Mustafa Oran

Melatonin attenuates oxidative stress, liver damage and hepatocyte apoptosis after bile-duct ligation in rats.

The goal of this study was to evaluate the possible protective effects of melatonin against cholestatic oxidative stress, liver damage and hepatocyte apoptosis in the common rats with bile duct ligation (BDL). A total of 24 male Wistar albino rats were divided into three groups: control, BDL and BDL + received melatonin; each group contains eight animals. Melatonin-treated BDL rats received daily melatonin 100 mg/kg/day via intraperitoneal injection. The application of BDL clearly increased the malondialdehyde (MDA) levels and decreased the superoxide dismutase (SOD) and glutathione (GSH) activities. Melatonin treatment significantly decreased the elevated tissue MDA levels and increased the reduced SOD and GSH enzyme levels in the tissues. The changes demonstrate that the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells and neutrophil infiltration into the widened portal areas as observed in the BDL group. The data indicate that melatonin attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis. The α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the BDL were observed to be reduced with the melatonin treatment. These results suggest that administration of melatonin is a potentially beneficial agent to reduce liver damage in BDL by decreasing oxidative stress.

Asymmetric dimethylarginine contributes to airway nitric oxide deficiency in patients with COPD.

Asymmetric dimethylarginine (ADMA) and nitric oxide (NO) show their mechanism of action reciprocally, the balance between these molecules contributes to the tight regulation of airways tone and function.

Possible association between vitamin D deficiency and restless legs syndrome

Background and aim Restless legs syndrome (RLS) is a distressing sleep disorder that occurs worldwide. Although there have been recent developments in understanding the pathophysiology of RLS, the exact mechanism of the disease has not been well elucidated. An increased prevalence of neurologic and psychiatric diseases involving dopaminergic dysfunction in vitamin D–deficient patients led us to hypothesize that vitamin D deficiency might result in dopaminergic dysfunction and consequently, the development of RLS (in which dopaminergic dysfunction plays a pivotal role). Thus, the aim of this study was to evaluate the relationship between vitamin D deficiency and RLS. Methods One hundred and fifty-five consecutive patients, 18–65 years of age, who were admitted to the Department of Internal Medicine with musculoskeletal symptoms and who subsequently underwent neurological and electromyography (EMG) examination by the same senior neurologist, were included in this study. The patients were divided into two groups according to serum 25-hydroxyvitamin D (25(OH)D) (a vitamin D metabolite used as a measure of vitamin D status) level: 36 patients with serum 25(OH)D levels ≥20 ng/mL comprised the normal vitamin D group, and 119 patients with serum 25(OH)D levels <20 ng/mL comprised the vitamin D deficiency group. The two groups were compared for the presence of RLS and associated factors. Results The two groups were similar in terms of mean age, sex, mean body mass index (BMI), and serum levels of calcium, phosphate, alkaline phosphatase (ALP), and ferritin. The presence of RLS was significantly higher in the vitamin D deficiency group (χ2=12.87, P<0.001). Regression analysis showed vitamin D deficiency and serum 25(OH)D level to be significantly associated with the presence of RLS (odds ratio [OR] 5.085, P<0.001 and OR 1.047, P=0.006, respectively). Conclusion The present study demonstrated a possible association between vitamin D deficiency and RLS. Given the dopaminergic effects of vitamin D, 25(OH)D depletion may lead to dopaminergic dysfunction and may have a place in the etiology of RLS. Prospective vitamin D treatment studies are needed to confirm this relationship and to evaluate the efficacy of vitamin D as a treatment for RLS patients.

The protective effects of ω-3 fatty acids on doxorubicin-induced hepatotoxicity and nephrotoxicity in rats

This study aims to evaluate the protective effects of ω-3 fatty acids (FAs) on doxorubicin (DOX)-induced hepatotoxicity and nephrotoxicity in rats. A total of 24 adult male Sprague Dawley rats were divided into three groups. Control group was given only saline by intragastric gavage. DOX group received DOX at the dose of 30 mg/kg intraperitoneally on day 28. DOX-ω-3 FA group was given as ω-3 FAs at the dose of 400 mg/kg daily by intragastric gavage for 30 days and received DOX at the dose of 30 mg/kg intraperitoneally on day 28. At the end of the 30-day experimental period, the serum, liver and kidney tissue specimens were taken from the animals by giving a general anesthesia. Glutathione (GSH) and malondialdehyde (MDA) levels in serum and GSH and MDA levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver and kidney tissues were measured spectrophotometrically. In our study, a significant increase in MDA levels was observed in rats when given a dose of DOX and a significant decrease in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues was determined when compared with control group. In addition, a significant decrease in MDA levels was observed in rats when a dose of ω-3 FAs was given with DOX and a significant increase was determined in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues, when compared with DOX group. We concluded that ω-3 FA had favorable effects in rat liver and kidney tissues by preventing oxidative damage.

