Antioxidative enzymes in human nasal mucosa after exposure to ozone. Possible role of GSTM1 deficiency

OBJECTIVE AND DESIGN: Epithelial antioxidative enzymes (AOEs) are thought to be a first line of defense against reactive oxygen species as they are upregulated after exposure to ozone according to animal studies. We analysed the activities of the AOEs catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD) and glutathione-S-transferase (GST) in a tissue culture of human nasal mucosa and analysed the influence of GSTM1 polymorphism on AOE regulation. METHODS: Tissue biopsies of 20 subjects were incubated for 24 h with and without 120 ppb ozone. Activities were assayed to determine what enzymatic changes had taken place, both overall and in regard to GSTM1 status. RESULTS: Activities for GPX (p = 0.272) and SOD (p = 0.291) were found increased after ozone exposure. GSTM1-deficient patients showed a significantly enhanced upregulation of SOD activity (p = 0.011) compared to GSTM1 carriers. CONCLUSION: Our findings suggest that GSTM1-deficiency has an impact on AOE-regulation after ozone exposure.     

Influence of sex and age on the activity of antioxidant enzymes of polymorphonuclear leukocytes in healthy subjects

In this study, the main antioxidant enzymes (AOE) of glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) were identified, and the influence of sex and age in healthy human polymorphonuclear leukocytes (PMNL) was determined. The SOD, GPX, CAT and MPO activities were investigated in intestinal parasite negative human PMNL from 109 healthy subjects aged from 6 to 70 years (55 males and 54 females) using simple and sensitive enzyme assays. Blood cells, such as eosinophils, platelets, neutrophils, monocytes, and macrophages also synthesize antioxidant enzymes (AOE). They constitute an important proportion and are also the major participants in a number of pathological conditions that suggest the involvement of AOE. A linear effect of age on SOD activity (p < 0.05) both in males and females was found. A similar effect with GPX activity (p < 0.05) was observed in males only. This showed that the activities of all these enzymes increase with age. In addition, SOD activity was significantly higher in females than males between the age of 19 and 70 years (p < 0.001). This analysis also showed that there is a negative correlation between the CAT-GPX (p < 0.05) activities and positive correlations between MPO-GPX (p < 0.05) activities only in females. No correlation among the other enzyme activities was found in either sex group. This study showed the activities of antioxidant enzyme activities and the correlations of these enyzmes activities with each other in healthy human PMNLs were age- and sex-dependent. This information may assisit in understanding the importance of antioxidant enzymes in the physiological and pathological conditions associated with PMNL.     

Antioxidant parameters and ageing in some animal species

Connection between ageing and some tissue antioxidant parameters have been studied in four experiments on different animal species. Prenatal studies on the developing chick embryos showed discrepancies between the lipid-rich liver and brain antioxidant defence. In the liver, high levels of reduced glutathione (GSH), vitamins A and E and high activities of the antioxidant enzymes glutathione peroxidase (GPX) and superoxide dismutase (SOD) were found whereas brain expressed a high vitamin C concentration. In newborn healthy calves during the first two days of life, atmospheric oxygen tension did not cause either increased lipid peroxidation as reflected in a high malondialdehyde (MDA) level or any changes in GSII, GPX, SOD and catalase (CAT) activities in red blood cells (RBC). Plasma vitamin E and carotene concentrations also did not change. In growing healthy calves during two months after birth increasing MDA, decreasing GSH, GPX and CAT are leading features, whereas plasma vitamin E and carotene concentrations significantly increased. In young (1-year-old) and old (9-year-old) dogs RBC results showed significant differences with the highest MDA and lowest GSH levels in the old males. Activity of GPX and SOD was higher in old dogs than in the young ones, especially in the females.     

Altered Activities of Antioxidant Enzymes in Patients with Metabolic Syndrome

ObjectiveIn the pathogenesis of the metabolic syndrome (MetS), an increase of oxidative stress could play an important role which is closely linked with insulin resistance, endothelial dysfunction, and chronic inflammation. The aim of our study was to assess several parameters of the antioxidant status in MetS.Methods40 subjects with MetS and 40 age- and sex-matched volunteers without MetS were examined for activities of superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), paraoxonase1 (PON1), concentrations of reduced glutathione (GSH), and conjugated dienes in low-density lipoprotein (CD-LDL).ResultsSubjects with MetS had higher activities of CuZnSOD (p ℋ 0.05) and GR (p ℋ 0.001), higher concentrations of CD-LDL (p ℋ 0.001), lower activities of CAT (p ℋ 0.05) and PON1 (p ℋ 0.05), and lower concentrations of GSH (p ℋ 0.05), as compared with controls. Activity of GPX1 was not significantly changed.ConclusionsOur results implicated an increased oxidative stress in MetS and a decreased antioxidative defense that correlated with some laboratory (triglycerides, high-density lipoprotein cholesterol (HDL-C)) and clinical (waist circumference, blood pressure) components of MetS.Key Words: Metabolic syndrome, Antioxidant enzymes, Reduced glutathione, Conjugated dienes     

