Effects of sesame oil on oxidative stress after the onset of sepsis in rats

The aim of this study was to investigate effects of sesame oil on oxidative stress after the onset of sepsis in rats. Effects of sesame oil on lipid peroxidation, superoxide anion, superoxide dismutase, catalase, glutathione, and nitrite after the onset of endotoxin intoxication were determined. To further examine the protective effect of sesame oil on sepsis, a mortality study was also conduced in cecal ligation and puncture-induced sepsis in rats. Sesame oil was given orally 6 h after endotoxin administration and cecal ligation and puncture, and parameters were then measured in another 6 h. Data demonstrated that a single dose of sesame oil reduced lipid peroxidation 6 h after endotoxin intoxication. Superoxide anion counts were decreased, glutathione levels were increased, and activities of superoxide dismutase and catalase, as well as nitrite levels, were not altered in lipopolysaccharide plus sesame oil-treated groups compared with lipopolysaccharide-treated groups. Furthermore, sesame oil given 6 h after cecal ligation and puncture significantly increased survival rate. Thus, we suggested that sesame oil could be used as a potent antioxidant to reduce oxidative stress after the onset of sepsis in rats.     

Effects of insulin treatment on endoneurial and systemic oxidative stress in relation to nerve conduction in streptozotocin-diabetic rats

As increased oxidative stress is probably a pathogenetic factor in the development of diabetic complications, we studied nerve function and endogenous antioxidants in plasma, erythrocytes and sciatic nerve of untreated and insulin-treated streptozotocin-diabetic rats. After 18 weeks, the diabetes-induced sciatic nerve conduction velocity deficits were approximately 65% improved by insulin ( P <0.001). Plasma superoxide dismutase was significantly reduced in diabetes ( P <0.01); smaller decreases in plasma catalase and glutathione levels were observed. These changes were corrected by insulin treatment. In erythrocytes, decreased superoxide dismutase ( P <0.05) and increased total glutathione levels ( P <0.05) were found. All effects of diabetes, including a rise in plasma malonyldialdehyde ( P <0.05), were partially reversed by insulin treatment. In nervous tissue, diabetes caused increased catalase activity, uninfluenced by insulin ( P <0.05). Nerve superoxide dismutase and glutathione did not change. The data suggest that, in diabetes, changes in systemic rather than endoneurial oxidative stress lead to nerve dysfunction.     

Efficacy of tadalafil in chronic hypobaric hypoxia–induced pulmonary hypertension: possible mechanisms

The present study was carried out to investigate the effects of long‐acting phosphodiesterase five inhibitor, tadalafil, on pulmonary hypertension induced by chronic hypobaric hypoxia in rats. Adult Albino Wistar rats were exposed to 2 weeks of hypobaric hypoxia for 8 h daily and treated with tadalafil or tempol, a standard antioxidant agent. Right ventricular systolic pressure (RVSP) was taken as an index for pulmonary arterial pressure; malondialdehyde, reduced glutathione and superoxide dismutase were chosen as the markers of oxidative stress; serum tumour necrosis factor alpha (TNF‐α) levels and inflammatory changes in lungs were assessed for inflammation. Chronic hypobaric hypoxia was found to induce pulmonary hypertension, as it significantly (P < 0.001) increased RVSP. Chronic hypobaric hypoxia also leads to an increase in oxidative stress as was evidenced by an increase in malondialdehyde levels (P < 0.001) and a significant decrease in (P < 0.001) reduced glutathione levels and superoxide dismutase activity. Chronic hypobaric hypoxia–induced inflammation was revealed by lung histology and increase in serum TNF‐α levels. Tadalafil significantly prevented (P < 0.001) rise in hypobaric hypoxia–induced rise in RVSP. Tadalafil partially while tempol completely reversed hypobaric hypoxia–induced oxidative stress. Lung inflammation and serum TNF‐α levels were significantly attenuated by both tadalafil and tempol. However, effect of tadalafil on inflammation was more marked than that of tempol. These data indicate that tadalafil possess antioxidant as well as antinflammatory action in addition to its vasodilatory property. All these three actions combined may have positive impact of tadalafil in the treatment of hypobaric hypoxia–induced pulmonary hypertension.     

