Lower Superoxide Dismutase Levels Research Articles

P-844: Relationship between seminal viscosity and oxidative stress in infertile men

P-844: Relationship between seminal viscosity and oxidative stress in infertile men

P-848: Relationship between Ilex paraguariensis (Chimarrão) consumption and seminal antioxidants levels in infertile men

The controlled generation of reactive oxygen species (ROS) in spermatozoa is associated with normal physiological functions. Uncontrolled and excessive production of ROS however, appears to have a significant role as one of the major factors leading to an infertile status. Superoxide dismutase (SOD) and catalase are important antioxidant enzymes that can quench excessive free radicals such as: superoxide anion and hydrogen peroxide respectively. One of the most commonly used beverages in South America, especially in countries such as Argentine, Uruguay, Paraguay and South of Brazil is called “Mate” or “Chimarrão”. It is based on the herb named “Ilex Paraguariensis” which contains caffeine. The objective of our study was to evaluate and compare the seminal antioxidant enzymatic activity (SOD and Catalase levels) among fertile and infertile men who consume “Mate”. Case control study The study was approved by the Institutional Review Board and the patients provide their informed consent. The study included twenty-one fertile donors who did not consume “Mate” regularly and 112 infertile patients, who regularly consumed “Mate”. Patients were asked about the amount (mL) of “Mate’ they drink daily. Semen samples were obtained by masturbation after at least 48 hours of abstinence. Samples were collected into sterile containers and allowed to liquefy at 37°C for 30 minutes and analyzed for viscosity (normal, moderate, high), sperm concentration, percent motility, and morphology according to WHO criteria. Superoxide Dismutase and Catalase levels were determined with a spectrophotometer. The activity of the SOD was based on the adrenocromo concentration, resulting from the adrenaline oxidation by the radical superoxide. Catalase activity was determined by the velocity of hydrogen peroxide consumed. Compared to fertile donors the infertile men had significantly lower levels of SOD (13.2 ± 5.3 and 41.03 ± 7.5; P = 0.01) and catalase (14.11 ± 5.4 and 36.03 ± 5.36; P = 0.02). A significant correlation between catalase and SOD was observed (r = 0.316, P = 0.001). Sperm morphology by Tygerberg criteria was significantly correlated with the levels of SOD (r = 0.457, P = 0.001) and catalase (r = 0.393, P = 0.001). Sperm motility was correlated with Catalase (r = 0.276, P = 0.03). “Mate” intake was correlated with SOD levels (r = 0.268, P = 0.04), and Catalase levels (r = 0.311, P = 0.01). Patients who drank more than 300 mL of “Mate” per day had higher SOD (15.6 ± 3.8) and Catalase (16.1 ± 2.1) compared to men who did not drink ‘Mate” (SOD = 11.4 ± 3.8; P = 0.042) (Catalase = 12.1 ± 2.5; P = 0.037). Consumption of the herbal beverage “Mate” was correlated with improved sperm motility and morphology in patients evaluated for infertility. This improvement in semen parameters appears to be mediated by increased seminal antioxidant activity in these men.

Antioxidant and Lipid Peroxidation Levels in Fertile and Infertile Men

The generation of reactive oxygen species (ROS) in the male reproductive tract has become a real concern due to its potential toxic effects at high levels on sperm quality and function. Human spermatozoa are rich in polyunsaturated fatty acids and are therefore susceptible to ROS attack. Among the well known biological antioxidants, superoxide dismutase (SOD), catalase, and glutathione peroxidase/reductase system have a significant role in protecting the sperm against peroxidative damage The objective of our study was to evaluate the seminal antioxidant enzymatic activity (SOD and catalase) and lipid peroxidation levels among fertile and infertile men. Retrospective study at a tertiary care institution. The Institutional Review Board approved this study. Ten fertile donors and 112 infertile patients were included in the study. Semen analysis was performed according to the World Health Organization guidelines and sperm morphology according to Tygerberg strict criteria. Lipid peroxidation levels were estimated by thiobarbituric acid assay. Superoxide dismutase and catalase levels were determined with a spectrophotometer. Significantly lower levels of SOD (14.67 ± 12.27 vs 38.03 ± 21.65) and catalase (14.87 ± 16.95 vs 34.03 ± 20.65) were seen in infertile patients compared to fertile donors (P <0.0001). A significant correlation was seen between catalase and SOD levels (r = 0.461, P = 0.0001). Lipid peroxidation levels were inversely correlated with SOD (r = -0267, P = 0.035). Superoxide dismutase was significantly correlated with sperm concentration (r = 0.204, P = 0.034) and negatively with leukocytospermia (r = -0.228, P = 0.021). Low antioxidant enzyme and high lipid peroxidation levels are associated with male infertility. Oxidative stress precipitates a range of pathologies that are thought to affect the male reproductive system. Determining the levels and the sources of excessive ROS production in human semen and precise evaluation of the scavenger system are useful tools in developing therapeutic strategies for male infertility.