Effects of acute exercise on lung antioxidant enzymes in young and old rats

The lung could be the target organ to cellular damage, since it is directly exposed to high concentrations of oxygen. Acute exercise and age would be an added challenge to the lung, and therefore, we investigated alterations of major lung antioxidant enzymes (manganese-superoxide dismutase, Mn-SOD; copper-zinc-SOD, Cu-Zn-SOD; glutathione peroxidase, GPX; catalase, CAT) activities and mRNA expressions in young (4 months old) and old (26 months old) male Wistar rats with exercise. Thioredoxin reductase (TrxR) activity was also investigated. Mn-SOD and Cu-Zn-SOD increased with age, but age did not affect GPX, CAT, or TrxR activity. Acute exercise in young animals increased the activities of Mn-SOD, Cu-Zn-SOD, and CAT. In contrast, only Mn-SOD increased significantly in the old animals. The mRNA expressions of Mn-SOD, Cu-Zn-SOD and GPX were not altered with age, while CAT mRNA expression decreased with age. Acute exercise had no significant effect on any of the antioxidant enzyme mRNA expression. Moreover, reactive carbonyl derivative increased with age, but no significant changes were detected after acute exercise in either group. In summary, antioxidant enzymes responsible for the removal of hydrogen peroxide were unable to increase their enzyme activities in the old animals with exercise.     

Glutathione peroxidase and reductase activities in the aging mouse

Previous results from this laboratory demonstrated that glutathione concentrations decrease in aging mouse tissues. In this investigation glutathione (GSH) peroxidase and glutathione (GSSG) reductase activities were measured in tissues of standardized aging mice. Methods were validated for the quantitative determination of both enzymes in liver, kidney and heart tissues. GSH peroxidase activities were 27-53% lower in liver, kidney and heart of very old (36 months) mice compared to mature (10 months) mice (P less than 0.01). The same aging decreases were found with either hydrogen peroxide or cumene hydroperoxide as substrate. In a similar way GSSG reductase activities in liver and kidney were 25-28% lower in the old versus mature mice (P less than 0.01), but heart levels were unchanged. Further the lower GSSG reductase levels were unaffected by FAD supplementation in vitro. The changes in specific activity for both enzymes were not due to changes in organ weights and total protein contents, which were constant from 10 to 36 months of age. These decreases in GSH peroxidase and GSSG reductase do not account for the lower GSH levels in aging. Of special importance, however, is that these decreases indicate that detoxification via glutathione peroxidase and glutathione reductase could be impaired in senescence.     

Relationship between NADP-specific isocitrate dehydrogenase and glutathione peroxidase in aging rat skeletal muscle

The glutathione peroxidase (GPX) system detoxifies hydroperoxides in cells and uses NADPH to regenerate reduced glutathione. Enzymatic sources of NADPH in skeletal muscle include NADP-specific isocitrate dehydrogenase (ICDP), glucose-6-phosphate dehydrogenase (G6PD), and malic enzyme (ME). Our purpose was to explore the relationship in skeletal muscle between GPX and ICDP along with other NADPH-generating enzymes as a function of progressive age and muscle fiber-type. Soleus (SOL), red gastrocnemius (RG), and white gastrocnemius (WG) muscles were extracted from Fischer-344 rats of three different ages: 4 months old (Y); 18 months old (M); and 24 months old (O). Assays were conducted to determine activities of GPX, ICDP, G6PD, and ME along with levels of lipid hydroperoxides. GPX activities were significantly greater in RG and WG of old rats than in younger. ICDP activities were higher in the WG of old and middle aged rats when compared to young adults. GPX and ICDP activities exhibited similar differences among the muscles tested (SOL>RG>WG). In contrast, G6PD and ME activities were not significantly different across muscles. G6PD activities increased in RG with age, but were well over an order of magnitude lower than ICDP in all muscles. ME activities were universally lower than ICDP in all muscles, and decreased with old age in the WG and RG. Lipid hydroperoxides were significantly higher with aging in RG. Significant correlations were found between GPX and ICDP in all muscles. Stepwise regression resulted in a model (R(2)=0.82) that included ICDP and ME in predicting GPX. In summary, these data are consistent with the hypotheses that ICDP is higher in more oxidative fibers, inducible with aging, and most closely associated with the glutathione peroxidase system in skeletal muscle.     