S-adenosyl-L-methionine attenuates hepatotoxicity induced by agonistic Jo2 Fas antibody following CYP2E1 induction in mice

S-Adenosyl-l-methionine (SAM) has been shown to be hepatoprotective against many toxic agents. Its possible effectiveness in protecting against CYP2E1-dependent toxicity is not known. We recently reported that treatment of mice with pyrazole to induce CYP2E1 increased hepatotoxicity produced by Fas agonistic Jo2 antibody. The current study was designed to investigate the effect of exogenous administration of SAM on the synergistic hepatotoxicity produced by Fas agonistic Jo2 antibody plus CYP2E1 following pyrazole pretreatment in C57BL/6 mice. Suboptimal administration of Jo2 Fas antibody combined with pyrazole pretreatment caused severe hepatotoxicity as determined by elevations in serum transaminase levels and histopathology. Exogenous administration of SAM (50 mg i.p./kg body weight every 12 h for 3 days) significantly decreased serum transaminases and ameliorated morphological changes of the liver. Addition of SAM elevated hepatic SAM and total reduced glutathione levels and inhibited CYP2E1 activity. SAM also lowered the elevated oxidative stress (lipid peroxidation, protein carbonyls, and superoxide production) and nitrosative stress (induction of inducible nitric-oxide synthase and 3-nitrotyrosine adducts) and increases in caspase-8 and -3 activation produced by the pyrazole plus Jo2 treatment. SAM did not prevent the increase in serum TNF-alpha levels or the decrease in catalase activity in this model. These results indicate that SAM can have an important hepatoprotective role as an effective reagent against Fas plus CYP2E1-induced hepatotoxicity by lowering oxidative and nitrosative stress.     

The nitroxide tempol has similar antioxidant effects as physiological levels of 17β‐oestradiol in reversing ovariectomy‐induced oxidative stress in mice liver and kidney

Objective: Oestrogen defciency increases oxidative stress postmenopause, while tempol is an intracellular radical scavenger that interferes with the formation or effects of many radicals. We aimed to investigate the effects of oestrogen and tempol on oxidative stress parameters in the kidney and liver of ovariectomized mice. Material and methods: Forty 8‐week‐old female Bald/c mice were divided into five groups: sham‐operated, ovariectomized mice without treatment, ovariectomized mice treated with tempol, ovariectomized mice treated with 17β‐oestradiol and ovariectomized mice treated with 17β‐oestradiol and tempol. Oxidative stress in liver and kidney tissues was investigated by measuring 2‐thiobarbituric acid reactive substances (TBA‐RS), reduced glutathione, myeloperoxidase, superoxide dismutase and catalase levels. Results: TBA‐RS levels were increased and reduced glutathione, myeloperoxidase, superoxide dismutase levels were decreased in the tissues of ovariectomized mice. This effect of ovariectomy on oxidative stress parameters was opposed significantly by the administration of tempol and 17β‐oestradiol either alone or in combination. Ovariectomy reduced the kidney catalase levels, but the effect was not statistically significant (p>0.05). On the other hand, catalase levels were elevated significantly in all treatment groups compared to those of the ovariectomized group (p<0.05). Conclusion: These study findings demonstrate that tempol significantly opposes the oxidative stress generated by ovariectomy. This effect, which is evident in remote tissues such as liver and kidney, is comparable to that of physiological levels of oestradiol.     

Plasma oxidants and antioxidants in acute ischaemic stroke

Plasma levels of the oxidants xanthine oxidase, nitric oxide and malondialdehyde and the antioxidants superoxide dismutase, glutathione peroxidase and glutathione reductase, together with total superoxide scavenger activity and non-enzymatic superoxide scavenger activity, were determined in 19 patients with acute ischaemic stroke and 20 controls. Compared with controls, superoxide dismutase, total superoxide scavenger activity, glutathione peroxidase and glutathione reductase activities were significantly lower, and nitric oxide and malondialdehyde levels significantly higher, in acute stroke patients. Xanthine oxidase showed a slight but non-significant increase in stroke patients compared with controls. There was no significant difference in non-enzymatic superoxide scavenger activity between the two groups. There was a positive correlation between glutathione reductase levels and Glasgow Coma Scale scores, and a negative correlation between malondialdehyde levels and non-enzymatic superoxide scavenger activity. These findings suggest that oxidative stress in patients with acute ischaemic stroke may be the result of an imbalance in oxidant/antioxidant homeostasis.     

Oxidative stress and male IGF-1, gonadotropin and related hormones in diabetic patients.

