ID Number		1422
Study Type		In Vivo
Model		Turkish studies: 900, 1800 and 2450 MHz (GSM-like) exposure to rats and analysis of brain histopathology, oxidative stress and downstream effects on metabolism /hormones (TSH, T3, T4, melatonin), reproduction (testis morphology and function), bone mineralization, heart, blood and role of melatonin.
Details		Sprague-Dawley rats (n = 30) were exposed to 900 and 1800 MHz (CW) RF for 30 minutes / day, 5 days / week, for 2 weeks in restraining tubes at ~2 W/kg head average [assuming later reported SAR values applied to initial studies as well] and analyzed for various oxidative and metabolic parameters as well as subsequent effects on reproduction. In an initial study, the authors examined levels of nitric oxide (NO) in nasal passages (NO in the nose has apparent bacteriostatic and antiviral activities). All rats (including sham groups) were anesthetized with pentobarbital before being placed in the exposure apparatus (plastic restraining tube and a dipole antenna). One group of rats was also continually administered oral melatonin in the drinking water. The authors reported increase nitrous oxide levels with exposure. In related studies, rats (n=10 exposed, 10 controls) were exposed to 900 MHz (CW, GSM-like) RF at a power density of 1 +/- 0.4 mW/cm2 for 30 minutes/day, 5 days/week, for 4 weeks using a dipole antenna and a restrained exposure system. The authors report exposure had no effect on weight of testes, sperm count, or certain other reproductive endpoints in rats, but there was a decrease in serum testosterone in exposed animals compared to controls. The diameter of the seminiferous tubules was also significantly reduced in exposed animals. The authors suggest that RF exposure may cause biological effects on testes tissue, but it does not cause an adverse effect on spermatogenesis. In another study, rats exposed as above were found to have significantly lower blood TSH, T3, and T4 levels as assayed by RIA. In another recent study, exposure of rats as above for 10 days resulted in the generation of oxidative intermediates and tissue (kidney) damage (the kidney was apparently chosen as a target since (quote) users often wear mobile phones on their belts in proximity to the kidney and this organ is a major potential route for absorption of hazardous materials encountered in the environment (unquote)). The authors report and increase in reactive oxygen intermediates / lipid peroxidation (as assayed via malondialdehyde reactivity) and urine N-acetyl-beta-d-glucosaminidase (a marker of renal tubular damage) in kidney tissue. In addition, reductions in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were detected. The authors report reversal of these effects with treatment with the free radical scavenger melatonin. In another study, the authors report rats exposed as above, had <marginally lower> melatonin levels compared with sham-exposed animals although the results were not statistically significant. In a follow-on study, oxidative stress-induced impairment of kidney function in exposed rats (as determined by catalase, SOD, GSP-Px levels and urinary NAG, MDA and NO) was reversed by treatment with melatonin and caffeic acid phenethyl ester (CAPE, found in honeybee wax and claimed as an anti-oxidant, anti-inflammatory, anti-carcinogen, anti-viral, and immunomodulatory agent and a common folk medicine ingredient in the Middle East). A related pair of papers from the same lab (2006, 2009) reported that Wistar rats (n = 24) exposed to 900 MHz (GSM) for 30 minutes/day for one month at an estimated SAR of 0.016 - 4 W/kg (whole body) had increased oxidative stress level indicators (MDA assay of endometrial tissue,caspase-3, caspase-8, and Bax protein increases), and vitamin E and C (anti-oxidant) reversed this increase in oxidative endpoints due to RF exposure. AUTHORS' ABSTRACT: Eser, Ozguner et al. 2013 (IEEE #5423): AIm: The aim of this study is to determine the structural changes of electromagnetic waves in the frontal cortex, brain stem and cerebellum. Material and Methods: 24 Wistar Albino adult male rats were randomly divided into four groups: group I consisted of control rats, and groups II-IV comprised electromagnetically irradiated (EMR) with 900, 1800 and 2450 MHz. The heads of the rats were exposed to 900, 1800 and 2450 MHz microwaves irradiation for 1h per day for 2 months. Results: While the histopathological changes in the frontal cortex and brain stem were normal in the control group, there were severe degenerative changes, shrunken cytoplasm and extensively dark pyknotic nuclei in the EMR groups. Biochemical analysis demonstrated that the Total Antioxidative Capacity level was significantly decreased in the EMR groups and also Total Oxidative Capacity and Oxidative Stress Index levels were significantly increased in the frontal cortex, brain stem and cerebellum. IL-1² level was significantly increased in the EMR groups in the brain stem. Conclusion: EMR causes to structural changes in the frontal cortex, brain stem and cerebellum and impair the oxidative stress and