Effect of age on the expression of antioxidant enzymes in male Fischer F344 rats

Age-related changes in the activities of superoxide dismutase, catalase, and glutathione peroxidase were determined in brain, heart, hepatocytes, intestinal mucosa, and kidney from male Fischer F344 rats. Superoxide dismutase activity decreased significantly with age in all five tissues studied. The activity of catalase decreased with age in brain, hepatocytes, and kidney while glutathione peroxidase activity decreased significantly with age only in intestinal mucosa and kidney. The relative levels of superoxide dismutase, catalase, and glutathione peroxidase mRNA were measured in brain, hepatocytes, and kidney. An age-related decrease in SOD and catalase mRNA was observed for brain, hepatocytes, and kidney. GPX mRNA levels decreased with age in hepatocytes and kidney but did not change with age in brain. In general, the age-related changes in the activities of SOD, catalase, and GPX were paralleled by a similar change in the relative level of the mRNAs coding for these enzymes.     

Linkage of conidial longevity determinant genes in Neurospora crassa

The longevity of conidia of Neurospora crassa was previously defined as their ability to grow after aging in a constant environment. The heritable median lifespan of the wild type is 22 days. Heritable mutants with lifespans of 5-7 days were previously selected. The pleiotropic colony phenotype of the mutants greatly facilitates genetical analysis of their inheritance. Twenty-eight mutants were mapped by recombinational analysis. All but one were located at genes on one arm of the seven chromosomes, linkage group IR; the exception was at the terminus of linkage group VIR. Sixteen of the 17 genes on IR are collectively called the age-1 complex. The average and standard deviation of the distance of 13 intervals between adjacent genes in the complex was 4.9 +/- 1.1 map units; hence they appear to be spatially reiterated. Other observations indicate that the genes are also functionally redundant.     

The effects of di(2‐ethylhexyl)phthalate on rat liver in relation to selenium status

This study was performed to determine the hepatotoxicity of di(2‐ethylhexyl)phthalate (DEHP) in relation to selenium status. In 3‐week‐old Sprague‐Dawley rats, selenium deficiency was induced by a ≤0.05 selenium mg/kg. A selenium supplementation group was given 1 mg selenium/kg diet for 5 weeks. Di(2‐ethylhexyl)phthalate‐treated groups received 1000 mg/kg dose by gavage during the last 10 days of the experiment. Histopathology, peroxisome proliferation, catalase (CAT) immunoreactivity and activity and apoptosis were assessed. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR1)], superoxide dismutase (SOD), and glutathione S‐transferase (GST); aminotransferase, total glutathione (tGSH), and lipid peroxidation (LP) levels were measured. Di(2‐ethylhexyl)phthalate caused cellular disorganization while necrosis and inflammatory cell infiltration were observed in Se‐deficient DEHP group (DEHP/SeD). Catalase activity and immunoreactivity were increased in all DEHP‐treated groups. Glutathione peroxidase 1 and GPx4 activities decreased significantly in DEHP and DEHP/SeD groups, while GST activities decreased in all DEHP‐exposed groups. Thioredoxin reductase activity increased in DEHP and DEHP/SeS, while total SOD activities increased in all DEHP‐treated groups. Lipid peroxidation levels increased significantly in SeD (26%), DEHP (38%) and DEHP/SeD (71%) groups. Selenium supplementation partially ameliorated DEHP‐induced hepatotoxicity; while in DEHP/SeD group, drastic changes in hepatic histopathology and oxidative stress parameters were observed.     

