JOURNAL OF FOOD PROCESSING AND PRESERVATION, Issue 3 2001
H. ZIELINSKI
Reduced and oxidized glutathione was assayed in wheat, barley, rye, oats and buckwheat before and after extrusion cooking. The results obtained indicate that GSH/GSSG ratio was decreased from 1.91 and 10.72 for raw oat and buckwheat grains to the 1.13, 1.01, 1.10 and 4.72, 3.89, 3.89 for extruded material, respectively, in temperature used of 120, 160 and 200C. These results indicate that the oxidative stress is least developed during extrusion cooking of oat and buckwheat grains. Wheat and barley grains were more prone to oxidative damage, and the observed decrease of the ratio ranged from 6.84 and 4.89 (wheat cv. Almari and barley cv. Mobek, raw material) to the 1.89 and 2.07 (after extrusion cooking at 200C, respectively). No significance differences were found between two cultivars of wheat and barley being used in the experiment. The most decreased ratio up to five times was found in rye grain extrudates. The extrusion performed under barrel temperature profile of 80,100,120,120,120C caused significant decrease in GSH content when compared to raw material. The next higher barrel temperature profiles of 100,130,160,160,120C and 120,160,200,200,120C led to further GSH decrease in extruded wheat grains. In contrast, the two high temperature profiles did not [source]

INTRAPERITONEAL GLYCEROL INDUCES OXIDATIVE STRESS IN RAT KIDNEY

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2008
Elenara Rieger
SUMMARY 1Glycerol has been used for the treatment of intracranial hypertension, cerebral oedema and glaucoma. Experimentally, intramuscular administration of hypertonic glycerol solution is used to produce acute renal failure. In this model, glycerol causes rhabdomyolysis and myoglobinuria, resulting in the development of renal injury. The pathogenesis is thought to involve vascular congestion, the formation of casts and oxidative stress. However, the effect of glycerol itself independent of rhabdomyolysis has not been investigated. Therefore, the aim of the present study was to investigate the effects of i.p. glycerol on some biochemical and oxidative stress parameters in the kidney of young rats. 2Rats received 10 mL/kg, i.p., hypertonic glycerol solution (50% v/v) or saline (NaCl 0.85 g%) followed by 24 h water deprivation. Twenty-four hours after the administration of glycerol, rats were killed. Creatinine levels and the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) were determined in the plasma. In addition, CK, pyruvate kinase and LDH activity and oxidative stress parameters (free radical formation, lipid peroxidation and protein carbonylation) were measured in renal tissue. 3Glycerol did not alter plasma CK activity and increased plasma creatinine levels, suggesting renal insufficiency and the absence of rhabdomyolysis. Renal CK and pyruvate kinase activity was decreased, suggesting diminution of energy homeostasis in the kidney. Plasma and renal LDH activity was decreased, whereas the formation of free radicals, lipid peroxidation and protein carbonylation were increased, suggesting oxidative stress. 4These results are similar to those described after the intramuscular administration of glycerol. Therefore, it is possible that glycerol may provoke renal lesions by mechanisms other than those induced by rhabdomyolysis. [source]

OXIDATIVE STRESS IS AN IMPORTANT COMPONENT OF AIRWAY INFLAMMATION IN MICE EXPOSED TO CIGARETTE SMOKE OR LIPOPOLYSACCHARIDE

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2008
Vincent Lagente
SUMMARY 1It was proposed previously that oxidative stress is a main component of the inflammatory process in chronic obstructive pulmonary disease (COPD). Thus, in the present study, we investigated the inflammatory response in mice deficient for the p47phox subunit of NADPH oxidase (p47 KO) exposed to cigarette smoke (CS). 2Exposure of mice to CS elicited an increase in the number of macrophages and neutrophils and levels of interleukin (IL)-6, keratinocyte-derived chemokine (KC/CXCL1) and monocyte chemoattractant protein-1 (MCP1/CCL2) in bronchoalveolar lavage fluid (BALF), which were lower in p47 KO mice compared with control mice. In contrast, 24 h after lipopolysaccharide (LPS) exposure, the number of macrophages and neutrophils, as well as KC/CXCL1 levels, in BALF was significantly greater in p47 KO mice compared with control mice. 3The present study has shown that airway inflammation is decreased in p47 KO mice after exposure to CS, but not LPS, suggesting that oxidative stress is involved in the pathogenesis of airway inflammation associated with COPD. [source]

INVESTIGATION OF THE MICROCIRCULATION AND THE STATE OF OXIDATIVE STRESS IN THE RAT AFTER SCORPION ENVENOMATION

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2007
Z Sahnoun
SUMMARY 1Severe cases of scorpion envenomation (SE) generally show both respiratory and cardiocirculatory dysfunction. However, the pathophysiology of SE remains controversial. In the present study, we tried to explain the pathophysiology of the haemodynamic perturbations and cardiac failure in rats poisoned by the venom of Buthus occitanus tunetanus through a histomorphometric study of myocardial and muscular skeletal microcirculation and analysis of the oxidative stress state in order to evaluate the implication of the inflammatory process in the pathogenesis of SE. 2Experiments were performed on 96 rats divided into 16 groups (n = 6 in each group). Two groups were used to determine the optimum conditions of venom administration and times when to measure haemodynamic parameters. The B. occitanus tunetanus venom was administered at a dose of 800 µg/kg and tissues were removed 5 and 20 min after envenomation. Six groups were used for histomorphometric study: two control groups, two poisoned groups an two melatonin-pretreated and poisoned groups. The histomorphometric study was performed on isolated hearts and skeletal muscles. The final eight groups of rats (two control groups, two envenomated groups, two control groups pretreated with melatonin and two groups pretreated and envenomated) were used to investigate the state of tissue oxidative stress during SE and to evaluate the anti-oxidant effect of melatonin on rats poisoned with B. occitanus tunetanus venom. This study was based on the determination of tissue malondialdehyde in isolated organs as an indicator of thiobarbituric acid-reactive substances (TBARS). Melatonin was injected at a dose of 5 mg/kg, i.v., 15 min before the administration of serum or venom. Data were compared using analysis of variance and Tukey's test for multiple pair-wise comparisons. 3Five minutes after venom injection, a significant reduction in the mean relative volume of venules and arterioles in the heart and skeletal muscles of poisoned rats was noted. Twenty minutes after venom injection, these volumes were significantly increased in the heart and skeletal muscles of poisoned rats. Pretreatment of envenomated rats with melatonin resulted in a significant decrease in the mean relative volume of the venules and arterioles in the heart and skeletal muscles 5 and 20 min after venom injection compared with untreated envenomated rats. Investigation of the oxidative stress state showed a highly significant increase in TBARS in poisoned rats compared with control groups 5 and 20 min after venom injection. Melatonin pretreatment of rats poisoned with B. occitanus tunetanus venom resulted in an important and highly significant reduction of TBARS compared with untreated envenomated rats. 4It appears from the results of the present study that administration of B. occitanus tunetanus venom engendered an excessive myocardial and skeletal muscular vasoconstriction attributed to massive catecholamine release followed by arteriolar and venular vasodilatation. This venous stasis at the muscular microcirculation could be due to myocardiac failure. However, the concomitant presence of arteriolar vasodilatation suggests an inflammatory process in the pathophysiology of SE. This process was suggested by the genesis of a state of oxidative stress in relation to the important lipoperoxidation, which was inhibited by administration of the anti-oxidant melatonin. Thus, melatonin pretreatment seemed to accentuate the first phase of vascular reactivity in envenomed rats and inhibit the second vasodilator phase observed 20 min after administration of the venom. [source]

