Effect of 900 MHz radiofrequency radiation on oxidative stress in rat brain and serum

The increasing use of mobile telephones raises the question of possible adverse effects of the electromagnetic fields (EMF) that these phones produce. In this study, we examined the oxidative stress in the brain tissue and serum of rats that resulted from exposure to a 900-MHz EMF at a whole body average specific absorption rate (SAR) of 1.08 W/kg for 1 h/day for 3 weeks. We also examined the antioxidant effect of garlic powder (500 mg/kg/day) given orally to EMF-exposed rats. We found that malondialdehyde (MDA) (p < 0.001) and advanced oxidation protein product (AOPP) (p < 0.05) increased in rat brain tissue exposed to the EMF and that garlic reduced these effects (p < 0.05). There was no significant difference in the nitric oxide (NO) levels in the brain. Paraoxonase (PON) was not detected in the brain. There was a significant increase in the levels of NO (p < 0.001) detected in the serum after EMF exposure, and garlic intake did not affect this increase in NO. Our results suggest that there is a significant increase in brain lipid and protein oxidation after electromagnetic radiation (EMR) exposure and that garlic has a protective effect against this oxidative stress.     

Exposure to 900 MHz radiofrequency radiation induces caspase 3 activation in proliferating human lymphocytes

Palumbo, R., Brescia, F., Capasso, D., Sannino, A., Sarti, M., Capri, M., Grassilli, E. and Scarfì, M. R. Exposure to 900 MHz Radiofrequency Radiation Induces Caspase 3 Activation in Proliferating Human Lymphocytes. Radiat. Res. 170, 327- 334 (2008).In this study, the induction of apoptosis after exposure to 900 MHz radiofrequency radiation (GSM signal) was investigated by assessing caspase 3 activation in exponentially growing Jurkat cells and in quiescent and proliferating human peripheral blood lymphocytes (PBLs). The exposure was carried out at an average specific absorption rate of 1.35 W/kg in a dual wire patch cell exposure system where the temperature of cell cultures was accurately controlled. After 1 h exposure to the radiofrequency field, a slight but statistically significant increase in caspase 3 activity, measured 6 h after exposure, was observed in Jurkat cells (32.4%) and in proliferating human PBLs (22%). In contrast, no effect was detected in quiescent human PBLs. In the same experimental conditions, apoptosis was also evaluated in Jurkat cells by Western blot analysis and in both cell types by flow cytometry. To evaluate late effects due to caspase 3 activity, flow cytometry was also employed to assess apoptosis and viability 24 h after radiofrequency-radiation exposure in both cell types. Neither the former nor the latter was affected. Since in recent years it has been reported that caspases are also involved in processes other than apoptosis, additional cell cycle studies were carried out on proliferating T cells exposed to radiofrequency radiation; however, we found no differences between sham-exposed and exposed cultures. Further studies are warranted to investigate the biological significance of our findings of a dose-response increase in caspase 3 activity after exposure to radiofrequency radiation.     

Proliferation, oxidative stress and cell death in cells exposed to 872 MHz radiofrequency radiation and oxidants

Human SH-SY5Y neuroblastoma and mouse L929 fibroblast cells were exposed to 872 MHz radiofrequency (RF) radiation using continuous waves (CW) or a modulated signal similar to that emitted by GSM mobile phones at a specific absorption rate (SAR) of 5 W/kg in isothermal conditions. To investigate possible combined effects with other agents, menadione was used to induce reactive oxygen species, and tert-butylhydroperoxide (t-BOOH) was used to induce lipid peroxidation. After 1 or 24 h of exposure, reduced cellular glutathione levels, lipid peroxidation, proliferation, caspase 3 activity, DNA fragmentation and viability were measured. Two statistically significant differences related to RF radiation were observed: Lipid peroxidation induced by t-BOOH was increased in SH-SY5Y (but not in L929) cells, and menadione-induced caspase 3 activity was increased in L929 (but not in SH-SY5Y) cells. Both differences were statistically significant only for the GSM-modulated signal. The other end points were not significantly affected in any of the experimental conditions, and no effects were observed from exposure to RF radiation alone. The positive findings may be due to chance, but they may also reflect effects that occur only in cells sensitized by chemical stress. Further studies are required to investigate the reproducibility and dose response of the possible effects.     

