioxidant status, and to regulate the generation of inflammatory mediators, suggesting a future role for melatonin in the treatment of acute pyelonephritis.

There is increasing evidence to suggest that reactive oxygen metabolites (ROMs) play a role in the pathogenesis of ischemia/reperfusion injury (I/R) in the kidney. This study was designed to determine the possible protective effect of Ginkgo biloba extract (EGb) on renal ischemia/reperfusion (I/R) injury. Wistar albino rats were unilaterally nephrectomized, and 15 days later they were subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Ginkgo biloba extract (EGb) (50 mg kg(-1) day(-1)) or saline was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the treatment period, all rats were decapitated. Kidney samples were taken for histological examination or determination of the renal malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence (CL) assay. Creatinine and urea concentrations in blood were measured for the evaluation of renal function. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were also assayed in serum samples. Ischemia/reperfusion caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of kidney tissues. Similarly, serum BUN and creatinine levels, as well as LDH and TNF-alpha, were elevated in the I/R group as compared to control group. On the other hand, EGb treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by I/R. The findings imply that ROMs play a causal role in I/R-induced renal injury and EGb exerts renoprotective effects probably by the radical scavenging and antioxidant activities.

WOS: 000353700300003, PubMed: 25923257, PURPOSE: To determine the antioxidant and anti-inflammatory effects of alfa lipoic acid (ALA) on the liver injury induced by methotrexate (MTX) in rats. METHODS: Thirty two rats were randomly assigned into four equal groups; control, ALA, MTX and MTX with ALA groups. Liver injury was performed with a single dose of MTX (20 mg/kg) to groups 3 and 4. The ALA was administered intraperitonealy for five days in groups 2 and 4. The other rats received saline injection. At the sixth day the rats decapitated, blood and liver tissue samples were removed for TNF-alpha, IL-1 beta, malondialdehyde, glutathione, myeloperoxidase and sodium potassium-adenosine triphosphatase levels measurement and histological examination. RESULTS: MTX administration caused a significant decrease in tissue GSH, and tissue Na+, K+ ATPase activity and which was accompanied with significant increases in tissue MDA and MPO activity. Moreover the pro-inflammatory cytokines (TNF-alpha, IL-beta) were significantly increased in the MTX group. On the other hand, ALA treatment reversed all these biochemical indices as well as histopathological alterations induced by MTX. CONCLUSION: Alfa lipoic acid ameliorates methotrexate induced oxidative damage of liver in rats with its anti-inflammatory and antioxidant effects.

Traumatic injury to the central nervous system results in the delayed dysfunction and neuronal death. Impaired mitochondrial function, generation of reactive oxygen species (ROS), and lipid peroxidation occur soon after traumatic spinal cord injury (SCI), while the activation of compensatory molecules that neutralize ROS occurs at later time points. The aim of the current study was to investigate the putative neuroprotective effect of the COX2 inhibitor meloxicam in a rat model of SCI. In order to induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10, was used. Injured animals were given either 2 mg/kg meloxicam or saline 30 min postinjury by intraperitoneal injection. At seven days postinjury, neurological examination was performed and rats were decapitated. Spinal cord samples were taken for histological examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and DNA fragmentation. Formation of ROS in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique. SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in CL, MDA levels, MPO activity, and DNA damage. On the other hand, meloxicam treatment reversed all these biochemical parameters as well as SCI-induced histopathological alterations. Furthermore, impairment of the neurological functions due to SCI was improved by meloxicam treatment. The present study suggests that meloxicam, reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, GSH depletion, and DNA fragmentation.