Elevation of glucose concentration in diabetes may induce generation of oxygen free radicals such as superoxide (O2*-) and hydroxyl (*OH). The aim of the present study was to investigate the effect of the oxidative stress on the activities of blood superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and aldose reductase, the levels of reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid reactive substances; TBARS) and plasma levels of insulin-like growth factor-1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone in type 2 (non-insulin-dependent diabetes) patients and in healthy controls. Blood SOD, CAT, GSH-Px and GSSG-R were lower in type 2 diabetic patients compared with the the control group. Blood aldose reductase activity was elevated in patients with type 2 diabetes compared with the control group. GSH was decreased while TBARS concentration was increased in red blood cells (RBC) and leukocytes from the patients with type 2 diabetes mellitus in comparison to the control group. The mean values of plasma LH, FSH and testosterone were decreased, whereas the mean plasma IGF-1 concentration was increased in type 2 diabetes compared with controls. These findings support the hypothesis that hyperglycemia enhances the activity of the polyol pathway and impairs the antioxidant status, particularly glutathione redox cycle, resulting in poorer defense against oxidative stress. In addition, decreased circulating testosterone and gonadotropin levels may reflect the oxidative stress exerted by diabetes.     

Housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats

The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC) housed in home cage and left in the laboratory; restrained rats (with three subgroups) subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC) having their restrainers kept in the laboratory; restrained pyramid rats (RP) being kept in the pyramid; and restrained square box rats (RS) in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA) and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH) levels, erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.     

Comparative effect of topical application of lindane and permethrin on oxidative stress parameters in adult scabies patients

OBJECTIVES: The insecticides lindane and permethrin are commonly used for treatment of scabies. Animal studies have shown the presence of insecticide induced oxidative stress. Hence, this study was undertaken to assess and compare the effects of topical application of lindane and permethrin on oxidative stress parameters in scabies patients. DESIGN AND METHODS: Patients were alternatively assigned to treatment by either 1% lindane lotion or 5% permethrin cream. Blood samples were collected before and 12-14 h after the application of the drugs and evaluated for oxidative stress parameters and compared with healthy controls. RESULTS: Serum malondialdehyde (MDA) levels, erythrocyte superoxide dismutase (SOD) and catalase (CAT) activity were significantly increased while blood glutathione (GSH) levels were significantly decreased in the lindane group as compared to controls and the permethrin group. The permethrin treated group showed a non significant alteration in the oxidative stress parameters. CONCLUSION: Topical application of lindane induced significant oxidative stress as compared to permethrin which appears to be a safer option for the treatment of scabies.     

Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-L-cysteine in rats.

OBJECTIVES: The objectives of this study were to examine the role of reactive oxygen species and oxidative stress in peripheral neuropathy and behavioural pain responses in experimentally induced chronic constriction injury (CCI) of sciatic nerve of rat. Effect of N-acetyl-L-cysteine (NAC) administered intraperitoneally, was also investigated on CCI-induced neuropathic pain in rats. METHODS: Neuropathy was induced by CCI of the right sciatic nerve in ketamine anaesthetized rats. Effect of intraperitoneally administered NAC in rats was also investigated using nociceptive behavioural tests. Malondialdehyde, an index of oxidative stress and antioxidant enzymes was also estimated in ligated sciatic nerve. RESULTS: Behavioural tests, mechanical, thermal and cold stimuli confirmed the development of neuropathic pain after the CCI. The malondialdehyde levels of ligated sciatic nerves were significantly increased compared to non-ligated sciatic nerves (sham operated). The antioxidant enzyme reduced, glutathione was inhibited, while superoxide dismutase increased. However, catalase remained unaffected in the injured sciatic nerves. Intraperitoneal administration of NAC resulted in significant reduction of hyperalgesia in CCI-induced neuropathic rats. CONCLUSIONS: This study identifies antioxidants superoxide dismutase and reduced glutathione, and oxidative stress as important determinants of neuropathological and behavioural consequences of CCI-induced neuropathy, and NAC may be a potential candidate for alleviation of neuropathic pain.     