Unraveling the Role of Mitochondria During Oxidative Stress in Plants

IUBMB LIFE, Issue 4 2001
Harvey Millar
Abstract The sedentary habit of plants means that they must stand and fight environmental stresses that their mobile animal cousins can avoid. A range of these abiotic stresses initiate the production in plant cells of reactive oxygen and nitrogen species that ultimately lead to oxidative damage affecting the yield and quality of plant products. A complex network of enzyme systems, producing and quenching these reactive species operate in different organelles. It is the integration of these compartmented defense systems that coordinates an effective response to the various stresses. Future attempts to improve plant growth or yield must consider the complexity of inter-organelle signaling and protein targeting if they are to be successful in producing plants with resistance to a broad range of stresses. Here we highlight the role of pre-oxidant, anti-oxidant, and post-oxidant defense systems in plant mitochondria and the potential role of proteins targeted to both mitochondria and chloroplasts, in an integrated defense against oxidative damage in plants. [source]

An Overview of Oxidative Stress

IUBMB LIFE, Issue 4-5 2000
Kelvin J. A. Davies
First page of article [source]

Mitochondrial Oxidative Stress Plays a Key Role in Aging and Apoptosis

IUBMB LIFE, Issue 5 2000
Juan Sastre
Abstract Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitochondrial production of hydroperoxide and the maximum life span of species. An important change in mitochondrial lipid composition is the age-related decrease found in cardiolipin content. The concurrent enhancement of lipid peroxidation and oxidative modification of proteins in mitochondria further increases mutations and oxidative damage to mitochondrial DNA (mtDNA) in the aging process. The respiratory enzymes containing the defective mtDNA-encoded protein subunits may increase the production of reactive oxygen species, which in turn would aggravate the oxidative damage to mitochondria. Moreover, superoxide radicals produced during mitochondrial respiration react with nitric oxide inside mitochondria to yield damaging peroxynitrite. Treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E, or the Ginkgo biloba extract EGb 761, protects against the ageassociated oxidative damage to mtDNA and the oxidation of mitochondrial glutathione. Moreover, the EGb 761 extract also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver. [source]

High Oxidative Stress Is Correlated with Frailty in Elderly Chinese

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9 2009
I-Chien Wu MD
OBJECTIVES: To evaluate the relationship between oxidative stress and frailty in elderly people. DESIGN: Cross-sectional study. SETTING: Community and hospital-based outpatient clinic. PARTICIPANTS: Ninety participants aged 65 and older. MEASUREMENTS: Frailty status was determined according to the presence of weak handgrip strength, weight loss, slow walking speed, exhaustion, and low activity level and was classified as frail (,3 criteria), prefrail (1 or 2 criteria), or robust (0 criteria). An oxidative stress marker (serum 8-hydroxy-2,-deoxyguanosine, 8-OHdG), metabolic markers (body mass index, waist,hip ratio, serum lipids, glucose, and albumin), an inflammatory marker (serum high-sensitivity C-reactive protein, hs-CRP), demographic information, and comorbidities (diabetes mellitus, hypertension, congestive heart failure, osteoarthritis, overweight or obesity, impaired fasting plasma glucose, renal insufficiency, and depression) were assessed. RESULTS: Of the 90 participants, 21 (23.3%) were frail, 56 (62.2%) were prefrail, and 13 (14.4%) were robust. Frail subjects had higher median (range) serum 8-OHdG (2.5 ng/mL (1.5,6.2 ng/mL) vs 2.3 ng/mL (0.5,8.1 ng/mL) and 1.0 ng/mL (0.5,5.3 ng/mL)) and serum hs-CRP (2.5 mg/L (0.3,32.1 mg/L) vs 1.8 mg/L (0.3,50.5 mg/L) and 1.7 mg/L (0.3,4.0 mg/L)) levels, lower mean±standard deviation serum albumin levels (4.1±0.4 g/dL vs 4.4±0.4 g/dL and 4.6±0.2 g/dL) and higher mean waist,hip ratios (0.96±0.11 vs 0.91±0.07 and 0.89±0.05)) than prefrail and robust subjects, respectively (P<.05 for all). In multivariable regression analysis, high serum 8-OHdG level was still significantly associated with frailty after adjusting for age, smoking status, comorbidities, waist,hip ratio, serum albumin level, and hs-CRP level. CONCLUSION: High oxidative stress, characterized by high serum 8-OHdG level, was independently associated with frailty in the selected sample of elderly Chinese. [source]

Exercise-Induced Oxidative Stress in Older Adults as a Function of Habitual Activity Level

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2002
Erwin P. Meijer PhD
First page of article [source]

Amelioration of Cadmium-Induced Oxidative Stress, Impairment in Lipids and Plasma Lipoproteins by the Combined Treatment with Quercetin and ,-Tocopherol in Rats