Regular Coffee Intake is Related to Increased Sperm Motility and Antioxidant Levels in Infertile Men

Regular Coffee Intake is Related to Increased Sperm Motility and Antioxidant Levels in Infertile Men

1516: Relationship between Cigarette Smoking and the Levels of Antioxidants and Leukocytes in Infertile Men: A Prospective Study

Introduction and Objective: Cigarette smoke is a known somatic cell mutagen and carcinogen and it is known to adversely affect male reproductive health. Even though studies have shown the harmful effets of smoking on sperm quality, a handful of studies have found no association between smoking and sperm function or sperm nuclear DNA damage. Superoxide dismutase (SOD) and catalase are important antioxidant enzymes that can quench excess free radicals such as: superoxide anion and hydrogen peroxide respectively. The objective of our study was to evaluate and correlate the seminal antioxidant enzymatic activity (SOD and catalase levels) among fertile and infertile men who are cigarette smokers. Methods: The Institutional Review Board approved this study. Ten fertile donors and 112 infertile patients were included in the study. Semen analysis was performed according to the World Health Organization guidelines and sperm morphology according to Kruger strict criteria. Superoxide dismutase and catalase levels were determined with a spectrophotometer. Results: A significant difference was noted in the number of cigarettes smoked/day between infertile (4.8 ± 0.9) and fertile men (1.5 ± 0.5; p = 0.03). Significantly lower levels of SOD (14.67 ± 12.27 and 38.03 ±21.65) and catalase (14.87 ± 16.95 and 34.03 ± 20.65) were seen in infertile patients compared to fertile donors (P <0.0001). A significant correlation between catalase and SOD was observed (r = 0.461, P = 0.0001). Superoxide dismutase was significantly correlated with sperm concentration (r = 0.204, P = 0.034) and negatively correlated with leukocytospermia (r = -0.228, P = 0.021). Cigarette smoking was inversely correlated with SOD levels (r = -0.251, P = 0.01), but not with catalase levels (r = -0.147, P = 0.130). Conclusions: Decreased antioxidant enzyme levels are associated with male infertility. The detrimental effects of cigarette smoking on sperm motility and antioxidant levels (negative correlation with SOD) may be a possible reason for infertility in men who smoke cigarettes. As low antioxidant levels are linked to decreased fertility, physicians should advise infertile patients who smoke cigarettes to quit smoking. Author Disclosure Block: E.B. Pasqualotto, None; F.M. Umezu, None; A. Agarwal, None; M. Salvador, None; F.F. Pasqualotto, None.

Superoxide Dismutase Inactivation in Pathophysiology of Asthmatic Airway Remodeling and Reactivity

Airway hyperresponsiveness and remodeling are defining features of asthma. We hypothesized that impaired superoxide dismutase (SOD) antioxidant defense is a primary event in the pathophysiology of hyperresponsiveness and remodeling that induces apoptosis and shedding of airway epithelial cells. Mechanisms leading to apoptosis were studied in vivo and in vitro. Asthmatic lungs had increased apoptotic epithelial cells compared to controls as determined by terminal dUTP nick-end labeling-positive cells. Apoptosis was confirmed by the finding that caspase-9 and -3 and poly (ADP-ribose) polymerase were cleaved. On the basis that SOD inactivation triggers cell death and low SOD levels occur in asthma, we tested whether SOD inactivation plays a role in airway epithelial cell death. SOD inhibition increased cell death and cleavage/activation of caspases in bronchial epithelial cells in vitro. Furthermore, oxidation and nitration of MnSOD were identified in the asthmatic airway, correlating with physiological parameters of asthma severity. These findings link oxidative and nitrative stress to loss of SOD activity and downstream events that typify asthma, including apoptosis and shedding of the airway epithelium and hyperresponsiveness.

The activities of antioxidant enzymes in response to oxidative stresses and hormones in paraquat-tolerant Rehmannia glutinosa plants.