新诊断2型糖尿病患者氧化应激状况及短期胰岛素泵强化治疗的影响

【目的】观察初诊2型糖尿病（T2DM）患者体内氧化应激改变及短期持续皮下胰岛素输注（CSII）治疗对患者氧化应激状况的影响。[方法]60例初诊T2DM患者接受为期2周的CSII治疗,于治疗前、后分别测定血清活性氧活力（ROS）、丙二醛（MDA）、谷胱甘肽（GSH）、超氧化物歧化酶（SOD）,同时测定T2DM患者空腹胰岛素水平,采用稳态模型计算胰岛β细胞功能（HOMA-β）。【结果】①T2DM患者ROS、MDA明显增高,GSH、SOD明显降低。②ROS、MDA与HOMA—β呈负相关,GSH、SOD与HOMA—β呈正相关。③CSII治疗2周后,ROS、MDA明显降低,GSH、SOD明显增高,同时HOMA-β亦明显增高。[结论]T2DM患者体内氧化应激明显增强。短期CSII除迅速降低血糖外,还具有降低T2DM患者氧化应激水平,保护胰岛口细胞功能。     

Effects of Therapeutic Pulsed Ultrasound and Dimethylsulfoxide (DMSO) Phonophoresis on Parameters of Oxidative Stress in Traumatized Muscle

Many studies have demonstrated an increase in reactive oxygen species (ROS) and oxidative damage markers after muscle damage. Phonophoresis aims to achieve therapeutically relevant concentrations of the transdermally introduced drug in the tissues subjected to the procedure by the use ultrasound waves. The aim of the study was to evaluate the effects on the therapeutic pulsed ultrasound (TPU) together with gel-dimethylsulfoxide (DMSO) in the parameters of muscular damage and oxidative stress. Male Wistar rats were divided randomly into six groups (n = 6): sham (uninjured muscle); muscle injury without treatment; muscle injury and treatment with gel-saline (0.9%); muscle injury and treatment with gel-DMSO (15 mg/kg); muscle injury and TPU plus gel-saline; and muscle injury and TPU plus gel-DMSO. Gastrocnemius injury was induced by a single impact blunt trauma. TPU (6 min duration, frequency of 1.0 MHz, intensity of 0.8 W/cm²) was used 2, 12, 24, 48, 72, 96 and 120 h after muscle trauma. The CK and acid phosphatase activity in serum was used as an indicator of skeletal muscle injury. Superoxide anion, TBARS, protein carbonyls, superoxide dismutase (SOD) and catalase (CAT) activity was used as indicators of stress oxidative. Results showed that TPU and gel-DMSO improved muscle healing. Moreover, superoxide anion production, TBARS level and protein carbonyls levels, superoxide dismutase (SOD) and catalase (CAT) activity were all decreased in the group TPU plus gel-DMSO. Our results show that DMSO is effective in the reduction of the muscular lesion and in the oxidative stress after mechanical trauma only when used with TPU. (E-mail: silveira_paulo2004@yahoo.com.br)     

Superoxide anion radical, lipid peroxides and antioxidant status in the blood of patients with breast cancer

BACKGROUND: Reactive oxygen species (ROS), including superoxide anion radical (O2(-)), plays an important role in carcinogenesis. The human body has developed different antioxidant systems to defend against free radical attacks. We investigated the changes of the antioxidant status in the blood of patients with breast cancer. METHODS: The O2(-) generation and the levels of malondialdehyde (MDA) were measured as an index of lipid peroxidation along with the examination of the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), the levels of reduced glutathione (GSH), oxidized glutathione (GSSG), and vitamins A, C, and E. RESULTS: The results showed that the levels of O2(-) and MDA, and the activities of antioxidant enzymes in the blood of the patients with breast cancer were significantly higher than the controls. However, the levels of vitamin C, GSH, GSSG and ratio of GSH/GSSG in the blood of the patients with breast cancer were significantly decreased compared to control subjects. CONCLUSIONS: Oxidative stress may be involved in breast cancer. The increased activities of erythrocyte antioxidant enzymes may be a compensatory upregulation in response to the increased oxidative stress.     

Uric acid and allantoin levels in Down syndrome: antioxidant and oxidative stress mechanisms?

BACKGROUND: Down syndrome (DS) is a chromosomal abnormality (trisomy 21) leading to mental retardation, to the characteristic change of individual's phenotype and to the pathological features of Alzheimer disease. Patients with DS have elevated ratio of superoxide dismutase to (catalase plus glutathione peroxidase) with respect to controls in all age categories suggesting that oxidative imbalance contributes to the clinical manifestation of accelerated aging. RESULTS: We report that persons with DS have elevated uric acid levels compared with controls, 348.56+/-22.78 versus 284.00+/-20.86 micromol/l (p=0.018). The levels of hypoxanthine and xanthine in DS children (6.35+/-0.31 and 1.02+/-0.23 micromol/l) were significantly lower than in controls (7.83+/-0.59 and 2.43+/-0.66 micromol/l). This result suggests increased conversion of hypoxanthine and xanthine to uric acid with subsequent free radical-dependent oxidation of uric acid to allantoin, mechanisms potentiated by the oxidative stress in DS. Allantoin is a nonenzymatic oxidative product of uric acid in human. In DS individuals, the levels of allantoin were significantly higher than those in healthy controls (18.58+/-2.27 and 14.07+/-1.07 micromol/l, respectively, p=0.03). CONCLUSIONS: Our data supported the presumption of increased oxidative stress in DS.     

