Antioxidant Defense Status Research Articles

An integrated approach to assessing nitroso-redox balance in systemic inflammation

Most studies examining the metabolic fate of NO during systemic inflammation have focused on measuring the quantitatively predominating, stable anions nitrite and nitrate within the circulation. However, these are not necessarily the NO-related products that govern NO metabolism and signaling in tissues. We assessed all major NO derivatives temporally in blood and vital organs during inflammation and explored their relationship to insult severity and redox status. Male rats receiving intraperitoneal endotoxin or vehicle were sacrificed for organ and blood sampling between 0 and 24 h. Endotoxin induced transient and organ-specific changes in a variety of NO metabolites. Nitrite and nitrate increased, peaking at 8 and 12 h, respectively. S- and N-nitrosation and heme-nitrosylation products also peaked at 8 h; these posttranslational protein modifications were associated with decreased myocardial function (echocardiography). Evidence of oxidative stress and systemic inflammation was also obtained. The rise in most NO derivatives was proportional to insult severity. All metabolite levels normalized within 24 h, despite evidence of persisting myocardial dysfunction and clinical unwellness. Our findings point to a complex interplay between NO production, antioxidant defense, and redox status. Although the precise (patho)physiologic roles of specific NO derivatives and their diagnostic/prognostic utility await further investigation, nitroso species in erythrocytes are the most sensitive markers of NO in systemic inflammation, detectable before clinical symptoms manifest.

The influence of dietary supplementation of arachidonic acid on prostaglandin production and oxidative stress in the Pacific oyster Crassostrea gigas

In a previous study, dietary supplementation with arachidonic acid (ARA) to oysters Crassostrea gigas increased haemocyte numbers, phagocytosis, and production of reactive oxygen species level (ROS) by haemocytes ( Delaporte et al., 2006). To assess if the observed stimulation of these cellular responses resulted from changes of ARA-related prostaglandin (PG) production, we analysed prostaglandin E2 metabolite (PGEM) content on the same oysters fed three levels of ARA. Dietary supply of polyunsaturated fatty acids (PUFA) could also induce an oxidative stress that could similarly increase cellular responses; therefore, two indicators of oxidative stress were analysed: peroxidation level and antioxidant defence status. Together the observed positive correlation between ARA and PGEM levels and the absence of lipid peroxidation and antioxidant activity changes supports the hypothesis of an immune stimulation via PG synthesis. Although ARA proportion in oyster tissues increased by up to 7-fold in response to ARA dietary supplementation, peroxidation index did not change because of a compensatory decrease in n-3 fatty acid proportion, mainly 22:6n-3. To further confirm the involvement of PG in the changes of haemocyte count, phagocytosis and ROS production upon ARA supplementation, it would be interesting to test cyclooxygenase and lipooxygenase inhibitors in similar experiments.

Effect of long term intake of aspartame on antioxidant defense status in liver

The present study evaluates the effect of long term intake of aspartame, the artificial sweetener, on liver antioxidant system and hepatocellular injury in animal model. Eighteen adult male Wistar rats, weighing 150–175g, were randomly divided into three groups as follows: first group was given aspartame dissolved in water in a dose of 500mg/kg b.wt.; the second group was given a dose of 1000mg/kg b.wt.; and controls were given water freely. Rats that had received aspartame (1000mg/kg b.wt.) in the drinking water for 180days showed a significant increase in activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT). The concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly reduced in the liver of rats that had received aspartame (1000mg/kg b.wt.). Glutathione was significantly decreased in both the experimental groups. Histopathological examination revealed leukocyte infiltration in aspartame-treated rats (1000mg/kg b.wt.). It can be concluded from these observations that long term consumption of aspartame leads to hepatocellular injury and alterations in liver antioxidant status mainly through glutathione dependent system.

Features of lipid peroxidation in rats of different age after postinfarction cardiosclerosis

The results of lipid peroxidation (LP) system research in 4- and 12-month-old rats against the backdrop of postinfarction cardiosclerosis are presented in this study. It has been shown that age-related changes in LP and antioxidant enzyme activity were observed in the long term after experimental myocardium infarction. Moreover, a difference in the intensity of LP processes was discovered in intact animals of the given age groups. Probably, these age-related properties result in a different LP intensity and antioxidant defense status under postinfarction heart remodeling.