JOURNAL OF FOOD SCIENCE, Issue 7 2010
S. Milton Prabu
Abstract:, Cadmium (Cd) exposure results in numerous pathological consequences including oxidative stress and dyslipidemia. The present study was designed to investigate the efficacy of combined treatment with quercetin (QE) and ,-tocopherol (AT) against Cd-induced oxidative stress and alterations in lipids and lipoproteins in the plasma and liver of rats. Oral administration of Cd (5 mg/kg bw/d) for 4 wk has shown a significant (P < 0.05) increase in thiobarbituric acid reactive substances (TBARS), lipid hydro peroxides (LOOH), total cholesterol, low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), free fatty acids (FFA), phospholipids (PL), triglycerides (TGs), and the activity of hydroxyl-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) in plasma with a significant (P > 0.05) reduction in the levels of reduced glutathione (GSH), high density lipoprotein cholesterol (HDL-C), and the activity of lecithin cholesterol acyl transferase (LCAT) in plasma. In addition, the levels of hepatic thiobarbituric acid reactive substances (TBARS), LOOH, conjugated dienes (CD), protein carbonyls (PC), and the activity of HMG-CoA reductase, levels of cholesterol, FFA, and TGs were significantly (P > 0.05) increased and the level of PL is significantly (P > 0.05) decreased along with the decreased activity of LCAT in the liver of Cd-treated rats. Oral supplementation with QE (50 mg/kg bw/d) and AT (50 mg/kg bw/d) for 4 wk in Cd intoxicated rats significantly (P > 0.05) has reduced the plasma levels of TBARS, LOOH, GSH, cholesterol, FFA, TGs, VLDL-C, LDL-C, and the activity of HMG-CoA and significantly (P > 0.05) has increased the activity of LCAT and the plasma levels of HDL-C. The oral supplementation also significantly (P > 0.05) has reduced the hepatic oxidative stress markers, cholesterol, TGs, FFA, and significantly (P > 0.05) has increased the LCAT activity and the PL in liver. Our results indicate that the combined treatment with QE and AT has normalized all the previously mentioned biochemical parameters in Cd-intoxicated rats than the individual treatments. The combined treatment has provided remarkable protection against Cd-induced oxidative stress and alterations in lipid metabolism and, thereby, reduced the Cd-mediated cardiovascular diseases. [source]

Oxidative Stress Following Traumatic Brain Injury in Rats

JOURNAL OF NEUROCHEMISTRY, Issue 5 2000
Detection of Free Radical Intermediates, Quantitation of Biomarkers
Abstract: Oxidative stress may contribute to many pathophysiologic changes that occur after traumatic brain injury. In the current study, contemporary methods of detecting oxidative stress were used in a rodent model of traumatic brain injury. The level of the stable product derived from peroxidation of arachidonyl residues in phospholipids, 8- epi -prostaglandin F2,, was increased at 6 and 24 h after traumatic brain injury. Furthermore, relative amounts of fluorescent end products of lipid peroxidation in brain extracts were increased at 6 and 24 h after trauma compared with sham-operated controls. The total antioxidant reserves of brain homogenates and water-soluble antioxidant reserves as well as tissue concentrations of ascorbate, GSH, and protein sulfhydryls were reduced after traumatic brain injury. A selective inhibitor of cyclooxygenase-2, SC 58125, prevented depletion of ascorbate and thiols, the two major water-soluble antioxidants in traumatized brain. Electron paramagnetic resonance (EPR) spectroscopy of rat cortex homogenates failed to detect any radical adducts with a spin trap, 5,5-dimethyl-1-pyrroline N -oxide, but did detect ascorbate radical signals. The ascorbate radical EPR signals increased in brain homogenates derived from traumatized brain samples compared with sham-operated controls. These results along with detailed model experiments in vitro indicate that ascorbate is a major antioxidant in brain and that the EPR assay of ascorbate radicals may be used to monitor production of free radicals in brain tissue after traumatic brain injury. [source]

Effect of Exogenous and Endogenous Antioxidants on 3-Nitropionic Acid-Inducedin vivo Oxidative Stress and Striatal Lesions

JOURNAL OF NEUROCHEMISTRY, Issue 4 2000
Insights into Huntington's Disease
Abstract: 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of complex II in the mitochondria. 3-NP toxicity has gained acceptance as an animal model of Huntington's disease (HD). In the present study, we confirmed that rats injected with 3-NP (20 mg/kg, i.p., daily for 4 days) exhibit increased oxidative stress in both striatum and cortical synaptosomes as well as lesions in the striatum. Synaptosomal membrane proteins from rats injected with 3-NP exhibited a decrease in W/S ratio, the relevant electron paramagnetic resonance (EPR) parameter used to determine levels of protein oxidation, and western blot analysis for protein carbonyls revealed direct evidence of increased synaptosomal protein oxidation. Treatment of rats with the brain-accessible free radical spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N -oxide (DEPMPO; 30 mg/kg, i.p., daily 2 h before 3-NP injection) or with N -acetylcysteine (NAC; 100 mg/kg, i.p., daily 2 h before 3-NP injection), a known glutathione precursor, before 3-NP treatments protects against oxidative damage induced by 3-NP as measured by EPR and western blot analysis for protein carbonyls. Furthermore, both DEMPMPO and NAC treatments before 3-NP administration significantly reduce striatal lesion volumes. These data suggest oxidative damage is a prerequisite for striatal lesion formation and that antioxidant treatment may be a useful therapeutic strategy against 3-NP neurotoxicity and perhaps against HD as well. [source]

Ethanol-Induced Oxidative Stress and Mitochondrial Dysfunction in Rat Placenta: Relevance to Pregnancy Loss