Effect of 900-, 1800-, and 2100-MHz radiofrequency radiation on DNA and oxidative stress in brain

Ubiquitous and ever increasing use of mobile phones led to the growing concern about the effects of radiofrequency radiation (RFR) emitted by cell phones on biological systems. The aim of this study is to explore whether long-term RFR exposure at different frequencies affects DNA damage and oxidant-antioxidant parameters in the blood and brain tissue of rats. 28 male Sprague Dawley rats were randomly divided into four equal groups (n = 7). They were identified as Group 1: sham-control, Group 2: 900 MHz, Group 3: 1800 MHz, and Group 4: 2100 MHz. Experimental groups of rats were exposed to RFR 2 h/day for 6 months. The sham-control group of rats was subjected to the same experimental condition but generator was turned off. Specific absorption rates (SARs) at brain with 1 g average were calculated as 0.0845 W/kg, 0.04563 W/kg, and 0.03957, at 900 MHz, 1800 MHz, and 2100 MHz, respectively. Additionally, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), total antioxidant status (TAS), and total oxidant status (TOS) analyses were conducted in the brain tissue samples. Results of the study showed that DNA damage and oxidative stress indicators were found higher in the RFR exposure groups than in the sham-control group. In conclusion, 900-, 1800-, and 2100-MHz RFR emitted from mobile phones may cause oxidative damage, induce increase in lipid peroxidation, and increase oxidative DNA damage formation in the frontal lobe of the rat brain tissues. Furthermore, 2100-MHz RFR may cause formation of DNA single-strand breaks.     

Impacts of exposure to 900 MHz mobile phone radiation on liver function in rats

Objective: To study the impacts of exposure to electromagnetic radiation(EMR) on liver function in rats. Methods: Twenty adult male Sprague-Dawley rats were randomly divided into normal group and radiated group. The rats in normal group were not radiated, those in radiated group were exposed to EMR 4 h/d for 18 consecutive days. Rats were sacrificed immediately after the end of the experiment. The serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST), and those of malondialdehyde(MDA) and glutathione(GSH) in liver tissue were evaluated by colorimetric method. The liver histopathological changes were observed by hematoxylin and eosin staining and the protein expression of bax and bcl-2 in liver tissue were detected by immunohistochemical method. Terminal-deoxynucleotidyl transferase mediated nick and labelling(TUNEL) method was used for analysis of apoptosis in liver. Results: Compared with the normal rats, the serum levels of ALT and AST in the radiated group had no obvious changes(P0.05), while the contents of MDA increased(P0.01) and those of GSH decreased(P0.01) in liver tissues. The histopathology examination showed diffuse hepatocyte swelling and vacuolation, small pieces and focal necrosis. The immunohistochemical results displayed that the expression of the bax protein was higher and that of bcl-2 protein was lower in radiated group. The hepatocyte apoptosis rates in radiated group was higher than that in normal group(all P0.01). Conclusion: The exposure to 900 MHz mobile phone 4 h/d for 18 days could induce the liver histological changes, which may be partly due to the apoptosis and oxidative stress induced in liver tissue by electromagnetic radiation.     

Aortic coarctation induces oxidative stress in rat tissues

The purpose of this study was to evaluate the induction of oxidative stress in heart and erythrocytes from rats with abdominal aorta coarctation (Coa) compared with sham-operated normotensive controls (Sham). The group of Coa animals developed myocardial hypertrophy, showing heart homogenates markedly increased levels of reduced glutathione (48%), lipid peroxidation (148%) and activation of superoxide dismutase and glutathione peroxidase (189% and 37%, respectively), compared with controls. Other oxidative stress indicators were also altered in erythrocytes from Coa rats: increased protein carbonyl content (141%) and total glutathione level (349%) were determined. Inactivation of the antioxidant enzymes catalase (27%), superoxide dismutase (58%) and glutathione peroxidase (25%) was observed in erythrocytes from the Coa group. Taken jointly our results provide strong evidence for the production of oxidative stress in heart and erythrocytes from aortic coarcted rats.     