Oxidative and antioxidative defense system in testicular torsion/detorsion

Aim:The present study was aimed to assess the early effects of ischemia/reperfusion injury on the oxidants and anti-oxidant defense status in rat testicular tissue by measuring MDA, glucose-6-phosphte dehydrogenase activity and reduced glutathione levels in a designated time frame sequel to reperfusion. Animals were divided randomly into six groups (12 animals per group) in the following order: Group I: Sham-operated control group (Cso) without the application of the torsion. Group 2: Torsion-induced ischemia group (T30 m): Ischemia was induced through the torsion of spermatic cord for a period of 30 min. Group 3: One hour reperfusion group after detorsion (T30 mR1 h). Group 4: Twenty-four hour reperfusion group after detorsion (T30 mR24 h). Group 5: Forty-eight hours reperfusion group after detorsion (T30mR48h). Group 6: One week reperfusion group after detorsion (T30mR1wk). Results and Discussion:The oxidant-antioxidant system of the testicular tissue is altered during torsion as well as detorsion which results in the altered activities involved in the key enzyme of hexose monophosphate shunt pathway, glucose 6 phosphate dehydrogenase activity along with a reduction of glutathione (G.SH) content. The increase in G6PDH activity during torsion and followed by an increase in detorsion indicates the tissue's response to counter the oxidant stress caused by reduced blood supply. Continued exposure to such oxidant stressed physiological state of a tissue may lead to decreased capacity of the tissue to perform its physiological function such as testicular steroidogenesis and spermiogenesis shown in the present study.

Diaphragmatic Breathing Reduces Exercise‐Induced Oxidative Stress

Diaphragmatic breathing is relaxing and therapeutic, reduces stress, and is a fundamental procedure of Pranayama Yoga, Zen, transcendental meditation and other meditation practices. Analysis of oxidative stress levels in people who meditate indicated that meditation correlates with lower oxidative stress levels, lower cortisol levels and higher melatonin levels. It is known that cortisol inhibits enzymes responsible for the antioxidant activity of cells and that melatonin is a strong antioxidant; therefore, in this study, we investigated the effects of diaphragmatic breathing on exercise-induced oxidative stress and the putative role of cortisol and melatonin hormones in this stress pathway. We monitored 16 athletes during an exhaustive training session. After the exercise, athletes were divided in two equivalent groups of eight subjects. Subjects of the studied group spent 1 h relaxing performing diaphragmatic breathing and concentrating on their breath in a quiet place. The other eight subjects, representing the control group, spent the same time sitting in an equivalent quite place. Results demonstrate that relaxation induced by diaphragmatic breathing increases the antioxidant defense status in athletes after exhaustive exercise. These effects correlate with the concomitant decrease in cortisol and the increase in melatonin. The consequence is a lower level of oxidative stress, which suggests that an appropriate diaphragmatic breathing could protect athletes from long-term adverse effects of free radicals.

Alteration of antioxidant defense status precedes humoral immune response abnormalities in macrosomia

SummaryBackgroundThis study aimed to investigate whether the anomalies affecting the antioxidant and humoral immune defenses could start at birth and to check whether the decrease in antioxidant defenses may precede the immune abnormalities in macrosomic newborns.Material/MethodsThirty macrosomic and 30 sex-matched control newborns were recruited for a retrospective case-control study at the Maghnia Maternity Hospital of Tlemcen Department (Algeria).ResultsThe serum IgG levels were similar in both groups. However, plasma ORAC, albumin, vitamin E, SOD, CAT and GSH-Px levels were significantly decreased in macrosomic as compared to control newborns, yet no difference was observed after adjustment for weight. Additionally, serum concentrations of complement C3, MDA and XO were significantly higher in macrosomic as compared to controls before adjustment for weight. Moreover, macrosomia was significantly associated with high levels of complement C3 (OR=8, p=0.002); whereas no association with those of IgG was observed (OR<1, p>0.05). Furthermore, macrosomia was significantly associated with low levels of ORAC (OR=4.96, p=0.027), vitamin E (OR=4.5, p=0.018), SOD (OR=6.88, p=0.020) and CAT (OR=5.67, p=0.017), and with high levels of MDA (OR=10.29, p=0.005).ConclusionsAbnormalities of the humoral defense system in excessive weight could be preceded by alterations of the anti-oxidative defense and by inflammatory response and activation of innate immunity at birth. Additionally, excessive weight could be a potential factor contributing to decreased anti-oxidative capacity and increased oxidative stress.

