Fehmi Ozguner

N-acetylcysteine for the prevention of postoperative atrial fibrillation: a prospective, randomized, placebo-controlled pilot study

AIMS Oxidative stress has recently been implicated in the pathophysiology of atrial fibrillation (AF). The aim of the present study was to evaluate the effects of antioxidant agent N-acetylcysteine (NAC) on postoperative AF. METHODS AND RESULTS The population of this prospective, randomized, double-blind, placebo-controlled study consisted of 115 patients undergoing coronary artery bypass and/or valve surgery. All the patients were treated with standard medical therapy and were randomized to NAC group (n = 58) or placebo (saline, n = 57). An AF episode >5 min during hospitalization was accepted as endpoint. During follow-up period, 15 patients (15/115, 13%) had AF. The rate of AF was lower in NAC group compared with placebo group (three patients in NAC group [5.2%] and 12 patients in placebo group [21.1%] had postoperative AF; odds ratio [OR] 0.20; 95% confidence interval [CI] 0.05 to 0.77; P = 0.019). In the multivariable logistic regression analysis, independent predictors of postoperative AF were left atrial diameter (OR, 1.18; 95% CI, 1.06-1.31; P = 0.002) and the use of NAC (OR, 0.20; 95% CI, 0.04-0.91; P = 0.038). CONCLUSION The result of this study indicates that NAC treatment decreases the incidence of postoperative AF.

Mobile phone-induced myocardial oxidative stress: protection by a novel antioxidant agent caffeic acid phenethyl ester.

Electromagnetic radiation (EMR) or radiofrequency fields of cellular mobile phones may affect biological systems by increasing free radicals, which appear mainly to enhance lipid peroxidation, and by changing the antioxidant defense systems of human tissues, thus leading to oxidative stress. Mobile phones are used in close proximity to the heart, therefore 900 MHz EMR emitting mobile phones may be absorbed by the heart. Caffeic acid phenethyl ester (CAPE), one of the major components of honeybee propolis, was recently found to be a potent free radical scavenger and antioxidant, and is used in folk medicine. The aim of this study was to examine 900 MHz mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and the role of CAPE on myocardial tissue against possible oxidative damage in rats. Thirty rats were used in the study. Animals were randomly grouped as follows: sham-operated control group (N: 10) and experimental groups: (a) group II: 900 MHz EMR exposed group (N: 10); and (b) group III: 900 MHz EMR exposed+CAPE-treated group (N: 10). A 900 MHz EMR radiation was applied to groups II and III 30 min/day, for 10 days using an experimental exposure device. Malondialdehyde (MDA, an index of lipid peroxidation), and nitric oxide (NO, a marker of oxidative stress) were used as markers of oxidative stress-induced heart impairment. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status. In the EMR exposed group, while tissue MDA and NO levels increased, SOD, CAT and GSH-Px activities were reduced. CAPE treatment in group III reversed these effects. In this study, the increased levels of MDA and NO and the decreased levels of myocardial SOD, CAT and GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced heart tissue damage, and CAPE, via its free radical scavenging and antioxidant properties, ameliorates oxidative heart injury. These results show that CAPE exhibits a protective effect on mobile phone-induced and free radical mediated oxidative heart impairment in rats.

Protective effects of melatonin and caffeic acid phenethyl ester against retinal oxidative stress in long-term use of mobile phone: A comparative study