复方片仔癀肝宝对酒精诱导的慢性肝损伤氧化应激的保护作用研究

目的:探讨复方片仔癀肝宝对酒精性肝病(Aleoholie Liver Disease,ALD)模型大鼠氧化应激的保护作用。方法:60只SPF级SD大鼠,随机分为正常对照组、模型组、阳性药对照组及肝宝低、中、高剂量组,每组10只。除正常对照组外其余各组用酒精联合高脂饲料喂养2周,造ALD模型,连续给药4周后取材。全自动生化仪检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)的含量变化;检测肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)的表达;HE染色,观察肝组织病理变化。结果 :模型组血清中ALT、AST、ALP、LDH的活性较正常对照组均有明显的上升,且肝组织中MDA水平明显上升,SOD、GSH-Px水平明显下降(P0.01)。与模型组相比,肝宝各组ALT、AST、ALP、LDH的活性及MDA水平明显降低,而SOD、GSH-Px水平明显上升(P0.05)。HE染色结果显示复方片仔癀肝宝不同剂量组对肝组织脂肪变性、肝内脂类聚集有明显的改善作用,并且存在剂量效应关系。结论:复方片仔癀肝宝能显著减轻酒精和高脂诱导的肝损伤,其机制可能与提高肝组织的抗氧化能力有关。     

Glucocorticoid Generates ROS to Induce Oxidative Injury in the Hippocampus, Leading to Impairment of Cognitive Function of Rats

The present study attempted to clarify whether over-secretion of glucocorticoids in the serum caused by increased hypothalamus-pituitary-adrenal activity induces oxidative stress in the rat brain, and how the stress causes the emergence of cognitive deficits. When rats were subcutaneously injected with corticosterone, lipid hydroperoxides and protein carbonyls increased markedly in the hippocampus in association with a decrease in activity of antioxidative enzymes, such as superoxide dismutase, catalase and glutathione peroxidase. These results suggest that high-level corticosterone in the serum induces reactive oxygen species (ROS), leading to oxidative damage in the hippocampus. After administration of corticosterone to rats, glucose and superoxide levels in the serum increased markedly. Furthermore, pyramidal cell apoptosis was observed to accompany the loss of glucocorticoid receptors at the cornus ammonis 1 region of the hippocampus. Rats injected with corticosterone showed marked deficits in memory function. The present results imply that ROS generated from the glycation reaction of increased glucose levels caused by gluconeogenesis activation through glucocorticoid with proteins in the serum attack the hippocampus to induce neurodegeneration, resulting in cognitive deficits in rats.     

Antioxidant status, lipid peroxidation and nitric oxide end products in patients of type 2 diabetes mellitus with nephropathy

OBJECTIVES: Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications including nephropathy. The aim of the present study was to evaluate oxidative stress status in Asian Indian patients of type 2 DM with nephropathy. DESIGN AND METHODS: Serum levels of malondialdehyde (MDA) and nitric oxide end products (nitrite and nitrate), activities of erythrocyte superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) content were estimated in controls, patients of type 2 DM without nephropathy (group 1) and with nephropathy (group 2). RESULTS: Serum MDA concentration was significantly high in both the groups of diabetic patients as compared to controls, (p < 0.05), with group 2 having a significantly higher value than group 1 (p < 0.05). Significantly elevated serum nitrite levels were found in diabetic patients as compared to controls (p < 0.001), however, no significant difference was found between group 1 and group 2. Moreover, serum nitrate as well as nitrite + nitrate levels were significantly higher in group 2 as compared to controls (p < 0.05). Activity of erythrocyte SOD and CAT was significantly reduced in both groups as compared to controls (p < 0.001) with catalase activity in group 2 being significantly lower than group 1 (p < 0.05). Erythrocyte GSH content was significantly lower in group 2 as compared to controls (p < 0.05) and group 1 (p < 0.05). CONCLUSIONS: Results of the present study indicate that oxidative stress is increased and antioxidant defenses are compromised in type 2 DM. These derangements are of a higher magnitude in patients of type 2 DM with nephropathy.     