All members of R. glutinosa show the unique characteristic of intrinsic tolerance to paraquat (PQ). Antioxidant enzymes have been proposed to be the primary mechanism of PQ resistance in several plant species. Therefore, the antioxidant enzyme systems of R. glutinosa were evaluated by comparatively analyzing cellular antioxidant enzyme levels, and their responses of oxidative stresses and hormones. The levels of ascorbate peroxidase (APX), glutathione reductase (GR), non-specific peroxidase (POX), and superoxide dismutase (SOD) were 7.3-, 4.9-, 2.7- and 1.6-fold higher in PQ-tolerant R. glutinosa than in PQ-susceptible soybeans. However, the activity of catalase (CAT) was about 12-fold higher in the soybeans. The activities of antioxidant enzymes reduced after PQ treatment in the two species, with the exception of POX and SOD in R. glutinosa, which increased by about 40 %. Interestingly, the activities of APX, SOD and POX in R. glutinosa, relative to those in soybeans, were further increased by 49, 67 and 93 % after PQ treatment. The considerably higher intrinsic levels, and increases in the relative activities of antioxidant enzymes in R. glutinosa under oxidative stress support the possible role of these enzymes in the PQ tolerance of R. glutinosa. However, the relatively lower levels of SOD versus PQ tolerance, and the mixed responses of antioxidant enzymes to stresses and hormones, suggest a possible alternative mechanism(s) for PQ tolerance in R. glutinosa.

Evidence of oxidative stress in the circulation of ovarian cancer patients

Background: Ovarian cancer is the leading cause of death due to gynecological malignancies among women. The extent of free radical induced oxidative stress can be exacerbated by the decreased efficiency of antioxidant mechanisms. The present study was conducted to investigate the extent of oxidative stress and the levels of antioxidants in the circulation of ovarian cancer patients. Methods: Plasma thiobarbituric acid reactive substances (TBARS) and conjugated dienes (CD) and the levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT), vitamin C and vitamin E were estimated in the circulation of 30 ovarian cancer patients and an equal number of age-matched normal subjects as control. Results: Significantly increased concentrations of plasma TBARS and CD and significantly lowered levels of SOD, CAT, vitamin C and vitamin E were observed in ovarian cancer patients as compared with normal subjects. Conclusion: The low levels of SOD, CAT, vitamin C and vitamin E in the plasma of ovarian cancer patients may be due to their increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells. Increased levels of lipid peroxidation may be due to excessive oxidative stress caused by incessant ovulation or epithelial inflammation.

Modulation of cortical nitric oxide synthase, glutamate, and redox state by nifedipine and taurine in PTZ-kindled mice.

Correlation between pentylenetetrazol (PTZ)-induced kindling and the cortical nitric oxide synthase (NOS), intracellular calcium [Ca2+]i, glutamate, and free radicals was studied in mice, as well as the modulatory action of nifedipine and taurine on these parameters. Male Swiss albino mice were used. Mice in one group received a single convulsive dose of PTZ (50 mg/kg, i.p), and were killed 24 h later. To induce kindling, PTZ was injected in a subconvulsive dose (40 mg/kg, i.p.) every other day for 3 weeks. One kindled group was used as control, whereas two other groups were injected 30 min before PTZ with either nifedipine (30 mg/kg, i.p) or taurine (100 mg/kg, i.p). All three kindled groups were killed 24 h after the last injection. Compared with normal control group, PTZ-kindled mice had significantly higher levels of [Ca2+]i, malonaldehyde (MDA), NOS, and lactate dehydrogenase (LDH) but had lower levels of superoxide dismutase (SOD) and reduced glutathione (GSH). Acute seizures of the same intensity did not induce these alterations, indicating their link to the kindling phenomenon and not to seizure activity. The effect of taurine, known as an antioxidant, was more pronounced than that of the Ca2+-channel blocker, nifedipine. The first drug reversed the PTZ-kindled action on [Ca2+]i, NOS, LDH, GSH, and SOD, whereas nifedipine restored only LDH and GSH levels. However, both drugs did not restore the elevated MDA level. This study suggests that free radicals, as well as NOS, are implicated in PTZ-induced kindling, and that antioxidants could play a role in controlling the accompanying changes.

