Antioxidant Status and Oxidative Stress in Patients with Chronic ITP

The aim of this study was to establish the antioxidant status and oxidative stress in adult patients with chronic idiopathic thrombocytopenic purpura (ITP). Eighty‐four patients diagnosed with chronic ITP were studied. Fifty‐eight age‐matched healthy subjects were selected as controls. Serum nitrogen monoxide ( NO), oxidized glutathione (GSSG), malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase(SOD), hydrogen peroxide enzyme (CAT), glutathione peroxidase (GSH‐Px), glutathione (GSH) were evaluated by enzyme‐linked immunosorbent assay (ELISA). It was found that serum SOD, CAT, GSH‐Px, GSH, TAS levels were significantly lower in patients with chronic ITP than controls (all P < 0.05), while serum NO, GSSG, MDA, TOS values were significantly higher (P < 0.05). The number of platelet showed a negative correlation with NO, GSSG, MDA, TOS, respectively,while platelet number showed a positive correlation with SOD, CAT, GSH‐Px, GSH, TAS. These findings suggested that oxidants were increased and antioxidants were decreased in patients with chronic ITP, these may be prominent factors in destructing the platelet membrane. The scavenging of oxygen radical provides a theoretical basis for the treatment of ITP patients.     

Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats

The toxicity of aminoglycosides including gentamicin (GEN), the most widely used drug in this category, is believed to be related to the generation of reactive oxygen species (ROS) in the kidney. Aminoguanidine (AG) is known as an effective antioxidant and its free radical scavenger effects may protect GEN-induced acute renal failure (ARF). Therefore, this study was focused on investigating the possible protective effect of AG against GEN-induced nephrotoxicity in an in vivo rat model. We investigated the effects of AG on GEN-induced changes in renal tissue malondialdehyde (MDA) levels; nitric oxide (NO) generation; glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities; glutathione (GSH) content; serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Morphological changes in the kidney were also examined using light microscopy. GEN administration to control group rats increased renal MDA and NO levels but decreased GSH-Px, SOD, CAT activities and GSH content. AG administration with GEN injection resulted in significantly decreased MDA, NO generation and increased GSH-Px, SOD, CAT activities and GSH content when compared with GEN alone. Serum levels of Cr and BUN significantly increased as a result of nephrotoxicity. Also, AG significantly decreased Cr and BUN levels. Morphological changes in the kidney, including tubular necrosis, intracellular edema, glomerular and basement membrane alterations were evaluated qualitatively. Both biochemical findings and histopathological evidence showed that administration of AG reduced the GEN-induced kidney damage. We propose that AG acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN both at the biochemical and histological level.     

Effects of pioglitazone on hyperglycemia-induced alterations in antioxidative system in tissues of alloxan-treated diabetic animals.

Hyperglycemia not only generates reactive oxygen species but also attenuates antioxidant mechanisms creating a state of oxidative stress. Oxidative stress is thought to play a crucial role in pathogenesis of chronic diabetic complications. Pioglitazone is a new oral antidiabetic agent, a potent inhibitor of glycation and potent antioxidant. In the present study, normoglycemic and alloxan-induced diabetic rabbits were treated with pioglitazone (1 mg/kg daily) for 4 and 8 weeks. At the end, glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione (GSH) and protein carbonyl groups (PCG) were evaluated in homogenates of liver and kidney. Chronic hyperglycemia caused a marked increase in oxidative processes and some changes in activity of antioxidants. In liver, diabetic vs. control values (mean+/-S.E.M; P<0.05) for GSH-Px were 181.0+/-5.4 vs. 203.1+/-1.9 and 187.4+/-6.6 vs. 240.9+/-18.8mU/mg protein. Pioglitazone treatment for 8 weeks affected GSH-Px activity in diabetic liver (261.5+/-7.3 mU/mg protein). In diabetic kidney, GSSG-R activity (20.6+/-1.6 vs. 32.4+/-1.5 and 23.6+/-0.6 vs. 36.3+/-0.3 mU/mg protein) and GSH level (16.6+/-0.5 vs. 23.2+/-0.9 and 17.9+/-0.5 vs. 23.2+/-0.6 nmol/mg protein) were diminished, while PCG level (0.32+/-0.03 vs. 0.11+/-0.02 and 0.35+/-0.03 vs. 0.16+/-0.03 nmol/mg protein) was elevated. In diabetic kidney, pioglitazone restored to control values GSSG-R activity (34.4+/-1.4 and 30.6+/-0.1 mU/mg protein) as well as GSH (25.5+/-1.2 and 21.6+/-0.5 nmol/mg protein) and PCG (0.16+/-0.01 and 0.19+/-0.02 nmol/mg protein) levels. The present study showed that pioglitazone reduced to some extent the oxidative stress enhanced by chronic hyperglycemia.     