Modulation of Bcl-2-related protein expression in pancreatic beta cells by pro-inflammatory cytokines and its dependence on the antioxidative defense status

Pro-inflammatory cytokines are key mediators in the selective and progressive destruction of insulin-producing beta cells during type 1 diabetes development. However, the mechanisms of cytokine-induced beta cell apoptosis are not fully understood.This study demonstrates that pro-inflammatory cytokines strongly modified the expression of the anti-apoptotic protein Bcl-2 and the pro-apoptotic BH3-only proteins Bad, Bim, and Bid in primary rat islets and insulin-producing RINm5F cells. Overexpression of mitochondrially located catalase (MitoCatalase) specifically increased basal Bcl-2 and decreased basal Bax expression, suppressed cytokine-mediated reduction of Bcl-2, and thereby prevented the release of cytochrome c, Smac/DIABLO and the activation of caspase-9 and -3. Thus, cytokine-mediated decrease of Bcl-2 expression and the sequentially changed Bax/Bcl-2 ratio are responsible for the release of pro-apoptotic mitochondrial factors, activation of caspase-9, and ultimately caspase-3.These results indicate that activation of the intrinsic/mitochondrial apoptosis pathway is essential for cytokine-induced beta cell death and the mitochondrial generation of reactive oxygen species, in particular mitochondrial hydrogen peroxide, differentially regulates the Bax/Bcl-2 ratio.

Iridoid extracts from Ajuga iva increase the antioxidant enzyme activities in red blood cells of rats fed a cholesterol-rich diet

The lyophilized aqueous extract of Ajuga iva (Ai) is able to reduce oxidative stress, which may prevent lipid peroxidation in hypercholesterolemic rats. Iridoids (I) were isolated from Ai. We hypothesized that the antioxidant defense status in red blood cells (RBC) and tissues in rats fed a cholesterol-rich diet and treated with Ai may be correlated to these compounds. Male Wistar rats (n = 32) weighing 120 +/- 5 g were fed a diet containing 1% cholesterol for 15 days. After this phase, hypercholesterolemic (HC) rats were divided into groups, fed the same diet, and received either the same or different doses (5, 10, or 15 mg/kg body weight by intraperitoneal injection) of I for 15 days. Compared with the HC group, total cholesterol value was 1.4- and 1.2-fold lower in the I(5)-HC and I(10)-HC groups. Serum thiobarbituric acid reactive substance content was 2.3-, 2.9-, and 3-fold lower in the I(5)-HC, I(10)-HC, and I(15)-HC groups compared with the HC group. In RBC, glutathione peroxidase, glutathione reductase, and superoxide dismutase activities were significantly higher in the I(5)-HC, I(10)-HC, and I(15)-HC groups than the HC group. Liver, heart, and muscle glutathione peroxidase and superoxide dismutase activities were significantly higher in the groups treated with I than the HC group. Muscle glutathione reductase activity was increased 1.4-fold in the I(5)-HC, 1.5-fold in the I(10)-HC, and 1.5-fold in the I(15)-HC group. In HC rats, different doses of I increase the antioxidant enzyme activities in RBC and act differently in tissues. Treatment with I may play an important role in suppressing oxidative stress caused by dietary cholesterol and, thus, may be useful for the prevention and/or early treatment of hypercholesterolemia.

PTU-induced hypothyroidism modulates antioxidant defence status in the developing cerebellum

The objective of the present study was to evaluate the effect of 6-n-propylthiouracil (PTU)-induced hypothyroidism on oxidative stress parameters, expression of antioxidant defence enzymes, cell proliferation and apoptosis in the developing cerebellum. PTU challenged neonates showed significant decrease in serum T3 and T4 levels and marked increase in TSH levels. Significantly elevated levels of cerebellar H2O2 and lipid peroxidation were observed in 7 days old hypothyroid rats, along with increased activities of superoxide dismutase and glutathione peroxidase and decline in catalase activity. In 30 days old hypothyroid rats, a significant decline in cerebellar lipid peroxidation, superoxide dismutase and glutathione peroxidase activity and expression was observed along with an up-regulation in catalase activity and expression. Expression of antioxidant enzymes was studied by Western blot and semi-quantitative rt-PCR. A distinct increase in cell proliferation as indicated by proliferating cell nuclear antigen (PCNA) immunoreactivity was observed in the internal granular layer of cerebellum of 7 days old hypothyroid rats and significant drop in PCNA positive cells in the cerebellar molecular layer and internal granular layer of 30 days old PTU treated rats as compared to controls. In situ end labeling by TUNEL assay showed increased apoptosis in cerebellum of hypothyroid rats in comparison to controls. These results suggest that the antioxidant defence system of the developing cerebellum is sensitive to thyroid hormone deficiency and consequent alterations in oxidative stress status may play a role in regulation of cell proliferation of the cerebellum during neonatal brain development.