To elucidate the putative neuroprotective effects of ghrelin in subarachnoid hemorrhage (SAH)-induced brain injury, Wistar albino rats (n = 54) were divided into sham-operated control, saline-treated SAH, and ghrelin-treated (10 microg/kg/d IP) SAH groups. The rats were injected with blood (0.3 mL) into the cisterna magna to induce SAH, and were sacrificed 48 h after the neurological examination scores were recorded. In plasma samples, neuron-specific enolase (NSE), S-100beta protein, TNF-alpha, and IL-1beta levels were evaluated, while forebrain tissue samples were taken for the measurement of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species levels, myeloperoxidase (MPO), Na(+)-K(+)-ATPase activity, and DNA fragmentation ratio. Brain tissue samples containing the basilar arteries were obtained for histological examination, while cerebrum and cerebellum were removed for the measurement of blood-brain barrier (BBB) permeability and brain water content. The neurological scores were impaired at 48 h after SAH induction, and SAH caused significant decreases in brain GSH content and Na(+)-K(+)-ATPase activity, and increases in chemiluminescence, MDA levels, and MPO activity. Compared with the control group, the protein levels of NSE, S-100beta, TNF-alpha, and IL-1beta in plasma were also increased, while ghrelin treatment prevented all SAH-induced alterations observed both biochemically and histopathologically. The results demonstrate that ghrelin alleviates SAH-induced oxidative brain damage, and exerts neuroprotection by maintaining a balance in oxidant-antioxidant status, by inhibiting proinflammatory mediators, and preventing the depletion of endogenous antioxidants evoked by SAH.

Background: Oxidative stress is a mediator of secondary injury to the spinal cord following trauma. Objective: To investigate the putative neuroprotective effect of a-lipoic acid (LA), a powerful antioxidant, in a rat model of spinal cord injury (SCI). Methods: Wistar albino rats were divided as control, vehicle-treated SCI, and LA-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 50 mg/kg LA or saline at 30 minutes postinjury by intraperitoneal injection. At 7 days postinjury, neurologic examination was performed, and rats were decapitated. Spinal cord samples were taken for histologic examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and DNA fragmentation. Formation of reactive oxygen species in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique. Results: SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in luminol CL and MDA levels, MPO activity, and DNA damage. Furthermore, LA treatment reversed all these biochemical parameters as well as SO-induced histopathologic alterations. Conversely, impairment of the neurologic function caused by SCI remained unchanged. Conclusion: The present study suggests that LA reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, glutathione depletion, and DNA fragmentation.

The present study was undertaken to determine whether resveratrol (RVT) could ameliorate ionizing radiation-induced oxidative injury. After a 10-days pre-treatment with RVT (10 mg/kg/day p.o.), rats were exposed to whole-body IR (800 cGy) and the RVT treatment was continued for 10 more days after the irradiation. Irradiation caused a significant decrease in glutathione level, while malondialdehyde levels, myeloperoxidase activity and collagen content were increased in the liver and ileum tissues. Similarly, plasma lactate dehydrogenase and pro-inflammatory cytokine levels, 8-hydroxy-2'-deoxyguanosine and leukocyte apoptosis were elevated, while antioxidant-capacity was reduced in the irradiated rats as compared with the control group. Furthermore, Na(+), K(+)-ATPase activity was inhibited and DNA fragmentation was increased in the ileal tissues. Resveratrol treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. In conclusion, supplementing cancer patients with adjuvant therapy of resveratrol may have some benefit for a more successful radiotherapy.

Ischemia and reperfusion (I/R) injury is characterized by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. This study was designed to assess the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (CysLT1), on hepatic I/R injury in rats. Wistar albino rats through clamping hepatic artery, portal vein, and bile duct, were subjected to 45 min of hepatic ischemia followed by 60 min reperfusion period. Montelukast (10 mg/kg; i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of the reperfusion period, the rats were killed by decapitation. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and proinflammatory cytokines (TNF-α and IL-1β) were determined in blood samples. Malondialdehyde (MDA), and glutathione (GSH) levels and myeloperoxidase (MPO) and Na + , K + -ATPase activities were determined in the liver tissue samples while formation of reactive oxygen species was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically. Serum ALT, AST, and LDH activities were elevated in the I/R group, while this increase was significantly decreased by montelukast treatment. Hepatic GSH levels and Na + , K + -ATPase activity, significantly depressed by I/R, were elevated back to control levels in montelukast-treated I/R group. Furthermore, increases in tissue luminol and lucigenin CL, MDA levels, and MPO activity due to I/R injury were reduced back to control levels with montelukast treatment. Since montelukast administration alleviated the I/R-induced liver injury and improved the hepatic structure and function, it seems likely that montelukast with its anti-inflammatory and antioxidant properties may be of potential therapeutic value in protecting the liver against oxidative injury due to ischemia-reperfusion.