There are numerous reports on the effects of electromagnetic radiation (EMR) in various cellular systems. Melatonin and caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, were recently found to be potent free radical scavengers and antioxidants. Mechanisms of adverse effects of EMR indicate that reactive oxygen species may play a role in the biological effects of this radiation. The present study was carried out to compare the efficacy of the protective effects of melatonin and CAPE against retinal oxidative stress due to long-term exposure to 900 MHz EMR emitting mobile phones. Melatonin and CAPE were administered daily for 60 days to the rats prior to their EMR exposure during our study. Nitric oxide (NO, an oxidant product) levels and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of retinal oxidative stress in rats following to use of EMR. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in retinal tissue. Retinal levels of NO and MDA increased in EMR exposed rats while both melatonin and CAPE caused a significant reduction in the levels of NO and MDA. Likewise, retinal SOD, GSH-Px and CAT activities decreased in EMR exposed animals while melatonin and CAPE caused a significant increase in the activities of these antioxidant enzymes. Treatment of EMR exposed rats with melatonin or CAPE increased the activities of SOD, GSH-Px and CAT to higher levels than those of control rats. In conclusion, melatonin and CAPE reduce retinal oxidative stress after long-term exposure to 900 MHz emitting mobile phone. Nevertheless, there was no statistically significant difference between the efficacies of these two antioxidants against to EMR induced oxidative stress in rat retina. The difference was in only GSH-Px activity in rat retina. Melatonin stimulated the retinal GSH-Px activity more efficiently than CAPE did.

Active smoking causes oxidative stress and decreases blood melatonin levels

Oxidative effects via free radical generation in smokers have been widely investigated. They cause lipid peroxidation, oxidation of proteins and damage to mainly lung and other tissues. In humans, antioxidative capacity of serum is related to antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and melatonin. The effect of cigarette smoking on plasma levels of melatonin and antioxidant enzymes has not been established together yet. Also, it may not be clear if melatonin levels are affected by smoking and melatonin has a protective effect on cigarette smoking-induced free radical damage. The aim of this study is to investigate the relationship between smoking and antioxidant capacity including melatonin, a powerful endogenous antioxidant, and antioxidant enzymes in teenage girls who are active smokers. Additionally, malondialdehyde (MDA) levels were determined in those who have smoked at least one packet a day for three or more years. MDA levels have been used as a convenient index of the lipid peroxidation-related oxidative damage of tissues. Twenty-one young female active smokers who study at the School of Nursing and 21 nonsmoking students (as controls) at the same school were included in the study. The activities of two principal antioxidant enzymes SOD, GSH-Px and plasma levels of MDA were significantly increased but melatonin content of the blood was significantly decreased as compared to nonsmokers. In spite of an increase in antioxidant enzyme activities, MDA levels were slightly increased in smokers. This indicates that antioxidant self-defence mechanisms may not sufficiently protect the respiratory system from smoke-mediated oxidative injury. This result may be related to low melatonin levels in teenage female smokers. It seems that melatonin can reduce free radical damage to the respiratory system induced by cigarette smoke. Further experimental investigations with exogenous melatonin treatments will be needed.

Evaluation of the effects of cadmium on rat liver

AbstactCadmium is one of the most toxic pollutants in environment. Cadmium accumulation in blood affects the renal cortex and causes renal failure. In this study, we aimed to evaluate the effects of cadmium on rat liver tissue. Eighteen male albino rats aged ten weeks old were used in the study. 15 ppm of cadmium was administered to rats via consumption water daily. At the end of the 30th study day, the animals were killed under ether anesthesia. After the liver tissue samples were taken, histopathological and biochemical examinations were performed. Histopathologic changes have included vacuolar and granular degenerations in hepatocytes, heterochromatic nucleuses and sinusoidal and portal widenings. Central vein diameters were normal in cadmium exposed group. Whereas, there was statistically significant difference between two groups by means of sinusoidal (p< 0.001) and portal triad diameters (p< 0.01). Malondialdehyde (MDA) is an indicator of lipid peroxidation. In this study, MDA was used as a marker of oxidative stress-induced liver impairment in cadmium exposed rats. Superoxide dismutase (SOD) and catalase (CAT) activities were also measured to evaluate the changes in antioxidative system in liver tissues. Current findings showed that MDA levels were increased and SOD and CAT activities were decreased in cadmium exposed group compared to control group. The difference between two groups was statistically significant (pvalues: MDA,p< 0.01; CAT,p< 0.01 and SOD,p< 0.05). In conclusion, these findings suggest the role of oxidative mechanisms in cadmium-induced liver tissue damage

Endometrial apoptosis induced by a 900-MHz mobile phone: Preventive effects of vitamins E and C