ALCOHOLISM, Issue 3 2010
Fusun Gundogan
Background:, Ethanol consumption during pregnancy increases the risk of early pregnancy loss and causes intrauterine growth restriction. We previously showed that chronic gestational exposure to ethanol impairs placentation, and that this effect is associated with inhibition of insulin and insulin growth factor signaling. Since ethanol also causes oxidative stress and DNA damage, we extended our investigations to assess the role of these pathological processes on placentation and placental gene expression. Methods:, Pregnant Long Evans rats were pair-fed liquid diets containing 0% or 24% ethanol by caloric content. Placentas harvested on gestation day 16 were used to examine DNA damage, lipid peroxidation, apoptosis, mitochondrial gene/protein and hormonal gene expression in relation to ethanol exposure. Results:, Gestational exposure to ethanol increased fetal resorption, and trophoblast apoptosis/necrosis, oxidative stress, DNA damage, and lipid peroxidation. These adverse effects of ethanol were associated with increased expression of pro-apoptotic (Bax and Bak) and reduced levels of the anti-apoptotic Bcl-2 protein. In addition, increased trophoblast apoptosis proneness was associated with p53-independent activation of p21, reduced mitochondrial gene and protein expression, and dysregulated expression of prolactin (PRL) family hormones that are required for implantation and pregnancy-related adaptations. Conclusions:, Chronic gestational exposure to ethanol increases fetal demise due to impaired survival and mitochondrial function, increased oxidative stress, DNA damage and lipid peroxidation, and dysregulated expression of prolactin family hormones in placental trophoblasts. [source]

Alcohol-Induced Endothelial Changes Are Associated With Oxidative Stress and Are Rapidly Reversed After Withdrawal

ALCOHOLISM, Issue 10 2005
Giorgio Soardo
Abstract: Background: Although heavy alcohol drinkers are at an increased risk of developing cardiovascular events, moderate alcohol intake is associated with reduced incidence of cardiovascular death. This paradox might reflect a dose-related effect of different alcohol intakes on endothelial function and this, in turn, might depend on changes in oxidative stress Methods: We tested the effects of alcohol withdrawal in heavy alcohol consumers and compared the plasma levels of endothelin-1, nitric oxide, plasminogen activator inhibitor-1, von Willebrand factor, malondialdehyde, and intracellular glutathione with those of alcoholics that did not modify their alcohol intake and teetotalers. In human endothelial cells that had been cultured for 2 weeks in the presence of different concentrations of ethanol, we assessed the same parameters after withdrawal of ethanol exposure Results: Alcohol increased the levels of endothelin-1, nitric oxide, and plasminogen activator inhibitor-1 and decreased the levels of von Willebrand factor both in vivo and in vitro. These changes were dose dependent, rapidly reversed after withdrawal of exposure, and associated with the presence of increased oxidative stress as indicated by increased levels of both malondialdehyde and intracellular glutathione. Blockade of oxidative stress by incubation of endothelial cells in the presence of oxidants' scavengers prevented the alcohol-induced functional modifications of the endothelium Conclusions: Alcohol affects endothelial function with an effect that is mediated by an activated oxidative stress and is rapidly reversed after withdrawal. Dose-related endothelial responses to different alcohol intakes might translate in either vascular protection or vascular damage. [source]

Decreased Proteasome Activity Is Associated With Increased Severity of Liver Pathology and Oxidative Stress in Experimental Alcoholic Liver Disease

ALCOHOLISM, Issue 8 2004
Terrence M. Donohue Jr
Background: Because of its role in degrading the bulk of intracellular proteins and eliminating damaged proteins, the proteasome is important in maintaining cell viability. Previously, we showed a 35,40% decrease in proteasome peptidase activity when ethanol was administered to rats by intragastric infusion. We hypothesized that this reduction was caused by ethanol-elicited oxidative stress, the degree of which varies depending on the method of ethanol administration. This study examined the relationship of proteasome activity and content with ethanol-induced oxidative stress and the degree of liver injury. Methods: Rats were given ethanol or isocaloric dextrose-containing liquid diets by intragastric infusion for 1 month. The diets contained medium-chain triglycerides (MCT), palm oil (PO), corn oil (CO), or fish oil (FO) as the principal source of fat. Results: Rats given ethanol and MCT exhibited no significant liver pathology, whereas cumulative pathology scores in ethanol-fed rats given PO, CO, or FO were 2.5, 5.4 and 7.0, respectively, indicating that ethanol and FO caused the greatest liver damage. The severity of liver pathology in the last three groups of animals correlated with levels of lipid peroxides and serum 8-isoprostanes. Alpha smooth muscle actin, an indicator of stellate cell activation, was increased relative to controls in the livers of all ethanol-fed rats except FO-fed animals, in which both control and ethanol-fed rats had similar levels of this protein. In livers of CO and FO ethanol-fed rats, proteasome chymotrypsin-like activity was decreased by 55,60%, but there was no quantitative alteration in 20S proteasome subunit content. In contrast, ethanol affected neither proteasome activity nor its content in MCT- and PO-treated animals. Conclusions: Our findings indicate that the severity of liver injury and ethanol-induced oxidative stress is associated with a reduction in proteasome catalysis. [source]

Oxidative Stress and Neutrophil Function in Cats with Chronic Renal Failure

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2010
R.F. Keegan
Background: Oxidative stress is an important component in the progression of chronic renal failure (CRF) and neutrophil function may be impaired by oxidative stress. Hypothesis: Cats with CRF have increased oxidative stress and decreased neutrophil function compared with control cats. Animals: Twenty cats with previously diagnosed renal failure were compared with 10 age-matched control cats. Methods: A biochemical profile, CBC, urinalysis, antioxidant capacity, superoxide dismutase (SOD) enzyme activity, reduced to oxidized glutathione ratio (GSH : GSSG), and neutrophil phagocytosis and oxidative burst were measured. Statistical comparisons (2-tailed t -test) were reported as mean ± standard deviation. Results: The CRF cats had significantly higher serum blood urea nitrogen, creatinine, and phosphorus concentrations than control cats, and significantly lower PCV and urine specific gravity than control cats. The GSH : GSSG ratio was significantly higher in the CRF group (177.6 ± 197, 61.7 ± 33; P < .02) whereas the antioxidant capacity was significantly less in the CRF group (0.56 ± 0.21, 0.81 ± 0.13 Trolox units; P < .005). SOD activity was the same in control and CRF cats. Neutrophil oxidative burst after Escherichia coli phagocytosis, measured as an increase in mean fluorescence intensity, was significantly higher in CRF cats than controls (732 ± 253, 524 ± 54; P < .05). Conclusions: The higher GSH : GSSG ratio and lower antioxidant capacity in CRF cats is consistent with activation of antioxidant defense mechanisms. It remains to be determined if supplementation with antioxidants such as SOD beyond the level of control cats would be of benefit in cats with CRF. [source]