Diethyldithiocarbamate injection induces transient oxidative stress in goldfish tissues

The effects of intraperitoneal injection of diethyldithiocarbamate (DDC) on free radical processes were examined in brain, liver and kidney of goldfish (Carassius auratus). Levels of oxidatively modified lipids and proteins as well as the activities of antioxidant and associated enzymes were measured. Intraperitoneal injection of DDC at a concentration of 0.01 mg/g wet mass decreased SOD activities by about 30-50% after 48 and 168 h compared to corresponding sham-injected values. This treatment resulted in transient oxidative stress. Lipid peroxide content increased after DDC injection at all time points in the kidney, after 48 h in the liver and was elevated in most experimental groups in the brain. Thiobarbituric-acid reactive substances (end products of lipid peroxidation) rose within the first 48 h after injection, but returned to initial levels after 168 h. Two other indices of oxidative stress were also transiently modified: protein carbonyl levels in the brain and kidney increased 24h post-injection, and the low-molecular mass thiol content was reduced over the same period in all tissues examined. Activities of catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and glucose-6-phosphate dehydrogenase showed differential responses to DDC treatment that rebounded by 168 h post-injection. Glutathione peroxidase activities were reduced by 60, 45 and 65% in the brain, liver and kidney, respectively, after 24h but rebounded thereafter. After 48 h post-injection with DDC significant decreases were also seen in liver and kidney catalase, GST activities in all three tissues, and kidney GR and G6PDH activities. In some cases, catalase, GST, GR and G6PDH activities transiently increased after 24 h. It was concluded that DDC injection depleted SOD and simultaneously stimulated lipid peroxidation, but did not require compensatory enhancement of other enzymatic defenses. Different actions of the superoxide anion in cellular metabolism and possible consequences of the impairment of superoxide dismutase are discussed.     

Cytogenetic studies in human cells exposed in vitro to GSM-900 MHz radiofrequency radiation using R-banded karyotyping

It is important to determine the possible effects of exposure to radiofrequency (RF) radiation on the genetic material of cells since damage to the DNA of somatic cells may be linked to cancer development or cell death and damage to germ cells may lead to genetic damage in next and subsequent generations. The objective of this study was to investigate whether exposure to radiofrequency radiation similar to that emitted by mobile phones of second-generation standard Global System for Mobile Communication (GSM) induces genotoxic effects in cultured human cells. The cytogenetic effects of GSM-900 MHz (GSM-900) RF radiation were investigated using R-banded karyotyping after in vitro exposure of human cells (amniotic cells) for 24 h. The average specific absorption rate (SAR) was 0.25 W/kg. The exposures were carried out in wire-patch cells (WPCs) under strictly controlled conditions of temperature. The genotoxic effect was assessed immediately or 24 h after exposure using four different samples. One hundred metaphase cells were analyzed per assay. Positive controls were provided by using bleomycin. We found no direct cytogenetic effects of GSM-900 either 0 h or 24 h after exposure. To the best of our knowledge, our work is the first to study genotoxicity using complete R-banded karyotyping, which allows visualizing all the chromosomal rearrangements, either numerical or structural.     

Comparison of bioactivity between GSM 900 MHz and DCS 1800 MHz mobile telephony radiation

An increasing number of studies find that pulsed Radio Frequency (RF), electromagnetic radiation of both systems of digital mobile telephony, established and commonly used in Europe during the last years, GSM 900 MHz (Global System for Mobile telecommunications) and DCS 1800 MHz (Digital Cellular System), exert intense biological action on different organisms and cells (Hardell et al., 2006; Hyland, 2000; Kundi, 2004; Panagopoulos et al., 2004, 2007). The two types of cellular telephony radiation use different carrier frequencies and give different frequency spectra, but they usually also differ in intensity, as GSM 900 MHz antennas operate at about double the power output than the corresponding DCS 1800 MHz ones. In our present experiments, we used a model biological system, the reproductive capacity of Drosophila melanogaster, to compare the biological activity between the two systems of cellular mobile telephony radiation. Both types of radiation were found to decrease significantly and non thermally the insect's reproductive capacity, but GSM 900 MHz seems to be even more bioactive than DCS 1800 MHz. The difference seems to be dependent mostly on field intensity and less on carrier frequency.     