Visualizing Superoxide Production in Normal and Diabetic Rat Islets of Langerhans

Oxygen free radicals have been implicated in beta-cell dysfunction and apoptosis associated with type 1 and type 2 diabetes mellitus. The roles of free radicals in diabetes have thus far been defined indirectly by monitoring oxidative tissue damage and the effects of antioxidants, free radical scavengers, and overexpression of superoxide dismutase. We employed the superoxide-mediated oxidation of hydroethidine to ethidium to dynamically and directly assess the relative rates of mitochondrial superoxide anion generation in isolated islets in response to glucose stimulation. Superoxide content of isolated islets increased in response to glucose stimulation. We next compared the oxyradical levels in Zucker lean control and Zucker diabetic fatty rat islets by digital imaging microfluorometry. The superoxide content of Zucker diabetic fatty islets was significantly higher than Zucker lean control islets under resting conditions, relatively insensitive to elevated glucose concentrations, and correlated temporally with a decrease in glucose-induced hyperpolarization of the mitochondrial membrane. Importantly, superoxide levels were elevated in islets from young, pre-diabetic Zucker diabetic fatty animals. Overproduction of superoxide was associated with perturbed mitochondrial morphology and may contribute to abnormal glucose signaling found in the Zucker diabetic fatty model of type 2 diabetes mellitus.

Retinal endothelial cells are more susceptible to oxidative stress and increased permeability than brain-derived endothelial cells

Increased vascular permeability and oxidative stress are important in diabetic retinopathy. Because the cerebral microcirculation is much less affected in diabetes, our objectives are to compare: (1) glutathione peroxidase activity, (2) superoxide dismutase levels, (3) superoxide production, and (4) junctional protein (ZO-1) levels between retinal and brain-derived endothelial cells. Bovine brain and retinal endothelial cell cultures are incubated in medium containing either mM or 30 mM glucose for 5 days. Superoxide is measured in the medium and endothelial cells are then lysed and analyzed for glutathione peroxidase activity as well as levels of superoxide dismustase and ZO-1. The results demonstrate that, compared to brain-derived endothelial cells, retinal endothelial cells release high levels of superoxide, have less glutathione peroxidase activity and lower levels of superoxide dismutase, and ZO-1. Also, unlike brain-derived endothelial cells where ZO-1 levels increased in response to glucose, in retinal endothelial cells, ZO-1 levels are unaffected by glucose. These findings suggest that greater oxidative stress and lower junctional protein levels in retinal endothelial cells may contribute to blood/retinal barrier dysfunction in diabetic retinopathy.

Circulating lipid peroxidation and antioxidant status in cervical cancer patients: a case-control study

Objectives: The present case-control study was conducted to investigate the status of circulating lipid peroxidation and the enzymic and nonenzymic antioxidants of cervical cancer patients. Design and methods: Plasma thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and the levels of antioxidants such as reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), vitamin C and vitamin E were estimated in circulation of thirty patients and an equal number of age matched normal subjects as control. Results: Significantly elevated levels of plasma TBARS and CD and significantly lowered levels of GSH, GPx, GST, SOD vitamin C and vitamin E were observed in cervical cancer patients as compared to controls. Our study reveals increased lipid peroxidation and possible breakdown of antioxidant status in patients with cervical carcinoma. Conclusion: These results indicate that low levels of GSH, GPx, GST, SOD, vitamin E and vitamin C in the circulation of cervical cancer patients may be due to their increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells. Malnutrition may also be a significant cause for the increased prevalence of cervical cancer in women with a low socioeconomic status.

Myocardial antioxidant and oxidative stress changes due to sex hormones.

The purpose of the present study was to examine myocardial antioxidant and oxidative stress changes in male and female rats in the presence of physiological sex hormone concentrations and after castration. Twenty-four 9-week-old Wistar rats were divided into four groups of 6 animals each: 1) sham-operated females, 2) castrated females, 3) sham-operated males, and 4) castrated males. When testosterone and estrogen levels were measured by radioimmunoassay, significant differences were observed between the castrated and control groups (both males and females), demonstrating the success of castration. Progesterone and catalase levels did not change in any group. Control male rats had higher levels of glutathione peroxidase (50%) and lower levels of superoxide dismutase (SOD, 14%) than females. Control females presented increased levels of SOD as compared to the other groups. After castration, SOD activity decreased by 29% in the female group and by 14% in the male group as compared to their respective controls. Lipid peroxidation (LPO) was assessed to evaluate oxidative damage to cardiac membranes by two different methods, i.e., TBARS and chemiluminescence. LPO was higher in male controls compared to female controls when evaluated by both methods, TBARS (360%) and chemiluminescence (46%). Castration induced a 200% increase in myocardial damage in females as determined by TBARS and a 20% increase as determined by chemiluminescence. In males, castration did not change LPO levels. These data suggest that estrogen may have an antioxidant role in heart muscle, while testosterone does not.