inflammatory cytokine system. This deterioration can cause to disease including loss of these areas function and cancer development. AUTHORS' ABSTRACT: Ayata et al. 2004 (IEEE #5762): Most mobile phones emit 900 MHz of radiation that is mainly absorbed by the external organs. The effects of 900 MHz of radiation on fibrosis, lipid peroxidation, and anti-oxidant enzymes and the ameliorating effects of melatonin (Mel) were evaluated in rat skin. Thirty Wistar-Albino rats were used in the study. The experimental groups were the control group, the irradiated group (IR), and the irradiated+Mel treated group (IR+Mel). A dose of 900 MHz, 2 W radiation was applied to the IR group every day for 10 days (30 min/day). The IR+Mel group received 10 mg/kg/day melatonin in tap water for 10 days before the irradiation. At the end of the 10th day, a skin specimen was excised from the thoracoabdominal area. The levels of malondialdehyde (MDA) and hydroxypyroline and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were studied in the skin samples. MDA and hydroxyproline levels and activities of CAT and GSH-Px were increased significantly in the IR group compared to the control group (p<0.05) and decreased significantly in the IR+Mel group (p<0.05). SOD activity was decreased significantly in the IR group and this decrease was not prevented by the Mel treatment. These results suggest that rats irradiated with 900 MHz suffer from increased fibrosis and lipid peroxidation (LPO). Mel treatment can reduce the fibrosis and LPO caused by radiation. AUTHORS' ABSTRACT: Ozguner et al. 2006 (IEEE #5763): 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. AUTHORS' ABSTRACT: Turker et al. 2011 (IEEE #5764): The aim of this study was to investigate the possible protective role of selenium and L-carnitine on oxidative stress induced by 2.45-GHz radiation in heart of rat. For this purpose, 30 male Wistar Albino rats were equally divided into five groups namely controls, sham controls, radiation-exposed rats, radiation-exposed rats treated with intraperitoneal injections of sodium selenite at a dose of 1.5 mg/kg/day, and radiation-exposed rats treated with intraperitoneal injections of L-carnitine at a dose of 1.5 mg/kg/day. Except for the controls and sham controls, the animals were exposed to 2.45-GHz radiation during 60 min/day for 28 days. The lipid peroxidation (LP) levels were higher in the radiation-exposed groups than in the control and sham control groups. The lipid peroxidation level in the irradiated animals treated with selenium and L-carnitine was lower than in those that were only exposed to 2.45-GHz radiation. The concentrations of vitamins A, C, and E were lower in the irradiated-only group relative to control and sham control groups, but their concentrations were increased in the groups treated with selenium- and L-carnitine. The activity of glutathione peroxidase was higher in the selenium-treated group than in the animals that were irradiated but received no treatment. The erythrocyte-reduced glutathione and ²-carotene concentrations did not change in any of the groups. In conclusion, 2.45-GHz electromagnetic radiation caused oxidative stress in the heart of rats. There is an apparent protective effect of selenium and L-carnitine by inhibition of free radical formation and support of the antioxidant redox system. AUTHORS' ABSTRACT: Aynali et al. 2013 (IEEE #6170): It is well known that oxidative stress induces larynx cancer, although antioxidants induce modulator role on etiology of the cancer. It is well known that electromagnetic radiation (EMR) induces oxidative stress in different cell systems. The aim of this study was to investigate the possible protective role of melatonin on oxidative stress induced by Wi-Fi (2.45 GHz) EMR in laryngotracheal mucosa of rat. For this purpose, 32 male rats were equally categorized into four groups, namely controls, sham controls, EMR-exposed rats, EMR-exposed rats treated with melatonin at a dose of 10 mg/kg/day. Except for the controls and sham controls, the animals were exposed to 2.45 GHz radiation during 60 min/day for 28 days. The lipid peroxidation levels were significantly (p < 0.05) higher in the radiation-exposed groups than in the control and sham control groups. The lipid peroxidation level in the irradiated animals treated with melatonin was significantly (p < 0.01) lower than in those that were only exposed to Wi-Fi radiation. The activity of glutathione peroxidase was lower in the irradiated-only group relative to control and sham control groups but its activity was significantly (p < 0.05) increased in the groups treated with melatonin. The reduced glutathione levels in the mucosa of rat did not change in the four groups. There is an apparent protective effect of melatonin on the Wi-Fi-induced oxidative stress in the laryngotracheal mucosa of rats by inhibition of free radical formation and support of the glutathione peroxidase antioxidant system. AUTHORS' ABSTRACT: Gumral et al. 2009 (IEEE #6171): The levels of blood lipid peroxidation, glutathione peroxidase, reduced glutathione, and