Relationship between oxidative stress in muscle tissue and weight-lifting-induced muscle damage

We examined whether oxidative stress-induced muscle damage occurs during weight-lifting exercise using the rat model. Male Wistar rats were subjected to a single exhaustive session of weight-lifting exercise, and dynamics of blood volume and hemoglobin levels in the exercising muscle were monitored by near-infrared spectroscopy. Total muscle damage was evaluated by the efflux of serum creatine kinase (CK) and uptake of [³H]thymidine. The production of reactive oxygen species (ROS) in the muscle was estimated by serial changes in total superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) activities (established indirect markers). Immunohistochemical detection of GPX was also performed. A relatively anoxic state occurred repeatedly after every exercise set in exercising muscle following rapid blood reperfusion and was similar to an ischemia–reperfusion state. Serum CK and mitotic activity in the muscle consistently increased, and damaged muscle fibers that reacted positively to anti-GPX antibody were also observed after exercise. Serial changes in total SOD, GPX, and CAT activities were biphasic and exhibited peaks immediately and 24–72 h after exercise. The first increase was caused by a repeated ischemia–reperfusion-like state following weight-lifting exercise, and the second was dependent on the accumulation of infiltrated phagocytic cells at the damaged portions. These results suggest that ROS-induced muscle fiber damage occurred as a consequence of weight-lifting exercise.     

Erythrocyte antioxidant enzymes in patients with cataract

The pathogenesis of cataract has been found to be influenced by a number of factors including oxidative stress. Catalase, glutathione peroxidase (GPX), and superoxide dismutase (SOD) are some of the antioxidant enzymes that protect the body from oxidative damage. The present study investigates the activities of erythrocyte catalase, GPX, and SOD with respect to senile cataract (non-diabetic cataract) and osmotic cataract (diabetic cataract) in a Sri Lankan population. One hundred and two non-diabetic subjects (50 with cataract and 52 non-cataract) and 106 diabetic subjects (56 with cataract and 50 non-cataract) were recruited into the study. Erythrocyte catalase, GPX, and SOD activities were assayed and the data were analysed by t-test (p <0.05 for significance). In the non-diabetic group, significantly low levels of catalase, GPX, and SOD activities were associated with cataract when compared with non-cataract. No significant changes in catalase, GPX, and SOD activities were observed in the diabetic group between cataract and non-cataract. Senile cataract (non-diabetic cataract) was associated with significantly low levels of erythrocyte catalase, GPX, and SOD when compared with osmotic cataract (diabetic cataract). Positive correlations were observed between catalase and SOD (r = 0.75), catalase and GPX (r = 0.63), and SOD and GPX (r = 0.59) in subjects with senile cataracts. Our results indicate that erythrocyte antioxidant enzyme levels are decreased in senile cataract as opposed to osmotic cataract. Assays of these erythrocyte enzyme activities could provide a marker to identify individuals predisposed to senile cataract.     

Effects of aerobic exercise training on antioxidant enzyme activities and mRNA levels in soleus muscle from young and aged rats

The aim of this study was to investigate the effect of aerobic exercise training on activities and mRNA levels of catalase (CAT), glutathione peroxidase (GPX), Cu,Zn- and Mn-superoxide dismutases (SOD), TBARS content, and xanthine oxidase (XO) activity, in soleus muscle from young and aged rats. The antioxidant enzyme activities and mRNA levels were markedly increased in soleus muscle with aging. TBARS content of soleus muscle from the aged group was 8.3-fold higher as compared with that of young rats. In young rats, exercise training induced an increase of all antioxidant enzyme activities, except for Cu,Zn-SOD. XO also did not change. The TBARS content was also increased (2.9-fold) due to exercise training in soleus muscle from young rats. In aged rats, the activities of CAT, GPX and Cu,Zn-SOD in the soleus muscle did not change with the exercise training, whereas the activities of Mn-SOD (40%) and XO (27%) were decreased. The mRNA levels of Mn-SOD and CAT were decreased by 42% and 24%, respectively, in the trained group. Exercise training induced a significant decrease of TBARS content (81%) in the soleus muscle from aged rats. These findings support the proposition that exercise training presents an antioxidant stress effect on skeletal muscle from both young and aged rats.     

Red cell superoxide dismutase, glutathione peroxidase and catalase in Down syndrome patients with and without manifestations of Alzheimer disease

The activities of red blood cell enzymes that scavenge the superoxide radical and hydrogen peroxide were measured in severely to profoundly retarded adult Down syndrome (DS) patients with and without manifestations of Alzheimer disease (AD), and control individuals matched for sex, age, and time of blood sampling. Cu,Zn superoxide dismutase (SOD-1) and glutathione peroxidase (GSHPx) activities were significantly elevated (1.39-fold and 1.24-fold, respectively) in DS individuals without AD. When an adjustment was made for the SOD gene dosage effect, DS patients with AD manifestations had significantly lower SOD levels than the matched control individuals. In contrast, DS patients with and without AD had a similar elevation in GSHPx (an adaptive phenomenon). The mean catalase (CAT) activity was no different in DS and control individuals; however, in a paired regression analysis, DS patients without AD had marginally lower CAT activity than control individuals, whereas DS patients with AD had slightly but not significantly higher CAT activity. Thus, AD manifestations in this DS population are associated with changes in the red cell oxygen scavenging processes.     