Background. Sepsis is associated with enhanced generation of reactive oxygen species, which leads to multiple organ dysfunctions. Based on the potent an- tioxidant effects of silymarin, we investigated the pu- tative protective role of silymarin against sepsis- induced oxidative damage in lung and brain tissues. Materials and methods. Sepsis was induced by cecal ligation and perforation (CLP). Sham and CLP groups received either vehicle or silymarin (50 mg/kg, p.o.) or 150 mg/kg i.p. N-acetylcysteine (NAC) for 10 days prior and immediately after the operation. Six hours after the surgery, rats were decapitated and blood was col- lected for the measurement of proinflammatory cyto- kines (tumor necrosis factor-alpha, interleukin-1 (IL- 1), and IL-6) levels, lactate dehydrogenase activity, and total antioxidant capacity. Lung and brain sam- ples were taken for the measurement of malondialde- hyde and glutathione levels, myeloperoxidase activity, thromboplastic activity, and also for histological as- sessment. Formation of reactive oxygen species in tis- sue samples was monitored by using chemilumines- cence technique with luminol and lusigenin probe. Results. Sepsis increased serum TNF-, IL-1, IL-6 levels, and lactate dehydrogenase activity and de- creased total antioxidant capacity. On the other hand, tissue glutathione levels were decreased while malon- dialdehyde levels and myeloperoxidase activity were increased in both the lung and the brain tissues due to CLP. Furthermore, luminol and lucigenin chemilumi- nescence were significantly increased in the CLP group, indicating the presence of the oxidative dam- age. Silymarine and NAC treatment reversed these biochemical parameters and preserved tissue mor- phology as evidenced by histological evaluation. Conclusions. Silymarin, like NAC, reduced sepsis- induced remote organ injury, at least in part, through its ability to balance oxidant-antioxidant status, to inhibit neutrophil infiltration, and to regulate the re- lease of inflammatory mediators. © 2008 Elsevier Inc. All rights reserved.

Regarding the mechanisms of ifosfamide (IFO)-induced urinary toxicity, several hypotheses have been put forward, among which oxidative stress and depletion of glutathione are suggested. This investigation elucidates the role of free radicals in IFO-induced toxicity and the protection by resveratrol, a natural phytoalexin. Wistar albino rats were injected intraperioneally with saline (0.9% NaCl; control), saline + resveratrol (RVT; 10 mg/kg/day), ifosfamide (IFO; 50 mg/kg/day) or IFO + RVT for 5 days. Urine was collected for 24 h during the 5th day, and at the 120th h after the first injections, animals were killed by decapitation and trunk blood was collected. Lactate dehydrogenase (LDH) activity, total antioxidant capacity (AOC) and pro-inflammatory cytokines TNF-{alpha}, IL-{beta} and IL-6 were assayed in plasma samples. Kidney and bladder tissues were obtained for biochemical and histological analysis. Formation of reactive oxygen species in the tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. The results demonstrated that IFO induced a Fanconi syndrome characterized by increased urinary sodium, phosphate, glucose and protein, along with increased serum creatinine and urea levels. On the other hand, RVT markedly ameliorated the severity of renal dysfunction induced by IFO. Furthermore IFO caused a significant decrease inmore » plasma AOC, which was accompanied with significant increases in the levels of the pro-inflammatory mediators and LDH activity, while RVT treatment reversed all these biochemical indices. In the saline-treated IFO group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity and collagen content were increased in both tissues, which were in parallel with the increases in CL values. In the RVT-treated IFO group, all of these oxidant responses were prevented significantly. Our results suggest that IFO causes oxidative damage in the renal and bladder tissues and resveratrol, via its antioxidant effects, protects these tissues. Therefore, its therapeutic role in preventing the development of chemotherapeutic drug-induced major toxicity in the urinary system requires further elucidation.« less