The role of oxidants and reactive nitrogen species in irritable bowel syndrome: A potential etiological explanation

Background The aim of this study was to evaluate the plasma concentrations of malondialdehyde (MDA) and nitric oxide (NO) and the plasma activities of oxidant and antioxidant enzymes in patients with IBS. Material/Methods A total of 36 patients with IBS were included in the study. Thirty-five healthy subjects were selected to form the control group. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase (XO), adenosine deaminase (AD) activities, and malondialdehyde (MDA) and nitric oxide (NO) concentrations were studied in the serum samples of all patients and controls. Results Plasma XO and AD activities, and MDA and NO concentrations were significantly higher in IBS patients than in controls. The SOD, CAT, and GSH-Px activities in the serum of patients with IBS were significantly lower than that of controls. Conclusions These results suggest that lipid peroxidation and alterations in the oxidant-antioxidant enzymatic system may play a role in the pathogenesis of IBS. Increased lipid peroxidation in IBS may be related to an increase in NO level and XO activity and a decrease in antioxidant enzymes activities. In addition, increased AD activity may have a role in immunological changes of IBS patients.

Association Between Serum Fetuin-A levels, Carotid Artery Stiffness, and Intima–Media Thickness in Patients With Normotensive Obstructive Sleep Apnea Syndrome

Increased carotid intima–media thickness (cIMT) and stiffness, reflecting subclinical atherosclerosis, are associated with obstructive sleep apnea syndrome (OSAS). The relationship between serum fetuin-A, which inhibits ectopic calcification, and atherosclerosis is unclear. Therefore, we investigated the association between serum fetuin-A levels and carotid artery stiffness and cIMT in patients with normotensive OSAS (n = 50) and non-OSAS controls (n = 38). Compared with controls, there were lower fetuin-A levels (59.4 ± 6.5 vs 68.2 ± 5.8 ng/mL, P = .029), higher mean cIMT (0.73 ± 0.2 vs 0.63 ± 0.3 mm, P < .001), and greater stiffness (β) index (7.45 ± 0.9 vs 5.2 ± 0.7, P = .001) in the OSAS group. The cIMT and stiffness (β) index were inversely correlated with fetuin-A levels (r = −.324, P = .033; r = −.466, P < .001, respectively) and positively correlated with apnea hypopnea index (r = .498, P < .001; r = .422, P = .001, respectively) in the OSAS group. Decreased serum fetuin-A levels were associated with subclinical carotid atherosclerosis in patients with normotensive OSAS.

Neuroprotective effect of ebselen against intracerebroventricular streptozotocin-induced neuronal apoptosis and oxidative stress in rats

The goal of this study was to examine the neuroprotective effect of ebselen against intracerebroventricular streptozotocin (ICV-STZ)-induced oxidative stress and neuronal apoptosis in rat brain. A total of 30 adult male Sprague-Dawley rats were randomly divided into 3 groups of 10 animals each: control, ICV-STZ, and ICV-STZ treated with ebselen. The ICV-STZ group rats were injected bilaterally with ICV-STZ (3 mg/kg) on days 1 and 3, and ebselen (10 mg/kg/day) was administered for 14 days starting from 1st day of ICV-STZ injection to day 14. Rats were killed at the end of the study and brain tissues were removed for biochemical and histopathological investigation. Our results demonstrated, for the first time, the neuroprotective effect of ebselen on Alzheimer’s disease (AD) model in rats. Our present study, in ICV-STZ group, showed significant increase in tissue malondialdehyde levels and significant decrease in enzymatic antioxidants superoxide dismutase and glutathione peroxidase in the frontal cortex tissue. The histopathological studies in the brain of rats also supported that ebselen markedly reduced the ICV-STZ-induced histopathological changes and well preserved the normal histological architecture of the frontal cortex tissue. The number of apoptotic neurons was increased in frontal cortex tissue after ICV-STZ administration. Treatment of ebselen markedly reduced the number of degenerating apoptotic neurons. The study demonstrates the effectiveness of ebselen, as a powerful antioxidant, in preventing the oxidative damage and morphological changes caused by ICV-STZ in rats. Thus, ebselen may have a therapeutic value for the treatment of AD.