Oxidative stress induced by intermittent exposure at a simulated altitude of 4000 m decreases mitochondrial superoxide dismutase content in soleus muscle of rats

The effects were examined of 6-month intermittent hypobaric (4000 m) exposure on the antioxidant enzyme systems in soleus and tibialis muscles of rats. At the end of the 6-month experimental exposure, the six rats in both the exposed group and the control group were sacrificed. Immunoreactive mitochondrial superoxide dismutase (Mn-SOD) contents were measured as well as the activities of antioxidant enzymes [Mn-SOD, cytosolic SOD (Cu,Zn-SOD), catalase (CAT), and glutathione peroxidase (GPX)]. Thiobarbituric acid-reactive substances (TBARS) were also determined as an indicator of lipid peroxidation. The high altitude exposure resulted in a marked increase in TBARS content in soleus muscle, suggesting increased levels of oxygen free radicals. Conversely, significant decreases in both Mn-SOD content and activity in solens muscle were oted affer exposure. Such trends were not noticed in tibialis muscle. On the other hand, no significant changes in Cu,Zn-SOD, CAT, or GPX were observed in either muscle. These results suggested that the increases in lipid peroxidation were most probably a result of decreased Mn-SOD function which was more depressed in oxidative than in glycolytic muscle.     

Enhanced plasminogen activator inhibitor-1 expression in transgenic mice with hepatocyte-specific overexpression of superoxide dismutase or glutathione peroxidase

In this study, we developed a double-transgenic mouse model allowing hepatocyte-specific and regulated expression of the redox-modifying enzymes copper/zinc superoxide dismutase (SOD) and glutathione peroxidase (GPX) by using a tetracycline-regulatable gene expression system. Within this system, the SOD and GPX level can be regulated deliberately by addition or removal of doxycycline hydrochloride to the drinking water. As reactive oxygen species (ROS) have been implicated in a number of pathological conditions, such as atherosclerosis, thrombosis, or liver fibrosis, processes that are also frequently associated with enhanced levels of plasminogen activator inhibitor-1 (PAI-1), it was the aim of the present study to investigate the influence of SOD and GPX overexpression on the regulation of PAI-1. PAI-1 mRNA and protein levels in tetracycline transactivator-dependent SOD-overexpressing double-transgenic mice reached values 2.5- to threefold above the normal mRNA level. By applying doxycycline, a deinduction of the PAI-1 levels was observed. By using the same protocol, PAI-1 mRNA and protein levels were enhanced in GPX double-transgenic mice, and again this response was blunted by the addition of doxycycline. These studies provide some new information regarding the role of ROS within the proteolytic processes in hepatocytes that require PAI-1.     

Increased lipoperoxide value and glutathione peroxidase activity in blood plasma of Type 2 (non-insulin-dependent) diabetic women

Summary The lipoperoxide values and glutathione peroxidase activity in blood plasma, along with the glutathione peroxidase, catalase and cupro-zinc superoxide dismutase activities in erythrocytes were investigated in 60 women with Type 2 (non-insulin-dependent) diabetes mellitus and in 71 healthy women. The mean lipoperoxide value and the mean plasma glutathione peroxidase activity in the diabetic patients were significantly higher than those in the control subjects (lipoperoxidep<0.001, plasma glutathione peroxidase activityp<0.01). The plasma glutathione peroxidase activities did not, however, correlate with the plasma lipoperoxide values. The erythrocyte glutathione peroxidase activity was approximately ten times higher than that of the plasma glutathione peroxidase activity, nor did they correlate with each other. In contrast to the findings of other authors on the activities of the protective enzymes in erythrocytes against oxidative damage, there were no significant differences of erythrocytes glutathione peroxidase, catalase and superoxide dismutase activities between diabetic and control women.Abbreviation SOD superoxide dismutase     

Changes in gene expression level for defense system enzymes against oxidative stress and glutathione level in rat administered paraquat