Antioxidant Status and Biomarkers of Oxidative Stress in Dogs with Lymphoma

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2009
J.L. Winter
Background: Oxidative stress might play a role in carcinogenesis, as well as impacting morbidity and mortality of veterinary cancer patients. The purpose of this study was to evaluate antioxidant concentrations and biomarkers of oxidative stress in dogs with newly diagnosed lymphoma before treatment and once in remission, with comparison with healthy controls. Hypothesis: Dogs with lymphoma have increased oxidant and reduced antioxidant concentrations compared with healthy controls, and that these abnormalities normalize once remission is achieved. Animals: Seventeen dogs with lymphoma and 10 healthy controls. Methods: Prospective, observational study. Measures of oxidative stress [malondialdehyde and total isoprostanes (isoP)] and antioxidants [,-tocopherol, ,-tocopherol, oxygen radical absorbance capacity (ORAC), and glutathione peroxidase (GSHPx)] were assessed in dogs with newly diagnosed lymphoma before treatment compared with healthy control dogs. The same parameters were measured in the dogs with lymphoma on week 7 of the chemotherapy protocol when all dogs were in remission. Results: At baseline, dogs with lymphoma had significantly lower ,-tocopherol (P <.001) and ,-tocopherol (P= .003) but higher GSHPx (P= .05), ORAC (P= .001), and isoP (P < .001) compared with healthy controls. In the dogs with lymphoma, ,-tocopherol concentrations were higher (P= .005) and ascorbic acid were lower (P= .04) after treatment. Conclusions and Clinical Importance: Results suggest that dogs with lymphoma have alterations in oxidant and antioxidant concentrations and that the status of some of these biomarkers normalize after remission. Further studies are warranted to determine whether antioxidant interventions to correct these are beneficial in the treatment of canine lymphoma. [source]

Differential Effects of Oxidative Stress on Hepatic Endothelial and Kupffer Cell Eicosanoid Release in Response to Endothelin-1

MICROCIRCULATION, Issue 6 2006
AMEL KARAA
ABSTRACT Objective: The vasoconstrictor endothelin-1 can induce vasomodulators release like nitric oxide in the liver. Here the authors explored whether endothelin-1 can stimulate endothelial and Kupffer cells release of other vasomodulators under normal and stress conditions. Methods: Cells were cultured for 24 h and treated with H2O2 (25 ,M) for 6 h and subsequently with endothelin-1 (10 nM) for 10 min. Eicosanoid release was assessed in the media by enzyme immunoassay. Results: Endothelin-1 mediated cPLA2 phosphorylation and increased prostaglandin (PG) I2, PGE2 and thromboxane A2 (TXA2) release in endothelial cells while it only increased TXA2 in Kupffer cells. H2O2 significantly increased PGI2, PGE2 and TXA2 in endothelial cells through an upregulation of cyclooxygenase-2, thromboxane synthase A2, and phosphorylation of cPLA2. Endothelin-1-induced PGI2, PGE2, and TXA2 release in endothelial cells were inhibited by H2O2 correlating with the absence of further cPLA2 phosphorylation. In Kupffer cells, H2O2 only increased TXA2 synthesis and further endothelin-1 stimulation of TXA2 was possible through a higher increase in cPLA2. Conclusion: These results indicate that under normal conditions endothelial cells play a pivotal role in liver microcirculation regulation. Oxidative stress not only disrupts the basal balance of vasomodulators in the liver but also affects endothelin-1-induced effects in both Kupffer cells and endothelial cells. [source]

Inhibition of UVB-mediated Oxidative Stress and Markers of Photoaging in Immortalized HaCaT Keratinocytes by Pomegranate Polyphenol Extract POMx

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2007
Mohammad Abu Zaid
In recent years there has been an increase in use of botanicals with antioxidant properties as skin photoprotective agents. Pomegranate (Punica granatum L.) fruit possesses strong antioxidant and antiinflammatory properties. Recently, we have shown that pomegranate-derived products rich in anthocyanidins and ellagitannins inhibit UVB-mediated activation of nuclear factor kappa B and modulate UVA-mediated cell proliferation pathways in normal human epidermal keratinocytes. In this study, we evaluated the effect of polyphenol-rich pomegranate fruit extract (POMx) on UVB-induced oxidative stress and photoaging in human immortalized HaCaT keratinocytes. Our data show that pretreatment of HaCaT cells with POMx (10,40 ,g mL,1) inhibited UVB (15,30 mJ cm,2)-mediated (1) decrease in cell viability, (2) decrease in intracellular glutathione content and (3) increase in lipid peroxidation. Employing immunoblot analysis we found that pretreatment of HaCaT cells with POMx inhibited UVB-induced (1) upregulation of MMP-1, -2, -7 and -9, (2) decrease in TIMP-1, (3) phosphorylation of MAPKs and (iv) phosphorylation of c-jun, whereas no effect was observed on UVB-induced c-fos protein levels. These results suggest that POMx protects HaCaT cells against UVB-induced oxidative stress and markers of photoaging and could be a useful supplement in skin care products. [source]

Reduction of Oxidative Stress in Bovine Spermatozoa During Flow Cytometric Sorting