Antioxidant capacity and nitric oxide in patients with hepatic cirrhosis

This study investigated the relationship between the antioxidant capacity of blood and the serum level of nitric oxide (NO) in patients with hepatic cirrhosis. The study included 20 patients with compensated cirrhosis (group I), 30 with decompensated cirrhosis (group II), and 30 healthy controls (group III). The serum levels of NO, albumin, bilirubin, and uric acid, and the erythrocyte activity of superoxide dismutase (SOD) were measured in all groups. The mean erythrocyte SOD activity (5.94 +/- 3.21 U/mg protein) and serum NO level (25.19 +/- 8.15 micromol/L) in group I were similar to those of controls (6.86 +/- 2.47 U/mg protein and 21.67 +/- 6.51 micromol/L, respectively). However, erythrocyte SOD activity in group II was significantly lower than in groups I and III and mean serum NO level was significantly higher in group II than in groups I and III. In regard to non-enzymatic antioxidants, the mean serum albumin level was lower and the mean serum total bilirubin level was higher in group II than in groups I and III. As expected, group I had higher mean serum total bilirubin level than the control group. Correlation analysis showed that erythrocyte SOD activity in cirrhotic patients was negatively correlated with their serum levels of NO. These results suggest that disturbances of antioxidative mechanisms may diminish hepatic resistance to oxidative stress, thereby contributing to the development of fibrogenesis.     

Methionine-supplemented diet augments hepatotoxicity and prooxidant status in chronically ethanol-treated rats

The purpose of this study was to investigate whether high methionine (HM) diet may influence the development of ethanol-induced hepatotoxicity and prooxidant–antioxidant balance in the liver. Rats received drinking water containing ethanol (20% v/v) and/or methionine supplemented diet (2% w/w) for 75 days. Although prooxidant–antioxidant balance did not change in the liver of rats in HM group, ethanol treatment was observed to increase plasma transaminase activities, and malondialdehyde (MDA) and protein carbonyl (PC) levels, but not glutathione (GSH), vitamin E and vitamin C levels, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in the liver of rats as compared to controls. However, ethanol plus HM diet caused further increases in plasma transaminase activities and hepatic MDA and PC levels. In addition, SOD, GSH-Px and GST activities were observed to decrease, but GSH, vitamin E and vitamin C levels remained unchanged in the liver as compared to ethanol, HM and control groups. Our results show that HM diet may augment hepatotoxicity and oxidative stress in the liver of chronically ethanol-treated rats.     

