Ahmet Koyu

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

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.

Comparative analysis of the protective effects of melatonin and caffeic acid phenethyl ester (CAPE) on mobile phone-induced renal impairment in rat.

Melatonin and caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, were recently found to be potent free radical scavengers and antioxidants. There are a number of reports on the effects induced by electromagnetic radiation (EMR) in various cellular systems. 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 protective effects of melatonin and CAPE against 900 MHz EMR emitted mobile phone-induced renal tubular injury. Melatonin was administered whereas CAPE was given for 10 days before the exposure. 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 rats exposed to EMR. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Urinary NAG and renal MDA were increased in EMR exposed rats while both melatonin and CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD and GSH-Px activities were decreased in EMR exposed animals while melatonin caused a significant increase in the activities of these antioxidant enzymes but CAPE did not. Melatonin caused a significant decrease in urinary NAG activity and MDA levels which were increased because of EMR exposure. CAPE also reduced elevated MDA levels in EMR exposed renal tissue, but the effect of melatonin was more potent than that of CAPE. Furthermore, treatment of EMR exposed rats with melatonin increased activities of SOD and GSH-Px to higher levels than those of control rats. In conclusion, melatonin and CAPE prevent renal tubular injury by reducing oxidative stress and protect the kidney from oxidative damage induced by 900 MHz mobile phone. Nevertheless, melatonin seems to be a more potent antioxidant compared with CAPE in kidney. (Mol Cell Biochem 276: 31–37, 2005)

Prevention of mobile phone induced skin tissue changes by melatonin in rat: an experimental study:

Most of the mobile phones in Turkey emit 900 MHz radiation which is mainly absorbed by the skin and, to a lesser extent, muscle. The aim of this study was to investigate the effects the 900 MHz electromagnetic irradiation emitted by these devices on the induction of histopathologic changes in skin and the effect of melatonin (Mel) on any of these changes. Thirty male Wistar-Albino rats were used in the study. The experimental groups were composed of: a nontreated control group, an irradiated group (IR) without Mel and an irradiated with Mel treatment group (IR + Mel). 900 MHz radiation was applied to IR group for 10 days (30 min/day). The IR + Mel group received 10 mg/kg per day melatonin in tap water for 10 days before irradiation. At the end of the tenth day, the skin graft was excized from the thoraco-abdominal area. Histopathologic changes in skin were analyzed. In the IR group, increased thickness of stratum corneum, atrophy of epidermis, papillamatosis, basal cell proliferation, increased granular cell layer (hypergranulosis) in epidermis and capillary proliferation, impairment in collagen tissue distribution and separation of collagen bundles in dermis were all observed compared to the control group. Most of these changes, except hypergranulosis, were prevented with melatonin treatment. In conclusion, exposure to 900 MHz radiation emitted by mobile phones caused mild skin changes. Furthermore, melatonin treatment can reduce these changes and may have a beneficial effect to prevent 900 MHz mobile phone-induced rat skin changes.

The protective effect of caffeic acid phenethyl ester (CAPE) on oxidative stress in rat liver exposed to the 900 MHz electromagnetic field.

In this study, we aimed to investigate the possible protective effects of caffeic acid phenethyl ester (CAPE) on lipid peroxidation (LPO) and the activities of antioxidant enzymes in the liver of rats exposed to the 900 MHz electromagnetic field (EMF). EMF of cellular phones may affect biological systems by increasing free radical, which appear mainly to enhance LPO, and by changing the antioxidative activities of liver, thus leading to oxidative damage. CAPE, an active component of propolis extract, exhibits antioxidant properties and several studies suggest that supplementation with antioxidant can influence EMF exposure induced hepatotoxicity. Thirty male Sprague-Dawley rats were divided into three groups: control (n = 10), 900 MHz EMF (n = 10) and 900 MHz EMF + CAPE (n = 10). CAPE was injected intraperitoneally for 30 days before exposure to EMF. Liver tissue was removed to study the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), xanthine oxidase (XO) and the levels of LPO. The activities of XO, CAT and level of LPO increased in the 900 MHz electromagnetic field (EMF) group compared with the control group, although XO, CAT activities and LPO levels were decreased by 900 MHz EMF + CAPE administration. The activities of SOD and GSH-Px decreased in the 900 MHz EMF group compared with the control group, although their levels were increased by EMF + CAPE administration. It can be concluded that CAPE may prevent the 900 MHz EMF-induced oxidative changes in liver by strengthening the antioxidant defense system by reducing reactive oxygen species and increasing antioxidant enzyme activities.