REPRODUCTION IN DOMESTIC ANIMALS, Issue 1 2007
P Klinc
Contents The goal of the study was to investigate the effect of antioxidant supplementation on the quality of frozen-thawed flow cytometrically sorted bull spermatozoa. Twelve ejaculates from two Holstein Friesian bulls were sorted according to the Beltsville Sperm Sexing Technology. Each ejaculate was divided into three parts and processed as (i) unsorted controls, (ii) according to a standard sorting protocol and (iii) in the presence of different antioxidants (S-AO). Cooling and freezing of the samples were performed in the same way for all three groups, except that antioxidants were added to the TRIS-egg-yolk freezing extender for those semen samples that were already sorted in the presence of antioxidants. The semen quality in frozen-thawed samples was determined by morphology analysis immediately after thawing, motility estimation in a thermo-resistance test after 0, 6, 12 and 24 h incubation at 37°C and Fluorescein isothiocyanate conjugated PNA/propidium iodide (FITC-PNA/PI) staining after 0, 12 and 24 h of incubation at 37°C. There was a significantly higher (p < 0.05) percentage of motile spermatozoa in S-AO samples in comparison to unsorted frozen-thawed control at 0, 6 and 24 h after thawing and compared with normally sorted samples at all times after thawing. The percentage of damaged acrosomes was significantly lower (p < 0.05) in S-AO samples than in the unsorted controls (20.8 ± 6.9% vs 30.3 ± 12.0%). The percentage of morphologically abnormal spermatozoa in this group was significantly lower (p < 0.05) than in the unsorted controls and normally sorted samples (25.8 ± 5.2%, 36.0 ± 12.5% and 35.1 ± 7.4%, respectively). Analysis of frozen-thawed spermatozoa with FITC/PI revealed no significant difference in membrane integrity at 0 and 12 h after sorting, but after 24 h of incubation the S-AO samples had a significantly higher (p < 0.001) percentage of spermatozoa with intact membranes in comparison to unsorted controls and normally sorted semen (40.7 ± 6.3%, 7.8 ± 4.7% and 7.4 ± 4.6%, respectively). The percentage of acrosome-reacted spermatozoa was significantly lower (p < 0.05) in the S-AO samples than in the unsorted controls (14.1 ± 7.5%, 23.4 ± 5.4% and 28.8 ± 6.3% vs 25.9 ± 14.4%, 38.5 ± 16.7% and 79.8 ± 4.1%, for 0, 12 and 24 h after thawing, respectively) and in comparison to normally sorted semen 24 h after thawing (67.3 ± 10.0%). This study demonstrates the highly protective effects of antioxidants on the quality of flow cytometrically sorted frozen-thawed bull spermatozoa. [source]

REVIEW ARTICLE: Clinical Relevance of Oxidative Stress in Male Factor Infertility: An Update

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2008
Ashok Agarwal
Male factor has been considered a major contributory factor to infertility. Along with the conventional causes for male infertility such as varicocele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma, and tumors, a new, yet important cause has been identified: oxidative stress. Oxidative stress (OS) is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body, which can lead to sperm damage, deformity and eventually male infertility. This involves peroxidative damage to sperm membrane and DNA fragmentation at both nuclear and mitochondrial levels. OS has been implicated as the major etiological factor leading to sperm DNA damage. OS-induced DNA damage can lead to abnormalities in the offspring including childhood cancer and achondroplasia. In this article, we discuss the need of ROS in normal sperm physiology, the mechanism of production of ROS and its pathophysiology in relation to male reproductive system. The benefits of incorporating antioxidants in clinical and experimental settings have been enumerated. We also highlight the emerging concept of utilizing OS as a method of contraception and the potential problems associated with it. [source]

Erythrocyte Susceptibility to Oxidative Stress in Chronic Renal Failure Patients Under Different Substitutive Treatments

ARTIFICIAL ORGANS, Issue 1 2005
Leonardo Lucchi
Abstract:, An increased oxidative stress is now considered one of the major risk factors in chronic renal failure (CRF) patients that may be exacerbated by dialysis. It has been postulated that this increased oxidative stress might cause an augmented red blood cell (RBC) membrane lipid peroxidation with the consequent alteration in membrane deformability. The aim of this study was to evaluate RBC susceptibility to an in vitro induced oxidative stress and RBC antioxidant potential in different groups of CRF patients undergoing different substitutive treatment modalities. Fifteen end-stage CRF patients were evaluated in conservative treatment, 23 hemodialysis (HD) patients, 15 continuous ambulatory peritoneal dialysis (CAPD) patients, 15 kidney transplanted patients, and 16 controls. Their RBCs were incubated with the oxidative stress-inducing agent tert-butylhydroperoxide both in the presence and in the absence of the catalase inhibitor sodium azide, and the level of malondialdehyde (MDA) (a product of lipid peroxidation), was measured at 0, 5, 10, 15, and 30 min of incubation. In addition, the RBC content of reduced glutathione (GSH) was measured by HPLC. As opposed to the controls, RBCs from end-stage CRF patients exhibited an increased sensitivity to oxidative stress induced in vitro, both in the absence and presence of a catalase inhibitor, as demonstrated by a significantly higher level of MDA production at all the incubation times (P < 0.05). Different substitutive treatments had different impacts on this phenomenon; CAPD and kidney transplantation were able to normalize this alteration while HD was not. GSH appeared to be related to the increase in RBC susceptibility to oxidative stress; its content being significantly elevated in end-stage CRF and HD patients as compared with CAPD and transplanted patients and controls (P < 0.05). No significant changes were observed in the RBC glutathione content during the HD session. The increase of GSH in RBCs of end-stage CRF and HD patients seems to indicate the existence of an adaptive mechanism under increased oxidative stress occurring in vivo. Unlike HD, the beneficial effect of CAPD on the anemia of dialysis patients might partly be due to a condition of lower oxidative stress that might in addition counterbalance the cardiovascular negative effects of dislipidemia ,of, CAPD, patients. [source]

Effects of a Vitamin E-Modified Dialysis Membrane and Vitamin C Infusion on Oxidative Stress in Hemodialysis Patients

ARTIFICIAL ORGANS, Issue 6 2001
Jaromír Eiselt
Abstract: Hemodialysis deteriorates oxidative stress. Vitamin E is an antioxidant whose regeneration is provided for by vitamin C. The authors tested the effects of a vitamin E-modified membrane (E), nonmodified cellulose membrane (O), and vitamin C infusion (500 mg, C) into the arterial blood line during dialysis on parameters of oxidative stress. In a short-term study, 24 patients were subjected to a single dialysis session with E, O, E with C, and O with C protocols. In a long-term study (12 weeks), 20 patients were randomized into groups with C and without C on each dialysis, and both groups had dialysis using O, E, and again O membrane for 4 weeks each. In the short-term study, thiobarbituric acid reacting substances (TBARS) in plasma rose after dialysis (p < 0.02) with O, and no changes were observed in the other 3 protocols. In the long-term study, predialysis TBARS declined when using E both in the groups with C (p < 0.02) and without C (p < 0.05). A switch over to O resulted in TBARS returning to baseline levels. The E membrane prevented an increase in lipid peroxidation during single dialysis, and long-term use of the E membrane also resulted in a decrease in the predialysis lipid peroxidation level. The antioxidant capacity of the E membrane was not enhanced by vitamin C infusion. High doses of vitamin C administered during dialysis using a nonmodified cellulose membrane prevented an increase in lipid peroxidation, most probably due to the enhanced rate of endogenous vitamin E regeneration. [source]