Serum levels of bcl-2 and cellular oxidative stress in patients with viral hepatitis

PURPOSE: This study was conducted to investigate the presence of bcl-2 protein in the serum of patients with viral hepatitis and to find out if there is any correlation between bcl-2 protein levels and cellular oxidative stress in the pathogenesis of viral hepatitis. METHODS: This study was carried out on 130 patients with viral hepatitis, 70 with chronic hepatitis, 30 with liver cirrhosis and 30 with hepatocellular carcinoma (HCC) in addition to 20 healthy persons as the control. Serum bcl-2 protein was estimated by enzyme-linked immunosorbent assay, serum malondialdehyde (MDA), nitric oxide (NO) and antioxidant enzymes (GSH, GSH-px, GR and SOD) were measured using spectrophotometric analysis. RESULTS: bcl-2 protein level was significantly elevated in the serum of HCC, cirrhosis and chronic hepatitis groups as compared to control group. There were significant positive correlations between higher bcl-2 protein level and viral hepatitis markers (HBsAg, anti-HCV antibodies) in HCC and cirrhotic patients as compared to chronic hepatitis group. An increase in oxidative stress markers (MDA, NO) and a decrease in antioxidant enzyme activities (SOD, GSH and GSH-px) were observed. However, there was a negative correlation between bcl-2 levels and GR in all studied patient groups. CONCLUSIONS: The release of oxidative free radicals, deficiency in antioxidant enzymes and the expression of bcl-2 protein might play a role in the pathogenesis of viral hepatitis. The ability to measure bcl-2 protein in the serum could be useful as a prognostic marker of cancer patients.     

Alterations in the erythrocyte antioxidant system of blood stored in blood bags

In the present study, we measured the concentrations of reduced glutathione (GSH) and malonyldialdehyde (MDA) and the activities of glutathione peroxidase (GSH-Px), glutathione S-transferase (GSH-S-T), superoxide dismutase (SOD), catalase (CAT) and glucose-6-phosphate dehydrogenase (G-6-PD) in erythrocytes obtained freshly from adult male donors which was preserved with CPDA-1 anticoagulant (citrate,phosphate, dextrose, adenine) on different days of storage. At the end of the study, storage-associated alterations in antioxidant activities were noted and discussed. GSH, GSH-Px, GSH-S-T, SOD, CAT and G-6-PD activities decreased, but erythrocyte MDA levels, as anindex of lipid peroxidation, increased during the storage period. According to our results, glutathione-dependent antioxidant systems in erythrocytes might be depleted during long storage in blood bags.     

Overloaded training increases exercise-induced oxidative stress and damage.

We hypothesized that overloaded training (OT) in triathlon would induce oxidative stress and damage on muscle and DNA. Nine male triathletes and 6 male sedentary subjects participated in this study. Before and after a 4-week OT, triathletes exercised for a duathlon. Blood ratio of reduced vs. oxidized glutathione (GSH/GSSG), plasma thiobarbituric acid reactive substances (TBARS), leukocyte DNA damage, creatine kinase (CK), and CK-MB mass in plasma, erythrocyte superoxide dismutase (SOD) activity, erythrocyte and plasma glutathione peroxidase (GSH-Px) activities, and plasma total antioxidant status (TAS) were measured before and after OT in pre- and postexercise situations. Triathletes were overloaded in response to OT. In rest conditions, OT induced plasma GSH-Px activity increase and plasma TAS decrease (both p < 0.05). In exercise conditions, OT resulted in higher exercise-induced variations of blood GSH/GSSG ratio, TBARS level (both p < 0.05), and CK-MB mass (p < 0.01) in plasma; and decreased TAS response (p < 0.05). OT could compromise the antioxidant defense mechanism with respect to exercise-induced response. The resulting increased exercise-induced oxidative stress and further cellular susceptibility to damage needs more study.     