Testicular apoptosis and histopathological changes induced by a 2.45 GHz electromagnetic field

There is a growing public concern about the potential human health hazard caused by exposure to electromagnetic radiation (EMR). The objective of this study is to investigate the effects of 2450 mhz electromagnetic field on apoptosis and histopathological changes on rat testis tissue. Twelve-week-old male Wistar Albino rats were used in this study. Eighteen rats equally divided into three different groups which were named group I, II and III. Cage control (group I), sham control (group II) and 2.45 GHz EMR (group III) groups were formed. Group III were exposed to 2.45 GHz EMR, at 3.21 W/kg specific absorption rate for 60 minutes/ day for 28 days. There was no difference among the groups for the diameter of the seminiferous tubules, pyknotic, karyolectic and karyotic cells. However, the number of Leydig cells of testis tissue of the rats in group III was significantly reduced comparing with the group I (p < 0.05). Estimation of spermatogenesis using the Johnsen testicular biopsy score revealed that the difference between groups is statistically significant. The level of TNF-α, Caspase-3 and Bcl-2 were compared, and no significant difference was found between the groups. When Bax apoptosis genes and Caspase-8 apoptosis enzyme were compared, there were significant differences between the groups (p < 0.05). Electromagnetic field affects spermatogenesis and causes to apoptosis due to the heat and other stress-related events in testis tissue.

N‐acetylcysteine modulates doxorubicin‐induced oxidative stress and antioxidant vitamin concentrations in liver of rats

Doxorubicin (DOX) is a chemotherapeutic agent, and is widely used in cancer treatment. The most common side effect of DOX was indicated on cardiovascular system by experimental studies. There are some studies suggesting oxidative stress‐induced toxic changes on liver related to DOX administration. The aim of the present study was to evaluate whether antioxidant N‐acetylcysteine (NAC) relieves oxidative stress in DOX‐ induced liver injury in rat. Twenty‐four male rats were equally divided into three groups. First group was used as a control. Second group received single dose of DOX. NAC for 10 days was given to constituting the third group after giving one dose of DOX. After 10 days of the experiment, liver tissues were taken from all animals. Lipid peroxidation (LP) levels were higher in the DOX group than in control whereas LP levels were lower in the DOX + NAC group than in control. Vitamin C and vitamin E levels were lower in the DOX group than in control whereas vitamin C and vitamin E levels were higher in the DOX + NAC group than in the DOX group. Reduced glutathione levels were higher in the DOX + NAC group than in control and DOX group. Glutathione peroxidase, vitamin A and β‐carotene values were not changed in the three groups by DOX and NAC administrations. In histopathological evaluation of DOX group, there were mononuclear cell infiltrations, vacuolar degeneration, hepatocytes with basophilic nucleus and sinusoidal dilatations. The findings were totally recovered by NAC administration. In conclusion, N‐acetylcysteine induced modulator effects on the doxorubicin‐induced hepatoxicity by inhibiting free radical production and supporting the antioxidant vitamin levels. Copyright

No effects of 900 MHz and 1800 MHz electromagnetic field emitted from cellular phone on nocturnal serum melatonin levels in rats

In this study, the effects of exposure to a 900 MHz and 1800 MHz electromagnetic field (EMF) on serum nocturnal melatonin levels of adult male Sprague-Dawley rats were studied. Thirty rats were used in three independent groups, 10 of which were exposed to 900 MHz, 10 of which were exposed to 1800 MHz and 10 of which were sham-exposed (control). The exposures were performed 30 min/day, for five days/week for four weeks to 900 MHz or 1800 MHz EMF. Control animals were kept under the same environmental conditions as the study groups except with no EMF exposure. The concentration of nocturnal melatonin in the rat serum was measured by using a radioimmunoassay method. There were no statistically significant differences in serum melatonin concentrations between the 900 MHz EMF group and the sham-exposed group (P-0.05). The values at 12:00 pm were 39.119 / 6.5 pg/mL in the sham-exposed group and 34.979 / 5.1 pg/mL in the 900 MHz EMF-exposed group. Also, there were no statistically significant differences in serum melatonin concentrations between the sham-exposed group and the 1800 MHz EMF-exposed group (P-0.05). The values at 12:00 pm were 39.119 / 6.5 pg/mL in the sham-exposed group and 37.969 / 7.4 pg/mL in the exposed group. These results indicate that mobile phones, emitting 900 and 1800 MHz EMF, have no effect on nocturnal serum melatonin levels in rats.

Caffeic Acid Phenethyl Ester Modulates 1800 MHz Microwave-Induced Oxidative Stress in Rat Liver

Microwaves (MW) from cellular phones may affect biological systems by increasing free radicals, which may enhance lipid peroxidation (LP), and by changing the antioxidative activities of the liver, thus leading to oxidative damage. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant properties and several studies suggest that supplementation with antioxidant can influence MW induced hepatotoxicity. The present study was designed to determine the effects of MW on the liver oxidant/antioxidant system, and the possible protective effects of CAPE on liver toxicity induced by MW. Twenty nine male Spraque- Dawley rats were divided into three groups: control (n = 9), 1800 MHz MW (n = 10) and 1800 MHz MW + CAPE (n = 10). CAPE was injected intraperitoneally for 30 days before exposure to MW. Liver tissue was removed to study the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), xanthine oxidase (XO) and the levels of LP. The activities of XO, CAT and level of LP increased in MW group compared with the control group although XO and LP levels were decreased by MW + CAPE administration. The activities of SOD and GSH-Px decreased in MW group compared with the control group. Their levels were increased by MW + CAPE administration. We conclude that CAPE may prevent MW-induced oxidative changes in liver by strengthening the antioxidant defense system, by reducing reactive oxygen species, and by increasing antioxidant enzyme activities.