Rosuvastatin Decreases Mean Platelet Volume in Patients With Diabetes Mellitus

Statins have multiple effects (also known as pleiotropic effects) on inflammation, plaque stabilization, endothelial function, and hemostasis. We evaluated the effects of rosuvastatin on mean platelet volume (MPV)—a marker for platelet activity—in patients with diabetes mellitus (DM) on rosuvastatin medication. Patients (n = 178) who were to be prescribed high-intensity rosuvastatin were retrospectively enrolled according to their medical records. Baseline and 6-month biochemical tests, automated blood count, cell-volume analysis, and their cardiovascular risk factors were recorded. Rosuvastatin significantly reduced the MPV and the lipid parameters including total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C). However, there was no correlation between MPV and LDL-C before (r = −.66; P = .383) and after (r = −.112; P = .135) rosuvastatin treatment or between ΔMPV and ΔLDL-C after 40 mg rosuvastatin daily therapy (r = −.155; P = .073). Rosuvastatin significantly decreases the MPV as well as cholesterol levels. The antiplatelet activation properties of high-dose rosuvastatin treatment in patients with DM are not lipid dependent.

Protective effects of onion (Allium cepa) extract against doxorubicin-induced hepatotoxicity in rats

Background/aim: Doxorubicin (DOX) is a widely used and potent chemotherapeutic agent. However, serious dose-limiting toxicity through generation of free oxygen radicals is a commonly encountered clinical problem. The aim of the current study was to assess the protective role of onion (Allium cepa) extract (ACE) against DOX-induced hepatotoxicity in rats. Method: A total of 24 rats were randomly divided into 3 equal experimental groups: (1) DOX; (2) ACE + DOX; and (3) control groups. ACE was given orally as 1 mL of fresh ACE juice for 14 consecutive days followed by DOX injection. DOX was injected intraperitoneally in a single dose of 30 mg/kg body weight to induce hepatotoxicity, and the rats were killed after 48 h from injection. Control group was given saline only. Results: In the ACE pretreated group (ACE + DOX), serum aspartate transaminase, alanine transaminase, and tissue malondialdehyde and glutathione levels were significantly lower, while superoxide dismutase and glutathione peroxidase were higher compared with the DOX group. The histopathological examination of liver specimens revealed parenchymal necrosis, proliferation of biliary duct in DOX group; while ACE pretreatment provided marked reduction in these changes. Conclusion: Our study indicates that pretreatment with ACE protects against DOX-induced hepatotoxicity due to the antioxidant properties of ACE. Further studies on efficacy of antioxidant treatment by ACE in DOX-mediated toxicity and underlying mechanisms would provide a better explanation.

Serum fetuin-A levels are associated with carotid intima–media thickness in patients with normotensive chronic obstructive pulmonary disease

BACKGROUND There are contradictory reports about the relationship between fetuin-A and atherosclerotic process. Coronary artery disease is the most important cause of mortality in patients with chronic obstructive pulmonary disease (COPD). We aimed to investigate the association of serum fetuin-A level with mean carotid intima-media thickness (cIMT) and ankle-brachial index (ABI) in COPD. METHODS We evaluated the association of serum fetuin-A level, mean cIMT and ABI in normotensive subjects with COPD (n = 65) and with non-COPD (n = 50). RESULTS Fetuin-A level was significantly lower (63.5 ± 19.8 ng/mL, 72.9 ± 16.2 ng/mL, p = 0.035) and C-reactive protein level higher (4 [1-10] vs. 3 [1-12] mg/dL, p = 0.034) in COPD patients than the control group. Compared to controls, fetuin-A level was significantly lower (63.5 ± 19.8 ng/mL, 72.9 ± 16.2 ng/mL, p = 0.035) and mean cIMT higher (0.69 [0.50-0.98] vs. 0.62 [0.44-0.98] mm, p = 0.034, respectively) in the COPD group. There was a significant negative correlation between mean cIMT and fetuin-A levels (r = -0.320, p = 0.032). Age (b ± SE: 0.002 ± 0.001, p = 0.008) and fetuin-A (b ± SE: -0.002 ± 0.001, p = 0.035) were decisive for the mean cIMT. CONCLUSIONS There are increased cIMT values, decreased fetuin-A levels, but unchanged ABI values in patients with normotensive COPD. Age and fetuin-A were predictors for cIMT, while fetuin-A was negatively correlated with cIMT.