The effects of hormone replacement therapy on lipid peroxidation and antioxidant status

OBJECTIVE: A number of studies have consistently shown a lower cardiovascular risk in women who received postmenopausal hormone replacement therapy (HRT). The aim of our study was to examine the effects of HRT on lipid peroxidation and antioxidant status, which were likely to be involved in the pathophysiology of atherosclerosis. METHODS: We measured erythrocyte and plasma thiobarbituric acid reactive substances (TBARS) levels as expression of lipid peroxidation-end product malondialdehyde, and also erythrocyte reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity as indicators of the antioxidant status of the 35 postmenopausal women with HRT (mean age: 51.81 +/- 4.57 yr; body mass index (BMI): 26.56 +/- 3.78 kg/m(2)) and 35 postmenopausal women without HRT (mean age: 47.50 +/- 3.64; BMI: 27.42 +/-3.43 kg/m2). RESULTS: In the group with HRT, erythrocyte and plasma TBARS levels were significantly lower than in the group without HRT (P < 0.003 and P < 0.001, respectively). Erythrocyte GSH level and GSH-Px activity was found to be increased significantly in the group with HRT in comparison with the group without HRT (P < 0.001 and P < 0.001, respectively). There was not any correlation between the erythrocyte and plasma TBARS and erythrocyte GSH levels and GSH-Px activity with duration of HRT (mean 3.5+/-1.3 yr). CONCLUSION: Our results show that HRT is beneficial in the protection against oxidative damage and can prevent atherosclerotic complications.     

木材锯末与谷壳烟雾致豚鼠肺部炎性反应和氧化-抗氧化失衡

目的 探讨木材锯末和谷壳烟雾致豚鼠肺部的异常炎性反应及氧化损伤作用.方法 20只白化豚鼠随机分为两组,每组10只.实验组每天暴露于木材锯末和谷壳燃烧所产生的烟雾中两次,每次30 min,共21 d;对照组暴露于新鲜空气.3周后进行肺组织病理检测,并检测肺组织匀浆中的谷胱甘肽过氧化物酶(GSH-PX)、还原型谷胱甘肽(GSH)、丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、总抗氧化能力及肺泡灌洗液(BALF)中的MDA、SOD、总抗氧化能力、白细胞介素8(IL-8)、IL-6、细胞问黏附分子1(ICAM-1)的活力或含量.结果 与对照组豚鼠比较,实验组肺实质、小动脉及支气管炎性细胞浸润明显增多;肺泡面积比例及平均肺泡面积明显增大;单位而积肺泡数明显减少[(134.11±18.22)个/视野比(178.76±21.72)个/视野,P<0.01];肺小动脉及支气管平滑肌层显著增厚.肺组织匀浆中SOD、GSH-PX、GSH、CAT、总抗氧化能力的活力或含量降低[(225.55±12.52)U/mg比(296.57±13.46)U/mg,(23.60±1.85)mg/g比(34.38±1.85)mg/g,(119.67±9.61)mg/g比(134.73±8.07)mg/g,(7.10±0.21)U/mg比(9.20±0.24)U/mg,(0.89±0.10)U/mg比(1.27±0.15)U/mg,P均<0.01];MDA的含苗显著升高[(3.05±0.38)U/mg比(2.09±0.17)U/mg,P<0.01].BALF中,SOD、总抗氧化能力的活力显著降低;MDA的含量显著升高;BALF中IL-6、IL-8、ICAM-1浓度增高.结论 木材锯末与谷壳烟雾可导敛豚鼠肺组织及气道氧化-抗氧化失衡,引起氧化损伤.     

Effect of binge ethanol treatment on prooxidant-antioxidant balance in rat heart tissue

Binge drinking of alcohol is known to cause cardiac dysfunction in some drinkers. This study was designed to examine the effect of ethanol on rat heart tissue with an experimental model mimicking human binge drinking. Female Sprague-Dawley rats were given ethanol diluted with normal saline (40%, v:v) by gavage at the dose of 5.0g/kg every 12h for 3 doses as total. Serum activities of lactate dehydrogenase (LDH), creatine phosphokinase (CK) and aspartate transaminase (AST) were determined. Endogenous lipid peroxidation was assessed by measuring the levels of malondialdehyde (MDA) in heart homogenates. In vitro susceptibility of tissues to oxidative stress was assessed by using two different media. Tissue glutathione (GSH) and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. All serum enzymatic activities were found markedly elevated in ethanol group. Binge ethanol administration significantly enhanced endogenous lipid peroxidation and caused an enhanced in vitro susceptibility to lipid peroxidation. Levels of reduced GSH and GSH-Px and GST activities were found unchanged as compared to controls. SOD activity was found significantly increased. As a conclusion, binge ethanol consumption which was applied to rats to investigate acute tissue injury, appeared to confirm the generation of oxidative stress in rat hearts.     

