Mustafa Kul

Enteral glutamine and/or arginine supplementation have favorable effects on oxidative stress parameters in neonatal rat intestine.

Objective: To investigate and compare the effects of enteral glutamine and arginine supply on lipid peroxidation and antioxidant enzyme levels in the small intestine of healthy breast-fed rats. Materials and Methods: The study comprised 40 newborn Sprague-Dawley rats born to 5 mother rats. Newborn rats were randomly divided into 4 groups. Starting from day 1 until day 21, group I received only breast milk; group II received breast milk and 200 mg/kg/day oral glutamine; group III received breast milk and 200 mg/kg/day oral arginine; and group IV received breast milk, 200 mg/kg/day glutamine, and 200 mg/kg/day arginine. Malondialdehyde levels and glutathione peroxidase (GPx) and superoxide dismutase activities were measured. Results: The lowest malondialdehyde levels were found in group II (P = 0.0001). Superoxide dismutase activity was found to be significantly higher in group II than group I (P < 0.001). Of the 4 groups, GPx activity was highest in group IV. GPx activity in group II was significantly higher than in group I (P = 0.001) or group III (P = 0.001). GPx activity was higher in group IV than in group I (P = 0.001) or group III (P = 0.001). Conclusions: Enteral glutamine alone or in the presence of arginine has favorable effects on oxidative stress not only in experimental models of hypoxia-reoxygenation, but also in healthy newborn rats. This suggests that in premature neonates with insufficient oxidative resistance, glutamine and arginine supplementation may help prevent necrotizing enterocolitis.

Proanthocyanidin prevents methotrexate-induced intestinal damage and oxidative stress.

Mucositis is an important dose-limiting side effect of methotrexate for which there is no definitive prophylaxis or treatment. This study was designed to investigate whether proanthocyanidin had a protective effect on methotrexate-induced small intestine damage. Twenty-eight albino rats were randomized into four groups. To the first group, methotrexate was applied as a single dose (20mg/kg) intraperitoneally. To the second group, proanthocyanidin (100mg/kg) was given orally every day by gavage in addition to methotrexate application until the rats were killed. To the third group, only proanthocyanidin was administered. The fourth group was the control. All animals were sacrificed 4 days after the intraperitoneal injection of methotrexate for histopathological examination and the assay for tissue malondialdehyde, superoxide dismutase and glutathione peroxidase levels. Methotrexate caused jejunal injury and increased malondialdehyde levels. Administration of proanthocyanidin decreased the jejunal damage and malondialdehyde level, which were caused by methotrexate treatment and increased superoxide dismutase and glutathione peroxidase levels. These results suggest that proanthocyanidin may protect the small intestine of rats from methotrexate-induced damage. The effects of proanthocyanidin could result from its antioxidant properties.

α-Lipoic Acid and Ebselen Prevent Ischemia/Reperfusion Injury in the Rat Intestine

PurposeReactive oxygen species (ROS) and reactive nitrogen species (RNS), generated during tissue reperfusion, are characteristic of ischemia/reperfusion (I/R) injury. We conducted this study to evaluate the protective effect of α-lipoic acid (α-LA) and ebselen against intestinal I/R injury.MethodsForty Sprague-Dawley rats were divided into five groups: a sham-operated group; an I/R group, subjected to intestinal ischemia for 45 min and reperfusion for 3 days; an I/R+α-LA group; an I/R+ebselen group; and an I/R+α-LA+ebselen group. We collected ileal specimens, to measure the tissue levels of malondialdehyde (MDA), protein carbonyl content (PCC), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and to evaluate the histologic changes.ResultsThere was a significant decrease in SOD and GPx levels, with an increase in MDA and PCC levels and intestinal mucosal injury in the intestinal I/R group (P < 0.05). Superoxide dismutase and GPx levels were significantly higher, MDA and PCC levels were significantly lower, and intestinal injury was significantly less severe in the I/R+α-LA+ebselen group than in the I/R group (P < 0.05). Although shortened villi and epithelial lifting were seen in the I/R group, only slight mucosal injury was seen in the treatment groups.Conclusionα-Lipoic acid and ebselen played an important role in attenuating I/R injury of the intestine by scavenging ROS and RNS.

