Selami Suleymanoglu

Resveratrol treatment protects against doxorubicin-induced cardiotoxicity by alleviating oxidative damage.

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.

Allopurinol improves endothelial function and reduces oxidant-inflammatory enzyme of myeloperoxidase in metabolic syndrome

ObjectiveIn this study, we tested in patients with metabolic syndrome whether allopurinol through decreasing oxidative stress improves endothelial function, and ameliorates inflammatory state represented by markers of myeloperoxidase, C-reactive protein (CRP) and fibrinogen.MethodsIn a randomized, double-blind fashion; subjects with metabolic syndrome were treated with allopurinol (n = 28) or placebo (n = 22) for one month. Before and after treatment, blood samples were collected and the flow-mediated dilation (FMD) and isosorbide dinitrate (ISDN)-mediated dilation of the brachial artery were performed.ResultsBaseline clinical characteristics of the allopurinol and placebo groups demonstrated no differences in terms of clinical characteristics, endothelial function and inflammatory markers. After the treatment with allopurinol, FMD was increased from 8.0 ± 0.5 % to 11.8 ± 0.6% (P < 0.01), but there were no change in the placebo group. In both groups, ISDN-mediated dilation is unaffected by the treatment. As a marker of oxidative stress, allopurinol significantly reduced malondialdehyde. Moreover, myeloperoxidase levels were reduced by the treatment with allopurinol (56.1 ± 3.4 ng/ml vs. 44.4 ± 2.4 ng/ml, P < 0.05) but there were no change in the placebo group. Surprisingly, neither CRP nor fibrinogen levels were affected by the treatment in both groups.ConclusionXanthine oxidoreductase inhibition by allopurinol in patients with metabolic syndrome reduces oxidative stress, improves endothelial function, ameliorates myeloperoxidase levels and does not have any effect on CRP and fibrinogen levels.

Vaspin and its correlation with insulin sensitivity indices in obese children

AIM The aim of this study was to assess the vaspin and adiponectin concentrations on markers of insulin sensitivity and obesity in pubertal obese children and adolescents. MATERIAL AND METHODS Plasma vaspin and adiponectin level and its relationships with body mass index standard deviation score (BMI-SDS), insulin sensitivity and lipids were analyzed in 33 pubertal obese children (19 girls and 14 boys) and 36 healthy control children (18 girls and 18 boys) aged 11-16 years. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) and fasting glucose-to-insulin ratio (FGIR). Plasma vaspin and adiponectin concentrations were determined with radioimmunoassay. RESULTS Mean vaspin levels were found significantly higher and inversely, adiponectin levels were found significantly lower in obese pubertal group than control subjects. Vaspin levels were positively correlated with BMI-SDS, triglycerides, fasting insulin and HOMA-IR and negatively correlated with adiponectin levels and FGIR. Adiponectin levels were positively correlated with high density lipoprotein-chloesterol, FGIR and negatively correlated with vaspin, BMI-SDS, fasting insulin and HOMA-IR. CONCLUSION We found higher vaspin and lower adiponectin levels in obese children and these adipokines were significantly correlated with insulin sensitivity indices in this age.

Resveratrol improves cardiovascular function and reduces oxidative organ damage in the renal, cardiovascular and cerebral tissues of two-kidney, one-clip hypertensive rats

Objectives  The putative protective effects of resveratrol against oxidative injury in the heart, kidney and brain tissues of rats induced with the two‐kidney, one‐clip (2K1C) hypertension model were investigated.

Melatonin improves cardiovascular function and ameliorates renal, cardiac and cerebral damage in rats with renovascular hypertension

Abstract:  The effect of melatonin was investigated in an angiotensin II‐dependent renovascular hypertension model in Wistar albino rats by placing a renal artery clip (two‐kidney, one‐clip; 2K1C), while sham rats did not have clip placement. Starting either on the operation day or 3 wk after the operation, the rats received melatonin (10 mg/kg/day) or vehicle for the following 6 wk. At the end of the nineth week, after blood pressure (BP) and echocardiographic recordings were obtained, plasma samples were obtained to assay lactate dehydrogenase (LDH), creatine kinase (CK), antioxidant capacity (AOC), asymmetric dimethylarginine (ADMA), and nitric oxide (NOx) levels. In the kidney, heart and brain tissues, malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) and Na+‐K+ ATPase activities were determined. 2K1C caused an increase in BP and left ventricular (LV) dysfunction. In hypertensive animals LDH, CK, ADMA levels were increased in plasma with a concomitant reduction in AOC and NOx. Moreover, hypertension caused a significant decrease in tissue SOD, CAT, and Na+, K+‐ATPase activities and glutathione content, while MDA levels and MPO activity were increased in all studied tissues. On the other hand, both melatonin regimens significantly reduced BP, alleviated oxidative injury and improved LV function. In conclusion, melatonin protected against renovascular hypertension‐induced tissue damage and improved cardiac function presumably due to both its direct antioxidant and receptor‐dependent actions, suggesting that melatonin may be of therapeutic use in preventing oxidative stress due to hypertension.