In vivo effect of celecoxib and tenoxicam on oxidant/ anti-oxidant status of patients with knee osteoarthritis

The aim of this study was to compare the in vivo effects on free radical metabolism of 2 non-steroidal anti-inflammatory drugs (NSAIDs): tenoxicam, an oxicam preferentially cyclooxygenase-1 (COX-1) inhibitor, and celecoxib, a sulfonamide selective COX-2 inhibitor. The serum levels of oxidative stress-related enzymes (ie, xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)), of a lipid peroxidation marker (malondialdehyde (MDA)), and of nitric oxide (NO) in patients with knee osteoarthritis were studied at baseline and after a 4-wk course of treatment with celecoxib (n = 11) and tenoxicam (n = 12). Celecoxib-treated patients had significant decrease in nitrite levels (p = 0.043), whereas SOD, XO, GSH-Px enzyme activities, and MDA levels did not change significantly compared to baseline. Tenoxicam-treated patients had significant decrease in nitrite levels (p = 0.036) and XO activity (p = 0.01), but their SOD, GSH-Px enzyme activities, and MDA levels were unchanged from baseline. There was significant correlation between the patients' (n = 23) Western Ontario and McMaster Universities (WOMAC) LK3.0 Osteoarthritis Index, WOMAC-pain scores, and MDA levels (r = 0.50, p = 0.014) and the patients' WOMAC-stiffness scores and XO enzyme activity (r = 0.46, p = 0.027) at baseline. Significant improvement was found in pain-VAS, patients' global assessment, and WOMAC pain, stiffness, and physical function scores in celecoxib and tenoxicam-treated groups. In summary, our study revealed that tenoxicam may have antioxidant effects, and that celecoxib and tenoxicam may reduce nitrite levels, indicating an alteration of NO pathways.     

Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver

Endotoxemia-induced hepatotoxicity is characterized by disturbed intracellular redox balance, excessive reactive oxygen species (ROS) generation inducing DNA, proteins and membrane lipid damages. In the present study, the protective effects of montelukast (MNT) against Escherichia coli lipopolysaccharides (LPS)-induced oxidative stress were investigated in rat liver. LPS (10 mg/kg, i.p.) was injected and the animals were sacrificed 6 h after LPS challenge. MNT (10 mg/kg) was administered orally for seven successive days before endotoxemia induction. Blood samples were withdrawn for assessing the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and levels of serum total bilirubin, total protein, tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β). Livers were dissected out and used for histological examination or stored for the determination of malondialdehyde (MDA), protein carbonyl content (PCC), reduced glutathione (GSH) levels, enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO). Sepsis significantly increased ALT, AST, ALP, LDH, total bilirubin, TNF-α and IL-1β, MPO, MDA and PCC levels and decreased total protein, GSH and enzymatic antioxidants (CAT, SOD and GSH-Px). MNT decreased the markers of liver injury (AST, ALT, ALP, LDH, and total bilirubin), inflammatory biomarkers (TNF-alpha, IL-1β), MDA, PCC and MPO after LPS challenge. In conclusion, MNT abrogates LPS-induced markers of liver injury and suppresses the release of inflammatory and oxidative stress markers via its antioxidant properties and enhancement enzymatic antioxidant activities.     