Numerous reports have described the effects induced by an electromagnetic field (EMF) in various cellular systems. The purposes of this study were to examine oxidative stress that promotes production of reactive oxygen species induced by a 900-megahertz (MHz) mobile phone and the possible ameliorating effects of vitamins E and C on endometrial tissue against EMF-induced endometrial impairment and apoptosis in rats. Animals were randomly grouped as follows: (1) sham-operated control group (n=8), (2) 900 MHz EMF-exposed group (n=8; 30 min/d for 30 d), and (3) 900 MHz EMF-exposed group, treated with vitamins E and C (n=8; 50 mg/kg intramuscularly and 20 mg/kg body weight intraperitoneally before daily EMF exposure). Malondialdehyde (an index of lipid peroxidation) was used as a marker of oxidative stress-induced endometrial impairment; Bcl-2, Bax, caspase-3, and caspase-8 were assessed immunohistochemically. In this study, increased malondialdehyde levels in endometrial tissue and apoptosis illustrated the role of the oxidative mechanism induced by exposure to a 900-MHz mobile phone-like device and vitamins E and C; via free radical scavenging and antioxidant properties, oxidative tissue injury and apoptosis were ameliorated in rat endometrium. In conclusion, exposure to 900-MHz radiation emitted by mobile phones may cause endometrial apoptosis and oxidative stress, but treatment with vitamins E and C can diminish these changes and may have a beneficial effect in preventing endometrial changes in rats.

900 MHz radiofrequency-induced histopathologic changes and oxidative stress in rat endometrium: protection by vitamins E and C

There are numerous reports on the effects of electromagnetic radiation (EMR) in various cellular systems. Mechanisms of adverse effects of EMR indicate that reactive oxygen species (ROS) may play a role in the biological effects of this radiation. The aims of this study were to examine 900 MHz mobile phone-induced oxidative stress that promotes production of ROS and to investigate the role of vitamins E and C, which have antioxidant properties, on endometrial tissue against possible 900MHz mobile phone-induced endometrial impairment in rats. The animals were randomly grouped (eight each) as follows: 1) Control group (without stress and EMR, Group I), 2) sham-operated rats stayed without exposure to EMR (exposure device off, Group II), 3) rats exposed to 900MHz EMR (EMR group, Group III) and 4) a 900MHz EMR exposed + vitamin-treated group (EMR + Vit group, Group IV). A 900 MHz EMR was applied to EMR and EMR + Vit group 30min/day, for 30 days using an experimental exposure device. Endometrial levels of nitric oxide (NO, an oxidant product) and malondialdehyde (MDA, an index of lipid peroxidation), increased in EMR exposed rats while the combined vitamins E and C caused a significant reduction in the levels of NO and MDA. Likewise, endometrial superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities decreased in EMR exposed animals while vitamins E and C caused a significant increase in the activities of these antioxidant enzymes. In the EMR group histopathologic changes in endometrium, diffuse and severe apoptosis was present in the endometrial surface epithelial and glandular cells and the stromal cells. Diffuse eosinophilic leucocyte and lymphocyte infiltration were observed in the endometrial stroma whereas the combination of vitamins E and C caused a significant decrease in these effects of EMR. It is concluded that oxidative endometrial damage plays an important role in the 900 MHz mobile phone-induced endometrial impairment and the modulation of oxidative stress with vitamins E and C reduces the 900MHz mobile phone-induced endometrial damage both at biochemical and histological levels. Toxicology and Industrial Health 2007; 23: 411—420.

Lithium-induced renal toxicity in rats: Protection by a novel antioxidant caffeic acid phenethyl ester

