Plasma Thiobarbituric Acid Reactive Substances Research Articles

Antihyperglycaemic and antioxidant effect of hyponidd, an ayurvedic herbomineral formulation in streptozotocin-induced diabetic rats

Hyponidd is a herbomineral formulation composed of the extracts of ten medicinal plants ( Momordica charantia, Melia azadirachta, Pterocarpus marsupium, Tinospora cordifolia , Gymnema sylvestre, Enicostemma littorale, Emblica officinalis, Eugenia jambolana, Cassia auriculata and Curcuma longa). We have investigated hyponidd for its possible antihyperglycaemic and antioxidant effect in diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg kg(-1) body weight). Oral administration of hyponidd (100 mg kg(-1) and 200 mg kg(-1)) for 45 days resulted in significant lowered levels of blood glucose and significant increased levels of hepatic glycogen and total haemoglobin. An oral glucose tolerance test was also performed in experimental diabetic rats in which there was a significant improvement in blood glucose tolerance in the rats treated with hyponidd. Hyponidd administration also decreased levels of glycosylated haemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and alpha-tocopherol in diabetic rats. Plasma reduced glutathione and vitamin C were significantly elevated by oral administration of hyponidd. The effect of hyponidd at a dose of 200 mg kg(-1) was more effective than glibenclamide (600 microg kg(-1)) in restoring the values to near normal. The results showed that hyponidd exhibits antihyperglycaemic and antioxidant activity in STZ-induced diabetic rats.

Preventive effect of S-allyl cysteine sulfoxide (alliin) on cardiac marker enzymes and lipids in isoproterenol-induced myocardial injury

The present study was designed to evaluate the preventive effect of S-allyl cysteine sulfoxide (SACS) in isoproterenol (ISO)-induced myocardial ischaemia in male Wistar rats. Rats were pretreated with SACS (40 and 80 mg kg(-1) body-weight) for 5 weeks. After the treatment period, ISO (150 mg kg(-1) body-weight) was administered subcutaneously to rats at intervals of 24 h for 2 days. The activities of creatine kinase, creatine kinase-MB, lactate dehydrogenase, aspartate transaminase and alanine transferase were significantly increased in serum and significantly decreased in the hearts of ISO-treated rats. Pretreatment with SACS decreased the activities of these enzymes significantly in serum and significantly increased the activities in heart in ISO-treated rats. The levels of cholesterol, triglycerides and free fatty acids increased in serum and heart, while the levels of phospholipids increased in serum and decreased in heart in ISO-treated rats. SACS pretreatment showed a significant effect on the lipids studied. The activity of 3-hydroxy 3-methyl glutaryl coenzyme A (HMG CoA) reductase was significantly increased and the activity of lecithin cholesterol acyl transferase (LCAT) was significantly reduced in ISO-induced rats. Oral pretreatment with SACS significantly decreased the activity of HMG CoA reductase and significantly increased the activity of LCAT in ISO-induced rats. The levels of plasma thiobarbituric acid reactive substances and hydroperoxides were increased in ISO-treated rats. Pretreatment with SACS significantly decreased the levels of lipidperoxides in ISO-treated rats. The effect at a dose of 80 mg kg(-1) body-weight was more effective than at a dose of 40 mg kg(-1) body-weight and brought back all the biochemical parameters to near normal levels. Thus our study shows that SACS has a lipid-lowering effect in ISO-induced rats. Our study may have clinical relevance.

Alpha-lipoic Acid Improves Endothelial Dysfunction in Patients with Subclinical Hypothyroidism

Many studies showed that impairment of flow-mediated endothelium-dependent arterial dilation (FMD) exists in patients with subclinical hypothyroidism (sHT). The crucial mechanism of this endothelial dysfunction remain unclear. We hypothesized that oxidative stress may be partially responsible for the impairment in FMD in patients with sHT. Thus, the present study was designed to assess whether the antioxidant alpha-lipoic acid can improve endothelial dysfunction in patients with sHT. Forty women with newly diagnosed sHT and 18 healthy women with euthyroid status were enrolled. Patients were randomized into 2 groups to receive no treatment (n = 20), alpha-lipoic acid (n = 20) for 3 weeks. We measured the FMD at baseline and after 3 weeks. FMD in alpha-lipoic acid and no-treatment group were 3.92% and 4.02%, respectively, which were significantly lower than that in controls (5.64%) (p<0.001). After 3 weeks treatment, compared with before treatment in sHT patients, plasma thiobarbituric acid reactive substances (TBARS) levels decreased significantly in alpha-lipoic acid group (p<0.001), and remain unchanged in no-treatment group (p>0.05). FMD improved markedly (4.82%) in alpha-lipoic acid group (p<0.01), and remain unchanged in no-treatment group (p>0.05). The absolute changes in FMD showed significant negative correlation with the changes in TBARS (r = -0.773, p<0.001). Our data showed that sHT patients exists impaired endothelial function, and antioxidant alpha-lipoic acid can improve endothelial function, through decrease of oxygen- derived free radicals.