Influence of Different Hemodialysis Membranes on Red Blood Cell Susceptibility to Oxidative Stress

ARTIFICIAL ORGANS, Issue 1 2000
Leonardo Lucchi
Abstract: Oxidative stress is crucial in red blood cell (RBC) damage induced by activated neutrophils in in vitro experiments. The aim of the study was to evaluate whether the bioincompatibility phenomena occurring during hemodialysis (HD) (where neutrophil activation with increased free radical production is well documented) may have detrimental effects on RBC. We evaluated RBC susceptibility to oxidative stress before and after HD in 15 patients using Cuprophan, cellulose triacetate, and polysulfone membrane. RBC were incubated with t-butyl hydroperoxide as an oxidizing agent both in the presence and in the absence of the catalase inhibitor sodium azide. The level of malonaldehyde (MDA), a product of lipid peroxidation, was measured at 0, 5, 10, 15, and 30 min of incubation. When Cuprophan membrane was used, the MDA production was significantly higher after HD, indicating an increased susceptibility to oxidative stress in comparison to pre-HD. The addition of sodium azide enhanced this phenomenon. Both cellulose triacetate and polysulfone membranes did not significantly influence RBC susceptibility to oxidative stress. Neither the level of RBC reduced glutathione nor the RBC glutathione redox ratio changed significantly during HD with any of the membranes used. The RBC susceptibility to oxidative stress was influenced in different ways according to the dialysis membrane used, being increased only when using the more bioincompatible membrane Cuprophan, where neutrophil activation with increased free radical production is well documented. The alterations found in this study might contribute to the reduced RBC longevity of HD patients where a bioincompatible membrane is used. [source]

Hepatoprotective Activity of Polyherbal Formulation (Normeta®) in Oxidative Stress Induced by Alcohol, Polyunsaturated Fatty Acids and Iron in Rats

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2009
Shilpa N. Patere
The present study was carried out to evaluate the effects of oral treatment with polyherbal formulation Normeta® (2 ml and 4 ml/kg) on hepatic damage induced by alcohol 10,30% (blood alcohol was maintained at levels between 150 and 350 mg/dl), thermally oxidized oil (polyunsaturated fatty acids) (15% of diet) and carbonyl iron (1.5,2% of diet) for 30 days in rats. In vitro studies with 1, 1-Diphenyl, 2-Picrylhydrazyl (DPPH), Nitric oxide and Ferric chloride (Fe+3 ions) showed that Normeta® possesses antioxidant and metal chelating activity. Alcohol, polyunsaturated fatty acids and iron feeding produced an increase in serum levels of iron, serum glutamate pyruvate transaminase and decrease in serum proteins. It was also associated with elevated lipid peroxidation (thiobarbituric acid reactive substances) and disruption of antioxidant defence mechanism in liver, decreased body weight and increased liver to body weight ratio. Oral administration of Normeta® along with alcohol, polyunsaturated fatty acids and iron decreased the serum iron, serum glutamate pyruvate transaminase levels and increased serum protein levels. The levels of liver thiobarbituric acid reactive substances were decreased and the activities of antioxidant enzymes superoxide dismutase and catalase were increased. Improvement in body weight and liver to body weight ratio was also observed. The effects of Normeta® on physico-metabolic parameters were comparable with silymarin. This indicates that Normeta® has favourable effect in bringing down the severity of hepatotoxicity. [source]

Oxidative Stress Alters Creatine Kinase System in Serum and Brain Regions of Polychlorinated Biphenyl (Aroclor 1254)-Exposed Rats: Protective Role of Melatonin

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009
Prabhu Venkataraman
Creatine kinase plays a key role in energy metabolism of nervous tissue and might be one of the targets for reactive oxygen species. Melatonin, an indoleamine, plays an important role in neurodegenerative diseases as an antioxidant and neuroprotector. The objective of the present study was to investigate the protective role of melatonin on polychlorinated biphenyl (Aroclor 1254)-induced oxidative stress and the changes in creatine kinase activity in brain regions of adult rats. Group I: rats were intraperitoneally (i.p.) administered with corn oil (vehicle) for 30 days. Group II: rats injected i.p. with Aroclor 1254 at 2 mg/kg body weight (bw)/day for 30 days. Groups III and IV: rats i.p. received melatonin (5 or 10 mg/kg bw/day) simultaneously with Aroclor 1254 for 30 days. After 30 days, rats were killed and the brain regions were dissected to cerebral cortex, cerebellum and hippocampus. Lipid peroxidation, hydroxyl radical and hydrogen peroxide (H2O2) levels were determined. The activity of creatine kinase was assayed in serum and brain regions, and its isoenzymes in serum were separated electrophoretically. Activity of creatine kinase was decreased while an increase in H2O2, hydroxyl radical and lipid peroxidation was observed in brain regions of polychlorinated biphenyl-treated rats. Also polychlorinated biphenyl exposure showed a significant increase in serum creatine kinase level and its isoforms such as BB-creatine kinase, MB-creatine kinase, and MM-creatine kinase. Administration of melatonin prevented these alterations induced by polychlorinated biphenyl by its free radical scavenging mechanism. Thus, polychlorinated biphenyl alters creatine kinase activity by inducing oxidative stress in brain regions, which can be protected by melatonin. [source]

Procyanidins Produce Significant Attenuation of Doxorubicin-Induced Cardiotoxicity via Suppression of Oxidative Stress