Lithium carbonate used in the long-term treatment of manic-depressive illness has been reported to lead to progressive renal impairment in rats and humans. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygene species mediated oxidative stress in ischemia-reperfusion and toxic injuries. The beneficial effect CAPE on lithium-induced nephrotoxicity has not been reported yet. The purpose of this study was to examine a possible renoprotective effect of CAPE against lithium-induced nephrotoxicity in a rat model. Twenty-two adult male rats were randomly divided into three experimental groups, as follows: control group, lithium-treated group (Li), and lithium plus CAPE-treated group (Li+CAPE). Li were treated intraperitoneally (i.p.) with 25 mg/kg Li2CO3 solution in 0.9% NaCl twice daily for 4 weeks. CAPE was co-administered i.p. with a dose of 10 μM/kg/day for 4 weeks. Serum Li, blood urea nitrogen and plasma creatinine, urinary N-acetyl-β-D-glucosaminidase (NAG, a marker of renal tubular injury), and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in Li-treated rats. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Serum Li levels were found high in the Li and Li+CAPE groups. In Li-administrated rats, urinary NAG and renal MDA levels were increased according to control and Li+CAPE groups (p < 0.05). CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD, CAT and GSH-Px activities were decreased in Li-administrated animals; CAPE caused a significant increase in the activities of these antioxidant enzymes. In conclusion, CAPE treatment has a protective effect against Li-induced renal tubular damage and oxidative stress in a rat model.

Methotrexate-induced renal oxidative stress in rats : the role of a novel antioxidant caffeic acid phenethyl ester

The exact mechanisms of methotrexate-induced renal toxicity have not yet been determined. However, several hypotheses have been put forward, including oxidative stress. The aim of this study was to investigate the role of caffeic acid phenethyl ester (Caffeic Ester), a novel antioxidant, on methotrexate-induced renal oxidative stress in rats. Nineteen adult male rats were equally divided into three experimental groups as follows: control group, methotrexate-treated group, and methotrexate-/Caffeic Ester-treated group. A single dose of methotrexate (20 mg/kg) was administered intraperitoneally (ip). Caffeic Ester (10 mmol/kg) was administered ip, once daily for seven days. Malondialdehyde (MDA) levels (an index of lipid peroxidation) were used as a marker of oxidative stress-induced renal injury. Similarly, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined to evaluate the changes of antioxidant status in renal tissue. Methotrexate administration to control rats increased MDA levels (PB < 0.0001), but decreased SOD, CAT and GSH-Px activities in renal tissue (PB < 0.0001). Caffeic Ester-/methotrexate treatment caused a significant decrease in MDA levels (PB < 0.001), and caused an increase in SOD, CAT and GSH-Px activities when compared with methotrexate treatment alone (PB < 0.001, < 0.05, < 0.0001, respectively). In conclusion, methotrexate leads to a reduction in antioxidant enzymatic defense capacity and causes lipid peroxidation in renal tissue. Similarly, Caffeic Ester exhibits protective effects on methotrexate-induced renal oxidative impairment in rats.

A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It has been used in folk medicine for many years in Middle East countries. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine long-term applied 900 MHz emitting mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and, was to investigate the role of CAPE on kidney tissue against the possible electromagnetic radiation (EMR)-induced renal impairment in rats. In particular, the ROS such as superoxide and nitric oxide (NO) may contribute to the pathophysiology of EMR-induced renal impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels, urinary N-acetyl-β-d-glucosaminidase (NAG, a marker of renal tubular injury) and nitric oxide (NO, an oxidant product) levels were used as markers of oxidative stress-induced renal impairment and the success of CAPE treatment. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissue were determined to evaluate the changes of antioxidant status. The rats used in the study were randomly grouped (10 each) as follows: i) Control group (without stress and EMR), ii) Sham-operated rats stayed without exposure to EMR (exposure device off), iii) Rats exposed to 900 MHz EMR (EMR group), and iv) A 900 MHz EMR exposed + CAPE treated group (EMR + CAPE group). In the EMR exposed group, while tissue MDA, NO levels and urinary NAG levels increased (p < 0.0001), the activities of SOD, CAT, and GSH-Px in renal tissue were reduced (p < 0.001). CAPE treatment reversed these effects as well (p < 0.0001, p < 0.001 respectively). In conclusion, the increase in NO and MDA levels of renal tissue, and in urinary NAG with the decrease in renal SOD, CAT, GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced renal tissue damage, and CAPE, via its free radical scavenging and antioxidant properties, ameliorates oxidative renal damage. These results strongly suggest that CAPE exhibits a protective effect on mobile phone-induced and free radical mediated oxidative renal impairment in rats.