A comparative study on the effect of homobrassinolide and gibberellic acid on lipid peroxidation and antioxidant status in normal and diabetic rats

Dietary content of phytohormones may potentially influence metabolic processes in animal cells. This study therefore aimed to investigate the effect of two plant growth regulators homobrassinolide (HB) and gibberellic acid (GBA) on the antioxidant defense status and lipid peroxidation level in the tissues of normal and streptozotocin- induced diabetic rats. Normal and diabetic rats (Albino –wistar strain) were administered 50μg HB and GBA intradermally each day for seven days and their tissue and blood levels of malondialdehyde (MDA), 4-hydroxy-2-nonenol (4-HNE), reduced glutathione (GSH) content and catalase (CAT) activity were determined. Subchronic treatment of rats with HB reduced lipid perioxidation and elevated antioxidant defense whereas GBA caused enhancement of lipid peroxidation and reduction of antioxidant defense in treated animals compared to the control rats.

Caffeic acid modulates ultraviolet radiation-B induced oxidative damage in human blood lymphocytes

Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppressin in the human skin cells. These biological changes are responsible for photocarcinogenesis and photoaging. Normal lymphocytes are highly sensitive to the damaging effect of UV-radiation and undergo cell death. In the present study, the photoprotective effect of caffeic acid (3,4-dihydroxy cinnamic acid), a dietary phenolic compound, has been examined in the UVB (280–320) irradiated human blood lymphocytes. Lymphocytes pretreated with increasing concentration of caffeic acid (l, 5 and 10 μg/mL) for 30 min were irradiated and lipid peroxidation, antioxidant defence status, cell viability (by MTT assay) and DNA damage (by comet assay) were examined. UVB-irradiation causes increased levels of lipid peroxidation, DNA damage and decreased antioxidant status, cell viability in human lymphocytes. Caffeic acid pretreatment significantly reduced the levels of lipid peroxidation markers i.e. thiobarbituric acid reactive substance (TBARS), lipid hydroperoxide (LPH), conjugated diene (CD) and decreased DNA damage (tail length and % tail DNA) in UVB-irradiated lymphocytes. Further, caffeic acid pretreatment significantly maintains antioxidant status and decreased UVB-induced cytotoxicity. The maximum dose of caffeic acid (l0 μg/mL) normalized the UVB induced cellular changes indicating the photoprotective effect of caffeic acid in irradiated lymphocytes.

Chlorogenic Acid Reduces Oxidative Stress in Rpe Cells

Our purpose was to determine whether chlorogenic acid (CGA) influence the levels of antioxidant defense status by monitoring the activity of catalase (CAT), of superoxide dismutase (SOD), reduced glutathione (GSH) content and the generation of intracellular reactive oxygen species (ROS). Confluent RPE cells (D407) were preincubated with l00 µM chlorogenic acid and after phenolic acid removal, cells were oxidatively challenged with 500µM H2O2. The dose of l00µM chlorogenic acid did not induce morphological changes in RPE cells, indicating a viability of 88% comparing with control after 24h of treatment. CGA treatment has not cytotoxic effect and reduces the cytotoxic effect of hydrogen peroxide in RPE cells. Chlorogenic acid treatment (1) up regulates the antioxidant enzymes activities CAT and SOD in RPE, especially in oxidatively stressed cells; (2) determine an increase of reduced glutathione concentration and, (3) decrease intracellular ROS generation in RPE cells subjected to oxidative stress. Chlorogenic acid could be a potential antioxidant agent for RPE cells, protecting them by oxidative stress.