中华眼镜蛇毒C组分对荷人胶质细胞瘤株U-251裸鼠血清抗氧化酶活性的影响

目的探讨中华眼镜蛇毒C组分对荷人胶质细胞瘤株U-251裸鼠血清抗氧化酶活性的影响。方法取荷人胶质细胞瘤株U-251的Balb/c裸鼠,经腹腔注射低、中、高浓度的FCNNAV1mg/L、5mg/L、10mg/L,采用比色法检测裸鼠血中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-PX)活性。结果荷人胶质细胞瘤株U-251裸鼠血清SOD、GSH-PX、CAT活性显著高于正常裸鼠组(P<0.05),MDA含量显著低于正常裸鼠组(P<0.05)。结论中华眼镜蛇毒C组分的抑瘤作用可能与其提高荷瘤鼠血血清抗氧化酶活性的影响有关。     

Potential hepatoprotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas

The aim of this study was to investigate the potential protective role of fullerenol C60(OH)24 on doxorubicin-induced liver toxicity using in vivo (female Sprague-Dawley rats) and in vitro (human hepatocellular carcinoma - HepG2; colorectal adenocarcinoma cell lines - Caco-2) approaches. The first (healthy control) and second (control with chemically induced mammary carcinomas) group received saline only. The third, fourth and fifth group (all with breast cancer) were injected (i.p.) with a single dose of doxorubicin (8mg/kg), doxorubicin/fullerenol (100mg/kg of fullerenol 30min before administration of 8mg/kg doxorubicin) and fullerenol (100mg/kg), respectively. Two days after treatment, the rats were sacrificed. Results showed that treatment with doxorubicin alone caused significant changes in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), as well as in the levels of malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) in the liver tissue. These effects were significantly reduced for all investigated parameters by pre-treatment with fullerenol but not for the MDA and GSH level. The HepG2 and Caco-2 cell lines were continuously treated with fullerenol for 12h, 24h, 48h and 96h at concentrations of 10microg/mL and 44microg/mL. With the aim of evaluating the modulating activity of fullerenol on doxorubicin-induced hepatotoxicity, the cell lines were simultaneously treated with doxorubicin (1microm; 5microm) and fullerenol (10microg/mL; 44microg/mL) in different combinations. When the cells are treated with 5microm doxorubicin along with the fullerenol, we can see a significant improvement of the cell capability during the entire time-line. We can conclude that fullerenol has cytotoxic effects on HepG2 by itself, but when the oxidative stress is too high the cytotoxic effects of fullerenol are overcome by its protective role as a strong antioxidant compound.     

Disturbance of pro-oxidative/antioxidative balance in allogeneic peripheral blood stem cell transplantation

High dose chemotherapy causes increased free radical formation and depletion of tissue antioxidants. Whether allogeneic hematopoietic stem cell transplantation (HSCT) has an effect on oxidative stress is uncertain. The aims of the study were to determine the effect of allogeneic HSCT on plasma concentrations of antioxidants and oxidative stress biomarkers, and to investigate their relationships with graft-versus-host disease (GVHD), conditioning regimens, and transplant-related mortality (TRM) in patients with hematological malignancies. Patients (n=25) undergoing allogeneic HSCT from HLA-matched sibling donors were enrolled in the study. Plasma oxidant and antioxidant status were measured at day -1 before transplantation and 30 days after HSCT. In both myeloablative (n=14) and non-myeloablative (n=11) transplant groups, the mean levels of plasma malondialdehyde (MDA) and nitric oxide (NO) increased after allogeneic HSCT (p <0.01), whereas superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities decreased compared with baseline values (p <0.01). No significant relationships were found between either the pretransplant or post-transplant mean levels of the oxidative stress parameters and the existence of graft-versus-host disease (GVHD), the type of conditioning regimen, or transplant related mortality (TRM). This study documents a significant disturbance of pro-oxidative/antioxidative balance in the plasma of patients undergoing allogeneic HSCT regardless of the intensity of the conditioning regimen.     