Hyperbaric oxygen therapy reduces the severity of necrotizing enterocolitis in a neonatal rat model

INTRODUCTION Hyperbaric oxygen (HBO) therapy is known to increase oxygen concentration in tissues leading to induction of an adaptive increase in antioxidants, stimulation of angiogenesis, improvement of white blood cell action, and regulation of inflammatory process. Therefore, we tested the potential beneficial effect of HBO in neonatal rat model of necrotizing enterocolitis (NEC). MATERIALS AND METHODS Thirty newborn Sprague-Dawley rats, provided by the Experimental Research Council, Gulhane Military Medical Academy, Ankara,Turkey, were randomly divided into 3 groups as follows: NEC, NEC + HBO, and control. Necrotizing enterocolitis was induced by enteral formula feeding and exposure to hypoxia after cold stress at 4 degrees C and oxygen. The NEC + HBO group received HBO at 2.8 atmosphere absolute (ATA) for 90 minutes daily for 3 days. The pups were killed on the fourth day, and their intestinal tissues were harvested for biochemical and histopathologic analysis. Blood samples were also obtained from the pups. RESULTS The mortality rate was highest in the NEC group (3 pups in the NEC group vs 1 pup in the NEC + HBO group). Malondialdehyde and protein carbonyl content were significantly increased, whereas superoxide dismutase and glutathione peroxidase were significantly decreased in the NEC group. All these changes were similar to control levels in the NEC group by HBO treatment. Nitrate plus nitrite (NO(x)) levels and serum tumor necrosis factor alpha were increased in the NEC group and histopathologic injury score and apoptosis index in the NEC group were significantly higher than in the NEC + HBO group. CONCLUSION Hyperbaric oxygen significantly reduced the severity of NEC in our study.

Screening for retinopathy of prematurity in a tertiary care newborn unit in Turkey: frequency, outcomes, and risk factor analysis.

PURPOSE To report the frequency, risk factors, and outcomes of screening for retinopathy of prematurity (ROP). METHODS Data of neonates with a gestational age of 34 weeks or less were analyzed and the predictors on the development of ROP were determined by using logistic regression analysis. RESULTS Of the 318 neonates, the frequency of ROP was 37.1% for any stage and 7.2% for stage 3 or greater. Treatment was needed in 16.1% of neonates with ROP. No treatment was required in neonates with a gestational age of greater than 32 weeks. Oxygen therapy, sepsis, gestational age of 32 weeks or less, and birth weight of less than 1,250 g were determined as the independent risk factors. CONCLUSIONS Although frequency of ROP in Turkey is similar to that in the United States, the rate of severe ROP necessitating treatment seems to be higher in Turkey. Neonates with a gestational age of 32 weeks or less, a birth weight of less than 1,250 g, sepsis, and oxygen therapy may have a greater risk of developing ROP and screening should be intensified in the presence of these risk factors.

Protective effect of sulfhydryl-containing antioxidants against ischemia/reperfusion injury of prepubertal rat intestine

Background and Aim:  Reactive oxygen species generated during reperfusion of the tissue are known to play an important role in the basic pathophysiology of ischemia/reperfusion (I/R) injury. The aim of this study was to investigate and compare the protective effects of three sulfide‐based antioxidants, N‐acetylcysteine (NAC), erdosteine (ERD), and α‐lipoic acid (LA), on I/R injury of the small intestine tissue.

Endocan and Soluble Triggering Receptor Expressed on Myeloid Cells-1 as Novel Markers for Neonatal Sepsis

BACKGROUND Neonatal sepsis is an important cause of neonatal morbidity and mortality in the neonatal intensive care unit. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) has been evaluated in sepsis and septic shock, and it was found to be valuable in distinguishing septic cases from nonseptic cases. Endocan is constitutively expressed by endothelial cells, and high levels of endocan may be of relevance for the promotion of systemic inflammation. The aim of this study was to investigate whether the levels of sTREM-1 and endocan were increased in late-onset neonatal sepsis. METHODS Patients were classified into septic and nonseptic groups. Blood was collected from a peripheral vein of all septic newborns and healthy newborns at the time of initial laboratory evaluation before any treatment, and within 48-72 hours after initiation of treatment. Serum sTREM-1 and endocan measurements were performed when the study was finished. RESULTS The study population comprised of 50 neonates: 20 nonseptic neonates and 30 septic neonates. The groups were similar with regards to baseline characteristics. The initial measurements of interleukin-6 (IL-6), sTREM-1, endocan, and immature/total neutrophil ratio (I/T ratio) were significantly higher in septic neonates in comparison with nonseptic neonates. Receiver operating characteristic (ROC) curve analyses revealed that IL-6, sTREM-1, endocan, and I/T ratio resulted in significant areas under the curve (AUC) with respect to early identification of septic neonates. Soluble TREM-1 and IL-6 performed best to distinguish septic neonates from nonseptic neonates. Univariate logistic regression analysis showed that increased IL-6 and sTREM-1 were strong predictors of neonatal late-onset sepsis. CONCLUSION Serum sTREM-1, IL-6, endocan levels, and I/T ratio increased in septic neonates. However, the diagnostic accuracy of circulating sTREM-1 seemed to be better than endocan and I/T ratio, but lower than IL-6.