Protective role of luteolin on the status of lipid peroxidation and antioxidant defense against azoxymethane-induced experimental colon carcinogenesis

The modifying effect of dietary exposure to a flavonoid, luteolin (LUT) during the azoxymethane (AOM)-induced colon carcinogenesis was investigated in this study. Aberrant crypt foci (ACF), lipid peroxidation (LPO), enzymic and non-enzymic antioxidants and histopathological analysis were performed. Colon carcinogenesis was induced by injecting 15 mg/body kg weight of AOM, intraperitoneally (i.p.), once in a week for 3 weeks in male Balb/c mice. AOM-induced mice were treated with LUT (1.2 mg of LUT/kg body weight/day orally). After the experimental period, frequency of ACF, levels of thiobarbutaric acid reactive substances (TBARS) and hydroxy radical (OH˙) were found to be increased, whereas glutathione (GSH), Vitamins C, E and A were decreased in the plasma and colon of AOM-induced mice. However, LUT treatment to AOM-induced mice significantly decreased the incidence of ACF, levels of TBARS and OH˙ with a concordant increase in non-enzymic antioxidants in plasma and colon tissue. The activities of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were found to be decreased due to the induction of colon cancer in mouse. LUT treatment ameliorated the activities of these antioxidant enzymes. The histological study revealed a significant increase in the enlarged nuclei and hyperchromatism of cells in AOM-induced mice whereas LUT significantly reduced the signs in the colon. The immunohistochemical expression of MDA-DNA adduct was studied. In AOM-induced group, the expression was increased and treatment with LUT decreased significantly. The present study depicts that LUT can act as an effective chemopreventive agent against colon cancer.

Lipid peroxidative stress and antioxidant defence status during ontogeny of rainbow trout (Oncorhynchus mykiss)

The objective of the present study was to characterise some important antioxidant enzymes and their relationships with retinoids and lipid peroxidation during rainbow trout (Oncorhynchus mykiss) early development. Eggs were incubated at 7 degrees C until the swim-up stage whereupon fry were fed two semi-purified diets with 0% (CO) and 8% (OX) oxidised lipid respectively for 2 months at 17 degrees C. The activities and gene expression of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were determined as well as the levels of retinoids, F2-isoprostanes and lipid-soluble fluorescent products (LSFP) at various developmental stages. Only SOD had a detectable activity in embryos which increased during development and was linked with an increase of mitochondrial (SOD2) and cytosolic (SOD1) gene expression. SOD1 and SOD2 mRNA were more abundant in fry fed OX than in fry fed CO. CAT activity and gene expression also increased during development and were higher in fry fed OX compared with fry fed CO. Activity of Se-dependent GPX (Se-GPX) increased during development. The gene expression of cytosolic Se-GPX (GPX1) increased from hatching to 2-month-fed fry. Both phospholipid-hydroperoxide GPX and GPX1 genes were more expressed in fry fed OX than in fry fed CO. Retinoids decreased during development and, by 2 months, were lowered in fry fed OX compared with those fed CO. The levels of LSFP were higher in fry fed OX compared with fry fed CO. The present study demonstrates that antioxidant defence systems are active all through the development of rainbow trout and modulated by feeding oxidised lipid.

Wheat Germ Supplementation of a Low Vitamin E Diet in Rats Affords Effective Antioxidant Protection in Tissues

Background: Oxidative stress is implicated in the etiology of many diseases, but most of clinical trials failed to demonstrate beneficial effects of antioxidant supplementation.Methods: In the present experiment, we assessed the mean-term effect of wheat germ supplementation, as a dietary source of vitamin E, on antioxidant protection in rat.Results: Feeding rats a 20% wheat germ diet significantly increased plasma and liver vitamin E levels, compared to the low vitamin E basal diet. Concurrently, wheat germ diet consumption strongly decreased the susceptibility of heart and liver lipids to oxidation, as well as the plasma. Wheat germ feeding did not change triglycerides (TG) nor total cholesterol concentrations in plasma or liver, resulting in higher vitamin E/ TG ratio compared to controls. Similar results were found with a diet in which wheat germ oil provided the same amount of vitamin E.Conclusions: Wheat germ appears thus very effective to improve antioxidant defense status, especially in tissues, irrespective of modifications of lipids status.

Effect of Nonsteroidal Anti-Inflammatory Drugs and the Procarcinogen 1,2-Dimethylhydrazine on the Antioxidant Defense System