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2009
Wei Li
The major side effect of doxorubicin is oxidative injury-related cardiotoxicity, which has dramatically hindered its usage. Procyanidins from grape seeds are potent free radical scavengers that have been shown to protect against anthracycline-induced cardiotoxicity. In the present study, we tested whether procyanidins would prevent the doxorubicin-induced cardiotoxicity in rats. Rats were intraperitoneally treated with doxorubicin at a cumulative dose of 15 mg/kg with and without pre-administration of procyanidins. Our data showed that doxorubicin led to cardiac function deterioration, myocardial injury and increased oxidative stress in cardiac tissues. The cardiac function deterioration by doxorubicin included increased QT-interval and ST-interval in electrocardiograph (ECG) and decreased left ventricular developed pressure. Doxorubicin-induced myocardial injury was shown by the increased creatine kinase, alanine aminotransferase and aspartate aminotransferase in serum as well as in myocardial lesions. Pretreatment with procyanidin (150 mg/kg daily) effectively hindered the adverse effects of doxorubicin, such as myocardial injury and impaired heart function. Procyanidin pretreatment attenuated cytoplasmic vacuolization, increased left ventricular developed pressure and improved the ECG. The cardioprotective effect of procyanidin corresponded to the decrease of lipid peroxidation and the increase of cardiac antioxidant potency in doxorubicin-treated rats that were also given procyanidin. An in vitro cytotoxic study showed that procyanidins did not attenuate the antineoplastic activity of doxorubicin to A549 adenocarcinoma cells. All the above lines of evidence suggest that procyanidins protect cardiomyocytes from doxorubicin-induced cardiotoxicity via suppression of oxidative stress. [source]

Lycopene, a Carotenoid, Attenuates Cyclosporine-Induced Renal Dysfunction and Oxidative Stress in Rats

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2007
Ahmet Ate, ahin
Adult male Sprague-Dawley rats were randomly divided into four groups. The control group received physiological saline; animals in the lycopene group received only lycopene (10 mg/kg); animals in the cyclosporine A group received only cyclosporine A (15 mg/kg) and animals in cyclosporine plus lycopene group received cyclosporine and lycopene for 21 days. The effects of lycopene on cyclosporine A-induced nephrotoxicity were evaluated by plasma creatinine, urea, sodium and calcium concentrations; kidney tissue thiobarbituric acid reactive species, reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and catalase activities and histopatological examinations. Administration of cyclosporine A to rats induced a marked renal failure, characterized with a significant increase in plasma creatinine and urea concentrations. Cyclosporine A also induced oxidative stress as indicated by increased kidney tissue concentrations of thiobarbituric acid reactive species and GSH, and reduced activities of GSH-Px and catalase. Moreover, the kidneys of cyclosporine A-treated rats showed tubular necrosis, degeneration, dilatation, thickened basement membranes, luminal cast formation and inter-tubular fibrosis. Lycopene markedly reduced elevated plasma creatinine, urea levels and counteracted the deleterious effects of cyclosporine A on oxidative stress markers. In addition, lycopene ameliorated cyclosporine A-induced pathological changes including tubular necrosis, degeneration, thickened basement membranes and inter-tubular fibrosis when compared to the alone cyclosporine A group. These data indicate that the natural antioxidant lycopene might have protective effect against cyclosporine-induced nephrotoxicity and oxidative stress in rat. [source]

Attenuation of Oxidative Stress in Plasma and Tissues of Rats with Experimentally Induced Hyperthyroidism by Caffeic Acid Phenylethyl Ester

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2007
Ahmed M. Mohamadin
The present study was designed to investigate the protective effects of caffeic acid phenylethyl ester (CAPE) on oxidative damage in rats with experimentally induced hyperthyroidism. The study was conducted on 32 male Sprague-Dawley rats. The experimental animals were divided into four groups (control, CAPE alone, hyperthyroidism, and hyperthyroidism + CAPE). Hyperthyroidism was induced by intraperitoneal administration of 0.3 mg/kg/day l -thyroxine for 4 weeks. CAPE (10 µg/kg) was administered intraperitoneally for 4 weeks. At the end of the experimental period, blood samples and various organs (liver, heart and brain) of rats were taken for the determination of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), oxidized glutathione, vitamin C and superoxide dismutase (SOD) levels and concentrations of triiodothyronine (T3), thyroxine (T4) and thyroxine-stimulating hormone (TSH). Our results indicate that TBARS, oxidized glutathione, SOD levels and concentrations of T3 and T4 were higher in plasma and tissues of the hyperthyroid group compared to controls. Vitamin C, GSH and TSH levels were decreased significantly in the hyperthyroid group when compared to the control group. CAPE treatment decreased the elevated TBARS, SOD, T3 and T4 levels and increased the lowered GSH, vitamin C and TSH levels to control levels in rats with hyperthyroidism. In conclusion, our results indicate that CAPE is beneficial as a protective agent against oxidative stress induced by hyperthyroidism in rats. The protection is probably due to multiple mechanisms involving free radical scavenger properties, attenuating lipid peroxidation and increasing the antioxidant status. [source]

Heroin-Administered Mice Involved in Oxidative Stress and Exogenous Antioxidant-Alleviated Withdrawal Syndrome

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2006
Bo Xu
It is well known that an increase in DA oxidative metabolism leads to increased reactive oxygen species (ROS) formation, and thus, ROS have been frequently associated with neuronal cell death due to damage to carbohydrates, amino acids, phospholipids, and nucleic acids. This study investigated whether there are oxidative stress and effects of exogenous antioxidants in heroin-administered mice. The heroin-dependent mice model was made via intraperitoneal injection. Oxidative damage of DNA, protein, and lipid was measured by analysis of single cell electrophoresis, the 2,4-dinitrophenylhydrazine method, and thiobarbituric acid method respectively. The activities of antioxidative enzymes and total antioxidant capacity were assayed by spectrophotometry. After administration with heroin, the mice not only showed decrease of total antioxidant capacity in serum and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione (GSH) peroxidase in brain, but also exhibited the oxidative damages of DNA, protein and lipid. On the other hand, exogenous antioxidants could restrain the oxidative stress, even alleviate withdrawal syndrome in heroin-administered mice. Our results also imply a possibility that ROS may participate in the whole process of dependence and withdrawal of heroin. Therefore, strategies of blocking oxidative stress may be useful in the development of therapy for opiate abuse. [source]