Effect of Cu/Zn-superoxide dismutase from the fungal strain Humicola lutea 103 on antioxidant defense of Graffi tumor-bearing hamsters.

A novel Cu/Zn-containing superoxide dismutase (SOD) was isolated from the fungal strain Humicola lutea 103. Previously, a protective effect of this enzyme (HLSOD) against tumor growth and also superoxide production in Graffi tumor-bearing hamsters (TBH) were established. The aim of the present study was to investigate the effect of HLSOD on the activity of endogenous SOD and catalase in the cells from TBH during tumor progression. Our results point out that transplantation of Graffi tumor causes a significant decrease in SOD activity in the cells from liver of the hosts (from 35 to 59% compared to the control). In the tumor cells relatively low levels of SOD (about 7 U mg protein(-1)) were found, and Cu/ZnSOD was the main isoenzyme in total SOD activity. Tumor growth resulted in a reduction of catalase activity, which correlated with the process of tumor progression. A single dose (65 U) treatment with HLSOD caused an increase in endogenous SOD and catalase activity in healthy animals and resulted in restoration of the antioxidant ability in liver cells of the hosts at the early stage of tumor progression. The results show the possible participation of HLSOD in the host oxidant-antioxidant balance, which is probably one of the factors of its immunoprotective action established earlier.

Impaired Antioxidant Defense System of Colonic Tissue and Cancer Development in Dextran Sulfate Sodium-Induced Colitis in Mice

Background. The mechanisms underlying the frequent development of carcinomas associated with ulcerative colitis (UC) are not understood. Cellular antioxidants play a crucial role in protection against neoplastic disease. The purpose of this study is to investigate a critical balance between free radical activity and the antioxidant defense system in carcinogenesis associated with UC, using a model of experimental colitis induced in mice by dextran sulfate sodium (DSS) treatment.Methods. Chronic colitis was induced by feeding the mice for 7 days with 4% DSS, followed by drinking water alone for the subsequent 14 days. Animals were sacrificed after one, two, three, or four cycles of DSS administration. Development of dysplastic epithelium and invasive carcinoma was histologically examined. Lipid peroxide level was estimated by measuring malondialdehyde (MDA) content. Alterations in MDA content and superoxide dismutase (SOD) activity in colonic tissues together with production of serum tumor necrosis factor (TNF)-α were determined.Results. Colonic neoplasms including dysplastic epithelium and invasive carcinoma developed in 28.6 and 25.0% of the animals at the end of the third and fourth cycles, respectively. In accordance with elevation of serum TNF-α level, there was a substantial increase in MDA in the colonic mucosa, while tissue SOD activity tended to be suppressed during the DSS treatment periods. Dysplastic epithelium and invasive carcinoma revealed significantly lower SOD levels compared with colonic colitis, although MDA levels were not statistically different among these colonic diseases.Conclusions. The results obtained in this experimental model suggest that an impaired antioxidant defense system might be critical for cancer development associated with UC.

The effect of oxidizing agents and diabetes mellitus on the human red blood cell membrane potential

Diabetes mellitus is a complex disorder of deranged carbohydrate and lipid metabolism. It may be classified as type 1, type 2, or gestational, all associated with diminished insulin production, secretion, or activity. Any mechanism that leads to hypoinsulinemia results in suppression of enzyme activities related to glycolysis, lipogenesis, and the pentose phosphate pathways while promoting gluconeogenic, glycogenolytic, and lipolytic enzyme activities. Oxidative stress perpetuated by free radical production is vital in the pathogenesis of diabetes. The combination of increased ROS and inflammatory markers results in cellular damage, especially of pancreatic beta cells, along with tissue and end-organ damage. Highly reactive superoxide radicals are routinely produced by cells and detoxified by superoxide dismutase (SOD). Alternatively, low SOD levels and other antioxidant enzymes predispose tissues to pathological damage resulting from oxidative stress. The effectiveness of SOD as an antioxidant makes it useful in treating diabetes by enhancing pancreatic beta cell antioxidant capacity.