vitamin C were used to follow the level of oxidative damage caused by 2.45 GHz electromagnetic radiation in rats. The possible protective effects of selenium and L-carnitine were also tested and compared to untreated controls. Thirty male Wistar Albino rats were equally divided into five groups, namely Groups A1 and A2: controls and sham controls, respectively; Group B: EMR; Group C: EMR + selenium, Group D: EMR + L-carnitine. Groups BD were exposed to 2.45 GHz electromagnetic radiation during 60 min/ day for 28 days. The lipid peroxidation levels in plasma and erythrocytes were significantly higher in group B than in groups A1 and A2 (p<0.05), although the reduced glutathione and glutathione peroxidase values were slightly lower in erythrocytes of group B compared to groups A1 and A2. The plasma lipid peroxidation level in group A2 was significantly lower than in group B (p<0.05). Erythrocyte reduced glutathione levels (p<0.01) in group B; erythrocyte glutathione peroxidase activity in group A2 (p<0.05), group B (p<0.001), and group C (p<0.05) were found to be lower than in group D. In conclusion, 2.45 GHz electromagnetic radiation caused oxidative stress in blood of rat. L-carnitine seems to have protective effects on the 2.45-GHz-induced blood toxicity by inhibiting free radical supporting antioxidant redox system although selenium has no effect on the investigated values. AUTHORS' ABSTRACT: Kuybulu et al. 2016 (IEEE #6314): Purpose The aim of the present study was to investigate oxidative stress and apoptosis in kidney tissues of male Wistar rats that pre- and postnatally exposed to wireless electromagnetic field (EMF) with an internet frequency of 2.45 GHz for a long time. Methods The study was conducted in three groups of rats which were pre-natal, post-natal. and sham exposed groups. Oxidative stress markers and histological evaluation of kidney tissues were studied. Results Renal tissue malondialdehyde (MDA) and total oxidant (TOS) levels of pre-natal group were high and total antioxidant (TAS) and superoxide dismutase (SOD) levels were low. Spot urine NAG/creatinine ratio was significantly higher in pre- and post-natal groups (p < 0.001). Tubular injury was detected in most of the specimens in post-natal groups. Immunohistochemical analysis showed low-intensity staining with Bax in cortex, high-intensity staining with Bcl-2 in cortical and medullar areas of pre-natal group (p values, 0.000, 0.002, 0.000, respectively) when compared with sham group. Bcl2/Bax staining intensity ratios of medullar and cortical area was higher in pre-natal group than sham group (p = 0.018, p = 0.011). Conclusion Based on this study, it is thought that chronic pre- and post-natal period exposure to wireless internet frequency of EMF may cause chronic kidney damages; staying away from EMF source in especially pregnancy and early childhood period may reduce negative effects of exposure on kidney.
Findings		Effects
Status		Completed With Publication
Principal Investigator		Haydarpasa State Hospital, Istanbul, Turkey
Funding Agency		?????
Country		TURKEY
References		Koyu, A et al. Toxicol Ind Health, (2009) 25:429-434 Oral, B et al. Adv Ther, (2006) 23:957-973 Ozguner, F et al. Toxicol Ind Health, (2005) 21:223-230 Ozguner, F et al. Mol Cell Biochem, (2005) 276:31-37 Ozguner, F et al. Molec Cell Biochem, (2005) 277:73-80 Koyu, A et al. Toxicol Lett, (2005) 157:257-262 Koyu, A et al. Toxicol Ind Health, (2005) 21:27-31 Yariktas, M et al. Otolaryngol Head Neck Surg, (2005) 132:713-716 Oktem, F et al. Arch Med Res, (2005) 36:350-355 Ozguner, M et al. Saudi Medical Journal, (2005) 26:405-410 Ozguner, F et al. Toxicol Ind Health, (2004) 20:133-139 Ilhan, A et al. Clinical Chimica Acta., (2004) 340:153-162 Eser, O et al. Turkish Neurosurgery., (2013) 23:707-715 Ayata, A et al. J Dermatol., (2004) 31:878-883 Ozguner, F et al. Mol Cell Biochem, (2006) 282:83-88 Turker, Y et al. Biol Trace Elem Res., (2011) 143:1640-1650 Aynali, G et al. Eur Arch Otorhinolaryngol., (2013) 270:1695-1700 Gumral, N et al. Biol Trace Elem Res., (2009) 132:153-163 Kuybulu, AE et al. Ren Fail., (2016) 38:571-580 Postaci, I et al. Bratisl Med J., (2018) 119:481-489 Eser, O et al. Journal of Neurological Sciences [Turkish]. , (2012) 29:92-100 Ceyhan, AM et al. Arch Dermatol Res., (2012) 304:521-527 Gumral, N et al. Bratisl Lek Listy. , (2016) 117:665-671 Er, H et al. Reprod Sci., (2022) 29:1471-1485
Comments		No exposure assessment in initial studies (only provided in the 2005 papers), although in later studies the authors report that the ~2 W/kg head average exposure was associated with variations of up to 4 W/kg (local), and a 0.016 W/kg whole body average SAR. In the first study (NO), the authors mention the rats were also used in an experiment involving vision, but not whether this took place before, after, or during the RF experiment. Exposure in the author's system was also not specifically defined, and the authors report "the whole bodies of the rats were in close contact with the antenna (?), which operated at 2 W peak power with an average power density of 1.04 mW/cm2".