The prophylactic effect of vitamin C on induced oxidative stress in rat testis following exposure to 900 MHz radio frequency wave generated by a BTS antenna model

Radio frequency wave (RFW) generated by base transceiver station (BTS) has been reported to make deleterious effects on reproduction, possibly through oxidative stress. This study was conducted to evaluate the effect of RFW generated by BTS on oxidative stress in testis and the prophylactic effect of vitamin C by measuring the antioxidant enzymes activity, including glutathione peroxidase, superoxide dismutase (SOD) and catalase, and malondialdehyde (MDA). Thirty-two adult male Sprague–Dawley rats were randomly divided into four experimental groups and treated daily for 45 days as follows: sham, sham+vitamin C (l-ascorbic acid 200 mg/kg of body weight/day by gavage), RFW (exposed to 900 MHz RFW) ‘sham’ and ‘RFW’ animals were given the vehicle, i.e., distilled water and the RFW+vitamin C group (received vitamin C in addition to exposure to RFW). At the end of the experiment, all the rats were sacrificed and their testes were removed and used for measurement of antioxidant enzymes and MDA activity. The results indicate that exposure to RFW in the test group decreased antioxidant enzymes activity and increased MDA compared with the control groups (p < 0.05). In the treated group, vitamin C improved antioxidant enzymes activity and reduced MDA compared with the test group (p < 0.05). It can be concluded that RFW causes oxidative stress in testis and vitamin C improves the antioxidant enzymes activity and decreases MDA.     

Protective effects of luteolin on rat testis following exposure to 900 MHz electromagnetic field

Increasing cell phone use calls for clarification of the consequences of long term exposure to electromagnetic fields (EMF). We investigated the effects of EMF on the testes of 12-week-old rats as well as possible protective effects of luteolin on testis tissue. Twenty-four Wistar albino rats were randomly divided into four groups: control, EMF, luteolin, and EMF + luteolin. The number of Leydig cells, primary spermatocytes and spermatids were reduced in the EMF group compared to the control group. In the EMF + luteolin group, the number of Leydig cells, primary spermatocytes and spermatids was significantly greater than the EMF group. We found an increase in superoxide dismutase (SOD) activity in the EMF group compared to the control group. In the EMF group, we found decreased wet weight of testes and serum testosterone levels compared to the control group. Decreased SOD enzyme activity, and increased serum testosterone levels and weight of the testes were observed in the EMF + luteolin group compared to the EMF group. EMF also affected sperm morphology. We found that in rat testis repeated exposure to 900 MHz EMF caused changes in testicular tissue and that the antioxidant, luteolin, substantially reduced the deleterious effects of EMF.     

Evaluation of oxidative stress and genotoxicity of 900 MHz electromagnetic radiations using Trigonella foenum-graecum test system

Protoplasma - Unprecedented growth in the communication sector and expanded usage of the number of wireless devices in the past few decades have resulted in a tremendous increase in emissions of...     

Radiofrequency radiation (900 MHz) induces Egr-1 gene expression and affects cell-cycle control in human neuroblastoma cells

Many environmental signals, including ionizing radiation and UV rays, induce activation of Egr-1 gene, thus affecting cell growth and apoptosis. The paucity and the controversial knowledge about the effect of electromagnetic fields (EMF) exposure of nerve cells prompted us to investigate the bioeffects of radiofrequency (RF) radiation on SH-SY5Y neuroblastoma cells. The effect of a modulated RF field of 900 MHz, generated by a wire patch cell (WPC) antenna exposure system on Egr-1 gene expression, was studied as a function of time. Short-term exposures induced a transient increase in Egr-1 mRNA level paralleled with activation of the MAPK subtypes ERK1/2 and SAPK/JNK. The effects of RF radiations on cell growth rate and apoptosis were also studied. Exposure to RF radiation had an anti-proliferative activity in SH-SY5Y cells with a significant effect observed at 24 h. RF radiation impaired cell cycle progression, reaching a significant G2-M arrest. In addition, the appearance of the sub-G1 peak, a hallmark of apoptosis, was highlighted after a 24-h exposure, together with a significant decrease in mRNA levels of Bcl-2 and survivin genes, both interfering with signaling between G2-M arrest and apoptosis. Our results provide evidence that exposure to a 900 MHz-modulated RF radiation affect both Egr-1 gene expression and cell regulatory functions, involving apoptosis inhibitors like Bcl-2 and survivin, thus providing important insights into a potentially broad mechanism for controlling in vitro cell viability.     