The present study was designed to evaluate the effects of three nonsteroidal anti-inflammatory drugs (NSAIDs) with varying cycloxygenase selectivities on the small intestinal antioxidant enzyme status and surface characteristics during 1,2-dimethylhydrazine (DMH) administration. Male Sprague-Dawley rats were divided into five different groups: Group 1 (control, vehicle treated); group 2 (DMH treated, 30 mg/kg body weight/week, subcutaneously); group 3 (DMH + aspirin 60 mg/kg body weight); group 4 (DMH + celecoxib 6 mg/kg body weight); group 5 (DMH + etoricoxib 0.64 mg/kg body weight). Postmitochondrial fraction were isolated from the intestinal segments and different oxidative parameters and other parameters studied, such as the lipid peroxides, reduced and total glutathione, superoxide dismutase, catalase, glutathione reductase, glutathione S-transferase, nitric oxide, citrulline, and nucleic acids. At the end of 6 weeks of treatment, the results indicated a significant alteration in the antioxidative defense status of the intestine in the presence of the procarcinogen DMH, which was restored with the administration of NSAIDs. The study, therefore, suggests a possible mechanism for the chemopreventive effects of NSAIDs against the experimental intestinal cancer in rats.

Changes in antioxidant defense status in hypercholesterolemic rats treated with Ajuga iva

The aim of the study was to investigate the effect of aqueous extract of Ajuga iva (Ai) on serum and tissues lipid peroxidation as well as antioxidant enzymes activities in red blood cells (RBC) and tissues, in high hypercholesterolemic rats (HC). Male Wistar rats (n=12) were fed on 1% cholesterol-enriched diet for 15d. After this adaptation phase, hypercholesterolemic rats (total cholesterol=6.5+/-0.6mol/l) were divided into two groups fed the same diet and treated or not with Ai for 15d. Thiobarbituric acid reactive substances (TBARS) concentrations in serum, LDL-HDL(1), HDL(2) and HDL(3) were respectively, 5-, 7.8-, 2.3- and 5-fold lower in Ai treated than untreated hypercholesterolemic groups. TBARS concentrations were 1.4-fold lower in heart and 2.8-fold higher in kidney in Ai-HC treated than untreated HC group. Superoxide dismutase activity was respectively, 1.2- and 1.4-fold higher in RBC and muscle in Ai treated than untreated group. In RBC, Ajuga iva treatment enhanced glutathione peroxidase (GSH-Px) (+9%) and glutathione reductase (GSSH-Red) (+12%) in Ai-HC treated than untreated HC group. GSSH-Red activity was 1.4- and 1.5-fold higher in adipose tissue and heart, respectively and 3.7-fold lower in kidney in Ai treated than untreated group. Liver catalase activity was 1.6-fold higher in Ai treated than untreated group. Adipose tissue and muscle total glutathione content represented in Ai treated group 35% and 36% of the value noted in untreated group. Nitric oxide values of liver, adipose tissue and heart were 3.3-, 2.5- and 3.4-fold higher in Ai-HC than HC group. Ajuga iva treatment enhanced alpha-tocopherol contents (+25%) in Ai treated than untreated group. In conclusion, Ajuga iva treatment is more effective to improve the antioxidant capacity of RBC than that of tissues. Indeed, Ai is able to reduce the oxidative stress in hypercholesterolemic rats by increasing the antioxidant enzymes activity.

The status of antioxidant defences in Glucose-6-phosphate dehydrogenase deficient patients. The role of antioxidants to ameliorate hemolytic crisis

In human, G6PD deficiency is the most common enzymopathy affecting over 400 million people throughout the world. It is associated with higher potential for oxidative damage due to chronic redox imbalance in red cells that often results in clinical manifestation of mild to severe hemolysis. The NADPH product of G6PD is required for the reductive biosynthetic reactions as well as for the stability of catalase, and the preservation of the reduced form of glutathione (GSH). The aim of this study was to clarify the role of G6PD in cellular antioxidant defense; the level of glutathione, catalase, NADPH and estimate the level of malondialdehyde which reflect the oxidative stress across the cell membrane. Also to study the effect of antioxidant treatment (vitamins C and E) to ameliorate high sensitivity of red cells to oxidative stress. This study was carried out on fifty G6PD-deficient children during the attack. The children were classified into two groups: Group 1: received blood transfusion only, and considered as an antioxidant-untreated group. Group 2: Received blood transfusion as group I in addition to antioxidant therapy (antioxidant-treated group), and healthy control subjects as control group. Our study proved that hemolytic attack in G6PD deficient patients is due to a concomitant impairment of the two main mechanisms of detoxification of H2O2 in RBCs; GSH system and catalase. The most important finding in this study is the efficiency of treatment with a combination of vitamin E and vitamin C may improve antioxidant status in G6PD deficient patients and in reducing the symptoms of hemolytic crises.Egyptian Journal of Biochemistry and Molecular Biology Vol. 25 (2) 2007: pp. 114-133

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.