Fat overload aggravates oxidative stress in patients with the metabolic syndrome

Background   Patients with the metabolic syndrome have greater levels of oxidative stress. However, as the response of markers of this stress to a fat overload is unknown, we evaluated certain markers of oxidative stress in these patients.
Material and methods   The study population comprised 93 subjects (70 men and 23 women): 13 healthy people (controls) with a mean age of 48·81 ± 9·01 years and 80 patients with the metabolic syndrome (mean age, 43·25 ± 11·55 years), according to the Adult Treatment Panel III criteria. All the participants were given a 60 g fat overload (Supracal). Three hours later the following biomarkers of oxidative stress were measured: lipid peroxidation products, protein carbonyl groups, reduced glutathione, glutathione peroxidase (GSH-Px), catalase, superoxide dismutase, glutathione reductase (GSH-Road) and glutathione S-transferase. The levels of oxidized glutathione (GSSG) were calculated.
Results   Compared with the controls, the patients showed greater baseline oxidative stress, higher levels of lipid peroxidation products and oxidized glutathione, and lower levels of reduced glutathione, glutathione peroxidase activity, glutathione reductase and glutathione transferase. This stress was more intense after the subjects received a fat overload, more so in the patients who experienced a greater reduction in GSHpx and GSHrd antioxidant activity and a greater increase in the levels of carbonylated proteins and lipoperoxides than the controls.
Conclusions   Patients with the metabolic syndrome have greater oxidative stress than healthy people. The variation in markers of this stress after a fat overload was even more pronounced in the patients.     

Metabolomics changes in a rat model of obstructive jaundice: mapping to metabolism of amino acids,carbohydrates and lipids as well as oxidative stress

The study examined the global metabolic and some biochemical changes in rats with cholestasis induced by bile duct ligation (BDL). Serum samples were collected in male Wistar rats with BDL (n = 8) and sham surgery (n = 8) at day 3 after surgery for metabolomics analysis using a combination of reversed phase chromatography and hydrophilic interaction chromatography (HILIC) and quadrupole-time-of-flight mass spectrometry (Q-TOF MS). The serum levels of malondialdehyde (MDA), total antioxidative capacity (T-AOC), glutathione (GSH) and glutathione disulfide (GSSG), the activities of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) were measured to estimate the oxidative stress state. Key changes after BDL included increased levels of l-phenylalanine, l-glutamate, l-tyrosine, kynurenine, l-lactic acid, LysoPC^c (14:0), glycine and succinic acid and decreased levels of l-valine, PC^b (19:0/0:0), taurine, palmitic acid, l-isoleucine and citric acid metabolism products. And treatment with BDL significantly decreased the levels of GSH, T-AOC as well as SOD, GSH-Px activities, and upregulated MDA levels. The changes could be mapped to metabolism of amino acids and lipids, Krebs cycle and glycolysis, as well as increased oxidative stress and decreased antioxidant capability. Our study indicated that BDL induces major changes in the metabolism of all 3 major energy substances, as well as oxidative stress.     

Influence of hyperhomocysteinemia on the cellular redox state--impact on homocysteine-induced endothelial dysfunction.

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. An increasing body of evidence has implicated oxidative stress as being contributory to homocysteine's deleterious effects on the vasculature. Elevated levels of homocysteine may lead to increased generation of superoxide by a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent, by an increase in the chemical oxidation of homocysteine and other aminothiols in the circulation. The resultant increase in superoxide levels is further amplified by homocysteine-dependent alterations in the function of cellular antioxidant enzymes such as cellular glutathione peroxidase or extracellular superoxide dismutase. One direct clinical consequence of elevated vascular superoxide levels is the inactivation of the vasorelaxant messenger nitric oxide, leading to endothelial dysfunction. Scavenging of superoxide anion by either superoxide dismutase or 4,5-dihydroxybenzene 1,3-disulfonate (Tiron) reverses endothelial dysfunction in hyperhomocysteinemic animal models and in isolated aortic rings incubated with homocysteine. Similarly, homocysteine-induced endothelial dysfunction is also reversed by increasing the concentration of the endogenous antioxidant glutathione or overexpressing cellular glutathione peroxidase in animal models of mild hyperhomocysteinemia. Taken together, these findings strongly suggest that the adverse vascular effects of homocysteine are at least partly mediated by oxidative inactivation of nitric oxide.