Oxidative DNA Damage Induced by Silica in Vivo

Occupational exposure to silica has often been associated with the development of pulmonary fibrosis and, occasionally, lung cancer. Their development may be mediated by oxidant-induced cellular injury, The short- and long-term effects of a single intratracheal instillation of silica in rats (10 mg/200 μl/saline per rat) was assessed by measuring 8-hydroxy-2′-deoxyguanosine (oh8dG) levels in lung tissue and peripheral blood leukocytes. Cell differentials, reduced glutathione (GSH), superoxide dismutase (SOD), lipid peroxide, and total phospholipids in peripheral blood and/or bronchoalveolar lavage fluid (BALF) were also measured, The pulmonary oh8dG level increased approximately 2.24- to 2.86-fold from 1 to 5 days after exposure to silica. It was still elevated 1 and 4 weeks after instillation, but the difference was no longer statistically significant, The oh8dG; levels in peripheral blood leukocytes were never significantly different, but they were generally higher than in the controls, The low SOD levels in the BALF of exposed rats in the early stage and the higher GSH levels in the late stage may represent protective reactions against the generation of oxygen species, A significant increase in oh8dG levels in lung tissue suggested the possible carcinogenicity of silica.

The variation of superoxide dismutase (SOD) and xanthine oxidase (XO) activities in milk using an improved method to quantitate SOD activity

AbstractAn improved method for determination of superoxide dismutase (SOD) in milk has been developed. The interference of endogenously occurring xanthine oxidase (XO) has been subs'antially reduced by addition of an ultrafiltration step, which removed 61 ± 10 (mean ± SD) % of the XO activity. This method was used to determine the SOD activity in milk serum from 15 Swedish Red and White (SRW) cows and 18 Swedish Friesian (SF) cows at various stages of lactation. The XO activity in raw milk was also determined. The milk from these cows had a mean SOD activity of 0.83 ± 1.14 U ml−1 milk serum and a mean XO activity of 49 ± 22 mU ml−1 raw milk (n = 127). A difference between breeds could be noted in XO activity, ie milk from SF cows had significantly (P &lt; 0.05) higher mean XO levels compared with milk from SRW cows, 54 ± 23 mU ml−1 than 44 ± 21 mU ml−1. A significantly increased level of XO activity in milk from SRW cows during the lactation was found. No significant effect of breed or stage of lactation on SOD activity could be detected. Individual cows with high and low milk SOD levels during the entire lactation have been identified.

Platelet Superoxide Dismutase in Migraine and Tension-Type Headache

Superoxide dismutase (SOD) is a radical-scavenging enzyme. We determined Cu, Zn-SOD concentrations and activities in platelets from subjects with migraine and tension-type headaches. Thirty migraine without aura (MWoA) patients, 9 migraine with aura (MWA) patients, and 53 tension-type headache patients were selected for study. Thirty healthy volunteers composed the control group. Concentrations of platelet SOD were determined using enzyme-linked immunosorbent assay techniques. The activity of platelet SOD was determined by measuring reductivity of nitroblue tetrazolium. Low concentrations of platelet SOD were found in patients with MWA and MWoA. Platelet SOD activity decreased in MWA patients but not in patients with MWoA or tension-type headaches. These findings suggest vulnerability to oxidative stress in patients with migraine. It is suggested that low platelet SOD levels may play an important role in the etiology of migraine.

Characteristics of mutagenesis by glyoxal in Salmonella typhimurium: contribution of singlet oxygen

The characteristics of mutagenesis by glyoxal in Salmonella tester strains TA100 and TA104, and particularly a possible role of active oxygen species, were investigated. Glyoxal was converted into a non-mutagenic chemical with glutathione (GSH) by glyoxalase I, and the mutagenic activity was enhanced by the depletion of intracellular GSH. Glyoxal caused the reduction of nitro blie tetrazolium, which was suppressed by the addition of 2,5-diphenylfuran, superoxide dismutase (SOD) and catalase (CAT), scavengers of singlet oxygen ( 1O 2), superoxide radical ( O 2 ̇ − ) and hydrogen peroxide (H 2O 2), respectively. However, only the 1O 2 scavenger almost completely suppressed the mutagenic activity of glyoxal. Mutagenicity assays using strains pretreated with N, N-diethydithiocarbamate of a SOD inhibitor and strains with low levels of SOD and CAT indicated that the mutagenesis by glyoxal was independent of intracellular levels of SOD and CAT, though glyoxal itself repressed them. Therefore, all the results suggest that 1O 2 formed from glyoxal is related to its mutagenesis, but that neither O 2 ̇ − nor H 2O 2 is intracellularly predominantly related to it. The action of glyoxal against SOD and CAT, and the formation of glyoxal adducts with amino acids as their components are also discussed.