The herbicide paraquat (PQ) forms reactive oxygen species during enzymatic activation. We examined the effect of PQ on the relative levels of gene expression of antioxidant enzymes and glutathione (GSH) status in lungs of rats exposed to 20 mg/kg PQ. At 16 h after PQ intake, the mRNA expression level of glutathione reductase (GR) showed the greatest increase, and those of catalase (CAT) and manganese-superoxide dismutase (MnSOD) showed more modest increases. In contrast, PQ had little or no effect on the levels of mRNAs for copper/zinc-superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPX). These findings indicate that CAT and MnSOD are coordinated and play a major role in removal of oxidants. On the other hand, PQ caused a significant increase in the GSH level in the lungs, but not in the liver. This increase in the lungs was, at least in part, caused by stimulation of the gamma-glutamylcysteine synthetase gene. However, the expression of GPX mRNA was not stimulated as described above. Because GSH is a substrate for GPX and serves as a scavenger of hydroxyl radicals, the increase in GSH as well as GR expression may be insignificant. This imbalance may be a result of oxidative stress due to PQ.     

The effect of exhaustive exercise on the antioxidant enzyme system in skeletal muscle from calcium-deficient rats

 The aim of the current study was to elucidate the synergism of dietary calcium restriction and exhaustive exercise in the antioxidant enzyme system of rat soleus muscle, and to investigate the involvement of neutrophils in exercise-induced muscle damage. Forty-eight male Wistar rats were assigned to the following groups: control (C) or calcium-restricted [1 month (1 M) or 3 months (3 M)]. Each group was subdivided into acutely exercised or non-exercised groups. Soleus muscle from each rat was analysed to determine the levels of antioxidant enzymes [Mn-superoxide dismutase (SOD), Cu,Zn-SOD, glutathione peroxidase (GPX), and catalase (CAT)]. Dietary calcium restriction resulted in calcium deficiency and upregulated the antioxidant enzymes examined except GPX. Conversely, exhaustive exercise significantly decreased GPX and CAT, but not SODs activities in the calcium-restricted (1 M and/or 3 M) rats. Contents of immunoreactive Mn-SOD and Cu,Zn-SOD were only increased in the 3 M rats. During calcium restriction, the mRNA expression of both forms of SOD showed initial upregulation, followed by downregulation. Exhaustive exercise significantly increased the mRNA expressions only in the 3 M rats. Moreover, exhaustive exercise markedly increased myeloperoxidase activity in soleus muscles from the 1 M and 3 M rats compared with the C rats, and significantly enhanced the ability of neutrophils to generate superoxide in the 3 M rats. The results demonstrate that dietary calcium restriction upregulates certain antioxidant enzyme activities in rat soleus muscle, indicating an enhanced resistance to potential increases in intracellular reactive oxygen species. The results also suggest that exhaustive exercise may cause oxidative damage in soleus muscle of calcium-deficient rats through the activation of neutrophils. Received: 4 August 1997 / Received after revision: 29 September 1997 / Accepted: 26 November 1997     

Effects of castration and testosterone replacement on the antioxidant defense system in rat left ventricle

There is strong evidence that oxidative stress plays a key role in the pathophysiology of several cardiovascular diseases. On the other hand, the presence of specific receptors for androgens and estrogens in the myocardium implies that sex hormones play a physiological role in cardiac function, myocardial injury, and the regulation of the redox state in the heart. The present study was designed to determine whether castration and androgen replacement result in changes in the capacity of the antioxidant defense system in the left ventricle (LV) of adult male rats. To assess this, the activities of antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPX], catalase [CAT], and glutathione reductase [GR]), concentrations of nonenzymatic antioxidants (reduced glutathione [GSH] and alpha- and gamma-tocopherols), and oxidative stress biomarkers (tissue sulfhydryl groups, protein nitrotyrosine levels, and lipid peroxidation) were measured in castrated animals (CAS), castrates replaced with testosterone (CAS+T), and sham-operated controls (Sham). Testosterone was not detectable in serum from gonadectomized rats. The results indicate that castration significantly and negatively affected the antioxidant status of rat LV, as evidenced by a significant decline in activities of all antioxidant enzymes, by a tendency toward lower levels of GSH and protein thiol groups, and by enhanced lipid peroxidation and higher nitrotyrosine concentrations in left ventricular tissue. Increases in LV tissue concentrations of alpha- and gamma-tocopherols seem to be a compensatory response to enhanced oxidative stress induced by gonadectomy. The reestablishment of physiological serum testosterone level by androgen replacement resulted in a tendency toward a further decrease in the antioxidant defense status in the LV tissue.