Not Only Melatonin but also Caffeic Acid Phenethyl Ester Protects Kidneys against Aging-related Oxidative Damage in Sprague Dawley Rats

Microscopic features and antioxidant status of kidneys of young, old, and caffeic acid phenethyl ester (CAPE) and melatonin administered old Sprague Dawley rats were evaluated. Aging-related tubular and glomerular changes were evident. The most prominent tubular alterations were massive vacuole formation, mitochondrial degeneration, and lysosome accumulation. Mean tissue malondialdehyde (MDA) level was increased, mean tissue superoxide dismutase (SOD), catalase (CAT) (p < .001), and glutathione peroxidase (GPx) activities (p < .05), and total glutathione (GSH) level were decreased in old animals. Melatonin significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .001), CAT, and GPx activities (p < .05), and GSH levels (p < .005) in old animals. CAPE also significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .05), CAT (p < .005), GPx activities, and GSH levels (p < .001) in old rats. Mean tissue MDA levels of melatonin and CAPE-administered rats were even lower than those of young rats (p < .05). In conclusion, tubular and glomerular structures and tissue antioxidant enzyme activities were very well preserved in CAPE and melatonin-administered rats.     

Systemic oxidative and antioxidative status in Chinese patients with asthma

BACKGROUND: Patients with asthma generate an increased amount of reactive oxygen species from peripheral blood cells. Reactive oxygen species produce many of the pathophysiologic changes associated with asthma and may contribute to its pathogenesis. OBJECTIVE: We investigated changes in antioxidant enzyme activities and oxidized glutathione (glutathione disulfide; GSSG) levels in erythrocytes from a group of healthy control Chinese subjects (n=135) and patients with asthma (n=106). METHODS: Baseline pulmonary function was measured for all subjects. Antioxidant status was evaluated by measuring erythrocyte superoxide dismutase, catalase, and glutathione peroxidase activities. Oxidative stress was also measured in terms of GSSG in erythrocytes with a kinetic microassay. RESULTS: Patients with asthma had significantly increased erythrocyte superoxide dismutase and catalase activities compared with controls (61.10 +/- 1.30 U/g hemoglobin [Hb] vs 55.51 +/- 1.82 U/g Hb [P=.018] and 0.0637 +/- 0.0021 U/g Hb vs 0.0257 +/- 0.0120 U/g Hb [P <.001] for the asthma and control groups, respectively). Conversely, erythrocyte glutathione peroxidase activity decreased (44.21 +/- 1.33 mU/g Hb vs 50.07 +/- 1.39 mU/g Hb for the asthma and control groups, respectively; P=.003). Patients with asthma also had significantly higher GSSG levels in erythrocyte hemolysates compared with controls (167.40 +/- 2.93 micromol/L vs 44.98 +/- 0.44 micromol/L for the asthma and control groups, respectively; P <.001), indicating increased oxidative stress. CONCLUSIONS: Asthma is accompanied by an alteration in systemic antioxidant status due to possible oxidative stress in this disease.     

Hepatic glutathione mediated antioxidant system in ethanol treated rats: Decline with age.

Alcoholism is a pervasive problem. The aim of the present study was to clarify the effect of ethanol on the hepatic glutathione antioxidant system in young and elderly rats. Male albino Wistar rats of two age groups (3 months and 18 months old) were divided into two experimental groups. The first group of untreated rats served as controls (C; young n=6 and old n=6) and second group received ethanol (Et; young n=6 and old n=6) 2g of ethanol/kg b.w. for 2 months. After the completion of last treatment glutathione (GSH) and antioxidant enzymes glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST) were determined. All these parameters including GST were remarkably decreased in the liver with advancing of age. The ethanol treatment decreased GSH, GSH-Px and GR, whereas, GST was increased in both age groups. The decrease of hepatic antioxidant status with ethanol and aging may be due to over production of free radicals. The changes of parameters studied were greater in the older than in the young rats. In conclusion, ethanol stress exhibited age dependent response on glutathione mediated antioxidant system in the liver.