Apelin, vaspin, visfatin and adiponectin in large for gestational age infants with insulin resistance

OBJECTIVE To investigate the relation of circulating four adipokines (apelin, vaspin, visfatin, adiponectin) with markers of insulin sensitivity in large for gestational age (LGA) infants. PATIENTS AND METHODS Forty LGA infants (20 LGA born from diabetic mothers and 20 LGA born from non-diabetic mothers) and 34 appropriate for gestational age (AGA) infants were recruited. Hyperinsulinism and insulin resistance was evaluated using the homeostasis model assessment (HOMA-IR), fasting glucose-to-insulin ratio (FGIR), quantitative insulin-sensitivity check index (QUICK-I) from fasting samples. Plasma adiponectin and vaspin levels were determined by radioimmunoassay. Determination of visfatin and apelin levels was performed by enzyme immunoassay. RESULTS HOMA-IR, apelin and visfatin levels (p<0.001, p<0.001, p<0.001, respectively) were significantly elevated and adiponectin levels, FGIR and QUICK-I values. (p<0.001, p<0.001, p<0.05, respectively) were significantly lower in the LGA group. Vaspin levels were higher in the LGA group than AGA neonates without a significance. The LGA infants with diabetic mother had significantly higher visfatin, apelin, HOMA-IR values, fasting insulin levels and significantly lower adiponectin, FGIR, QUICK-I values. Apelin and visfatin were correlated positively, and adiponectin was correlated negatively with birthweight, HOMA-IR values and fasting insulin levels. CONCLUSION Based on the findings of this study, it is too difficult to explain relation between birthweight and these adipocytokines, but findings of high insulin, HOMA-IR, visfatin, apelin and low adiponectin levels in the LGA neonates showed that these adipocytokines can be used as a good predictor for metabolic syndrome.

Ghrelin Levels and Postnatal Growth in Healthy Infants 0-3 Months of Age

Objective: The effect of ghrelin on growth of the newborn has long been argued, but not fully clarified. In this study, we aimed to investigate the relationship between ghrelin levels and growth parameters in the first 3 months of life. Methods: The study included 60 babies (27 girls and 33 boys) born at gestational ages between 38-42 weeks. The newborns were divided into three groups according to the Lubchenco curves as: small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA). The relationship between ghrelin levels and growth parameters in the third month was investigated. Results: Ghrelin concentrations were significantly higher in SGA (2.4±2.6 ng/dL) babies than in AGA (1.3±0.9 ng/dL) and LGA (1.0±0.8 ng/dL) babies. The lowest ghrelin levels were in the LGA group. In SGA infants, ghrelin concentrations were inversely correlated with change in weight (r=-0.577; p=0.001), change in length (r=-0.361; p=0.005), and change in head circumference (r=-0.387; p=0.002). Conclusion: The results show that at age 3 months, SGA infants had higher ghrelin levels than AGA and LGA infants. Our findings indicate that ghrelin may be involved in the process of catch-up growth in these infants. Conflict of interest:None declared.

Posttreatment with Aminoguanidine Attenuates Renal Ischemia/Reperfusion Injury in Rats

Acute renal failure secondary to ischemia/reperfusion (I/R) injury is associated with significant mortality and morbidity. Aminoguanidine (AG), an inducible nitric oxide synthase inhibitor with antioxidant properties, has been reported beneficial in renal I/R injury. The aim of the present study was to investigate the effect of AG on renal I/R injury and compare the effectiveness of different AG treatment modalities. Sprague-Dawley rats were randomly assigned to one of four groups. The control group (n = 6) received sham operation. The I/R group (n = 6), AG-I group (n = 8), and AG-II group (n = 8) received bilateral renal ischemia for 45 min followed by 24 hours of reperfusion. The AG-I group received AG (50 mg/kg) intraperitoneally four hours and 10 minutes before the induction of ischemia. The AG-II group received AG (50 mg/kg) intraperitoneally four hours and 10 minutes after the initiation of reperfusion. Serum urea and creatinine levels increased significantly in the I/R and AG-I groups compared to the control group. Kidney samples from rats in the I/R and AG-I groups revealed severe tubular damage at histopathological examination. Posttreatment with AG significantly reduced serum urea and creatinine levels and improved histopathological lesions compared with the I/R group. Although pretreatment with AG failed to protect kidneys against I/R injury in this experimental model, posttreatment with AG attenuated renal dysfunction and histopathological changes after I/R injury.

Hyperbaric Oxygen Therapy Does Not Potentiate Doxorubicin‐Induced Cardiotoxicity in Rats

The current use of doxorubicin is regarded as an absolute contraindication for hyperbaric oxygen (HBO2) therapy because of the increased risk of cardiotoxicity. The aim of this study was to investigate whether additional exposure to HBO2 during the course of doxorubicin treatment would further increase the cardiotoxicity of doxorubicin in rats. Female Wistar rats were treated with either HBO2 (n = 10) or doxorubicin (n = 8) or a combination of both treatments (n = 10) for 4 consecutive weeks and followed up for an additional 4 weeks. Cardiomyopathy was evaluated using two-dimensional and M-mode echocardiography at baseline, at the fourth, sixth and eighth weeks, and by histopathological investigation of the rat hearts at the eighth week. Doxorubicin treatment significantly reduced ejection fraction and fractional shortening (P < 0.001) and caused severe histopathological injury (P < 0.05) indicating development of cardiotoxicity. Although the combination of doxorubicin and HBO(2) also markedly reduced ejection fraction and fractional shortening (P < 0.001), this reduction was significantly less than that of doxorubicin treatment (P < 0.05). HBO2 therapy also attenuated doxorubicin-induced histopathological changes in rat hearts (P < 0.05). HBO2 alone did not alter echocardiographic parameters or histopathological findings (P > 0.05). In conclusion, HBO2 therapy does not potentiate doxorubicin-induced cardiotoxicity in rats. Cardioprotection conferred by HBO2 against doxorubicin warrants further investigation.

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.