Serum and liver tissue biotinidase enzyme activity in rats which were administrated to valproic acid

Valproic acid (VPA) is an antiepileptic drug widely used and well-tolerated by most of patients. Its non-dose-dependent side effects seen mostly are the temporary gastrointestinal disturbances including anorexia and nausea, and hepatoxicity. As to its dose-dependent side effects are the weight loss, tremor, skin eruption and the alopecia. In this study we aimed to put forward the biotinidase deficiency considered as a possible cause of alopecia in the rats administered with valproic acid, and the correlation between liver and serum biotinidase enzyme activities (BEA) and transaminases, albumin and serum valproic acid levels. In our study, 4 groups of which one of them was a control group, each consisting of 15 male Wistar rats was organized. 200, 400, and 600 mg/kg/day of VPA, and distilled water, two divided doses per day, were administered per orally to VPA-1, VPA-2, VPA-3, and control group, respectively, in 60 days. Their serum and liver biotinidase enzyme activities, serum AST, ALT, albumin, and valproic acid levels were measured. Alopecia was seen in the subjects of 6.6% of VPA-1, 13.3% of VPA-2, and 26.6% of VPA-3. Significant difference in the liver tissues BEA was noted only between VPA-3 and the control group. Reductions were observed both in the liver tissues BEA and the serum BEA levels, which are inversely proportional to the VPA doses. A positive correlation between the liver biotinidase enzyme activities and the serum valproic acid levels, and the negative correlation between the liver tissues biotinidase activities and the serum valproic acid levels were noted, respectively. As a conclusion, the partial alopecia which is an initial symptom of reduced biotinidase activity may also be created depending on the reduction of biotinidase activity during valproic acid therapy. The alopecia which may further be observed in the patients receiving valproic acid therapy may be prevented by means of administration of biotin in a dose of 10 mg/day.

Toll-like receptor levels and caffeine responsiveness in rat pups during perinatal period.

Infants born prematurely are prone to bronchopulmonary dysplasia which is a devastating form of chronic lung disease that develops in very low birth weight infants. Toll-like receptors (TLRs) are pattern recognition receptors that initiate innate immune responses. We tested TLR2, 4, and 9 levels in the lungs of rat pups given caffeine at the first days of postnatal life. Twenty-four rat pups equally divided into three groups. The study group received caffeine immediately after birth for ten days. The levels of TLR9 were found significantly higher in study group than control groups. We conclude that the beneficial and anti-inflammatory effects of caffeine in the lungs of newborn rats may be due to increased TLR9 levels.

The Association between Serum 25-Hydroxy Vitamin D Level and Urine Cathelicidin in Children with a Urinary Tract Infection.

Objective: Cathelicidin is an important antimicrobial peptide in the urinary tract. Cathelicidin expression is strongly stimulated by 1,25-dihydroxy vitamin D in epithelial cells, macrophages/monocytes, and neutrophils. Vitamin D and cathelicidin status in children with urinary tract infection (UTI) caused by Escherichia coli is unknown. To establish the relationship between serum vitamin D and urine cathelicidin levels in children with a UTI caused by Escherichia coli. Methods: Serum 25-hydroxy vitamin D and urine cathelicidin levels were measured in 36 patients with UTI (mean age 6.8±3.6 years, range: 0.25-12.6 years) and 38 controls (mean age 6.3±2.8 years, range: 0.42-13 years). Results: There were no significant differences in urine cathelicidin levels between the study and control groups (p>0.05). Eight (22.2%) patients in the study group and 21 (58.3%) children in the control group were found to have sufficient vitamin D (≥20 ng/mL). Patients with sufficient vitamin D had higher urine cathelicidin levels than the controls with sufficient vitamin D (respectively 262.5±41.1 vs. 168±31.6 ng/mL, p=0.001). There were no significant differences between the patients and controls with insufficient vitamin D (p>0.05). Conclusion: The children with vitamin D insufficiency may not be able to increase their urine cathelicidin level during UTI caused by Escherichia coli. There is a need of prospective studies in order to prove a beneficial effect of vitamin D supplementation for the restoration of cathelicidin stimulation and consequently for prevention of UTI recurrence.