Hypoxia induces oxidative stress in tissues of a goby, the rotan Perccottus glenii

The effects of hypoxia (0.4 mg O₂/L) for 2, 6 or 10 h and subsequent normoxic recovery on the levels of lipid peroxides, thiobarbituric acid reactive substances, protein carbonyls (CP), free thiols, and the activities of six antioxidant and associated enzymes were measured in the brain, liver, and skeletal muscle of the rotan Perccottus glenii. Hypoxia increased CP content in the brain (5.0–7.4-fold), liver (2.2–3.3-fold) and muscle (3.2–61-fold) relative to controls and the levels remained elevated during recovery. Lipid peroxide content rose within 2 h of hypoxia in all tissues examined with the most marked increase (8.7-fold) in the liver, but decreased again during longer hypoxic exposure except in the muscle. Levels of low-molecular mass thiols were transiently lowered after 2 h hypoxia in all tissues, but were higher compared with controls after longer hypoxic exposure and recovery. Hypoxia decreased protein thiol content in the liver and muscle that return to control levels during recovery. Experimental conditions affected enzyme activities in a different manner. Superoxide dismutase activity rose two-fold in the liver of hypoxic fish, and a similar tendency was seen in muscle glutathione-S-transferase. Activities of other enzymes were decreased or unchanged during hypoxia and elevated in some cases during normoxic recovery. Taken together, these data show that hypoxia resulted in the development of oxidative stress and a compensatory changes of antioxidant enzymes in the tissues.     

Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver

Dapsone (DDS) is currently used in the treatment of leprosy, malaria and in infections with Pneumocystis jirovecii and Toxoplasma gondii in AIDS patients. Adverse effects of DDS involve methemoglobinemia and hemolysis and, to a lower extent, liver damage, though the mechanism is poorly characterized. We evaluated the effect of DDS administration to male and female rats (30 mg/kg body wt, twice a day, for 4 days) on liver oxidative stress through assessment of biliary output and liver content of reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and expression/activities of the main antioxidant enzymes glutathione peroxidase, superoxide dismutase, catalase and glutathione S-transferase. The influence of DDS treatment on expression/activity of the main DDS phase-II-metabolizing system, UDP-glucuronosyltransferase (UGT), was additionally evaluated. The involvement of dapsone hydroxylamine (DDS-NHOH) generation in these processes was estimated by comparing the data in male and female rats since N-hydroxylation of DDS mainly occurs in males. Our studies revealed an increase in the GSSG/GSH biliary output ratio, a sensitive indicator of oxidative stress, and in lipid peroxidation, in male but not in female rats treated with DDS. The activity of all antioxidant enzymes was significantly impaired by DDS treatment also in male rats, whereas UGT activity was not affected in any sex. Taken together, the evidence indicates that DDS induces oxidative stress in rat liver and that N-hydroxylation of DDS was the likely mediator. Impairment in the activity of enzymatic antioxidant systems, also associated with DDS-NHOH formation, constituted a key aggravating factor.     

Heat shock induces oxidative stress in rotan Perccottus glenii tissues

The effects of temperature transition from 19 to 32 °C on oxidative stress indices and activities of the main antioxidant enzymes were investigated in the rotan, Perccottus glenii. Levels of lipid peroxides (LOOH), thiobarbituric acid-reactive substances (TBARS), low- (L-SH) and high-molecular mass (H-SH) thiols and activities of superoxide dismutase (SOD) and catalase were measured in rotan brain, liver and muscle over 1–12 h of high-temperature exposure followed by 3 or 24 h lower (19 °C) temperature recovery. Heat shock exposure during 1 h transiently increased 1.5–3.2-fold LOOH levels in rotan tissues with subsequent suppression of their content; however, 12 h exposure again increased LOOH levels in the brain. TBARS content were elevated by 2–3-fold during the entire heat shock exposure in the brain and liver. Levels of both products of lipid peroxidation were generally near control values during return to 19 °C. L-SH content was lowered during heat shock exposure in the brain, transiently increased after 6 h in the liver and almost disappeared after longer treatment in the muscle. Liver H-SH content slightly decreased under heat shock exposure, but was elevated after 6 h in the brain and muscle. In the latter case, L-SH level was below control values during recovery. SOD activities increased 2-fold in the liver after 6–12 h heat shock. Liver catalase activities decreased at the same conditions. Generally, a quick response to suppression of lipid peroxidation and possible involvement of its products in the up-regulation of antioxidant enzymes seem to be key adaptations to high temperature.     

Cigarette smoke extract induces oxidative stress and apoptosis in human lung fibroblasts

Cigarette smoke is a mixture of chemicals having direct and/or indirect toxic effects on different lung cells. We investigated the effect of cigarette smoke on human lung fibroblasts (HFL-1) oxidation and apoptosis. Cells were exposed to various concentrations (1, 5, and 10%) of cigarette smoke extract (CSE) for 3 h, and oxidative stress and apoptosis were assessed by fluorescence-activated cell sorting and confocal laser fluorescence microscopy. Both oxidative stress and apoptosis exhibited a dose-response relationship with CSE concentrations. Lung fibroblasts also showed marked DNA fragmentation at the Comet assay after exposure to 10% CSE. Coincubation of HLF-1 cells with N-acetylcysteine (1 mM) during CSE exposure significantly reduced oxidative stress, apoptosis, and DNA fragmentation, whereas preincubation (3 h) with the glutathione-depleting agent buthionine sulfoximine (125 microM) produced a significant increase of oxidative stress. Cigarette smoke is a potent source of oxidative stress, DNA damage, and apoptosis for HFL-1 cells, and we speculate that this could contribute to the development of pulmonary emphysema in the lungs of smokers.     

Proliferation and apoptosis in a neuroblastoma cell line exposed to 900 MHz modulated radiofrequency field

The aim of this study was to examine whether a modulated radiofrequency of the type used in cellular phone communications at a specific absorption rate (SAR) higher than International Commission on Non-ionizing Radiation Protection (ICNIRP) reference level for occupational exposure, could elicit alterations on proliferation, differentiation, and apoptosis processes in a neuroblastoma cell line. The cell line was exposed for 24, 48, and 72 h to 900 MHz radiofrequency and proliferation and differentiation were tested by WST-I assay and by a molecular analysis of specific markers, two oncogenes and a cytoskeleton protein, in exponential growth phase and in synchronized cell cultures. Apoptosis was evaluated by caspase activation analysis and by molecular detection of Poly (ADP-ribose) polimerase (PARP) cleavage. Combined exposures to radiofrequency and to the differentiative agent retinoic acid or to the apoptotic inducer camptothecin were carried out to test possible interference between electromagnetic field and chemical agents. Overall our data suggest that 900 MHz radiofrequency exposure up to 72 h does not induce significant alterations in the three principal cell activities in a neuroblastoma cell line.     

Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver

The present study investigated the effects of chronic hyperprolinemia on oxidative and metabolic status in liver and serum of rats. Wistar rats received daily subcutaneous injections of proline from their 6th to 28th day of life. Twelve hours after the last injection the rats were sacrificed and liver and serum were collected. Results showed that hyperprolinemia induced a significant reduction in total antioxidant potential and thiobarbituric acid-reactive substances. The activities of the antioxidant enzymes catalase and superoxide dismutase were significantly increased after chronic proline administration, while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH, sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the liver revealed that proline treatment induced changes of the hepatic microarchitecture and increased the number of inflammatory cells and the glycogen content. Biochemical determination also demonstrated an increase in glycogen concentration, as well as a higher synthesis of glycogen in liver of hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an increase on glucose oxidation and a decrease on lipid synthesis from glucose. However, hepatic lipid content and serum glucose levels were not changed. Proline administration did not alter the aminotransferases activities and serum markers of hepatic injury. Our findings suggest that hyperprolinemia alters the liver homeostasis possibly by induction of a mild degree of oxidative stress and metabolic changes. The hepatic alterations caused by proline probably do not implicate in substantial hepatic tissue damage, but rather demonstrate a process of adaptation of this tissue to oxidative stress. However, the biological significance of these findings requires additional investigation.