Vitamin E prevents steroid-induced osteonecrosis in rabbits

Background and purpose Prevention of osteonecrosis after corticosteroid administration would be important. We examined the potential of vitamin E (α-tocopherol) to reduce the incidence of corticosteroid-induced osteonecrosis in an animal model.Methods Japanese white rabbits were divided into 2 groups; the control group was fed a normal diet and the experimental group was fed α-tocopherol-supplemented diet in which α-tocopherol (600 mg/kg diet) was added to the normal diet. To induce osteonecrosis, high-dose methylprednisolone acetate (MPSL) (20 mg/kg body weight) was injected once into the right gluteus medius muscle of all rabbits. 4 weeks after the injection of MPSL, the presence or absence of osteonecrosis of bilateral femurs was examined histopathologically. The tocopherol/cholesterol ratios were calculated. The plasma levels of thiobarbituric acid-reactive substances (TBARS) were measured.Results Alpha-tocopherol-supplemented diet reduced the incidence of osteonecrosis, which developed in 14 of 20 rabbits in the control group and 5 of 21 rabbits in the experimental group (p = 0.004). The tocopherol/cholesterol ratio was higher in the experimental group than in the control group after the α-tocopherol administration. The plasma TBARS level was lower in the experimental group than in the control group at 4 weeks after the MPSL administration.Interpretation Our findings may offer a new approach for the prevention of corticosteroid-induced osteonecrosis.

Asymmetric dimethylarginine in angiotensin II-induced hypertension

Recent studies have shown that asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor, is increased in hypertension and chronic kidney disease. However, little is known about the effects of hypertension per se on ADMA metabolism. The purpose of this study was to test the hypothesis that ANG II-induced hypertension, in the absence of renal injury, is associated with increased oxidative stress and plasma and renal cortex ADMA levels in rats. Male Sprague-Dawley rats were treated with ANG II at 200 ng.kg(-1).min(-1) sc (by minipump) for 1 or 3 wk or at 400 ng.kg(-1).min(-1) for 6 wk. Mean arterial pressure was increased after 3 and 6 wk of ANG II; however, renal injury (proteinuria, glomerular sclerosis, and interstitial fibrosis) was only evident after 6 wk of treatment. Plasma thiobarbituric acid reactive substances concentration and renal cortex p22(phox) protein abundance were increased early (1 and 3 wk), but urinary excretion of isoprostane and H(2)O(2) was only increased after 6 wk of ANG II. An increased in plasma ADMA after 6 wk of ANG II was associated with increased lung protein arginine methyltransferase-1 abundance and decreased renal cortex dimethylarginine dimethylaminohydrolase activity. No changes in renal cortex ADMA were observed. ANG II hypertension in the absence of renal injury is not associated with increased ADMA; however, when the severity and duration of the treatment were increased, plasma ADMA increased. These data suggest that elevated blood pressure alone, for up to 3 wk, in the absence of renal injury does not play an important role in the regulation of ADMA. However, the presence of renal injury and sustained hypertension for 6 wk increases ADMA levels and contributes to nitric oxide deficiency and cardiovascular disease.

Anthropometric parameters, lipid peroxidation and antioxidants in autorickshaw drivers

Anthropometric and several biochemical parameters were estimated in smoking and alcoholic-smoking auto-drivers and compared with normal auto-rickshaw drivers and normal subjects. Auto-drivers had a lower height, weight, and body mass index (BMI) compared with age-matched normal subjects. Plasma thiobarbituric acid reactive substances (TBARS), total cholesterol, TC/HDL-C ratio, and lactic acid increased significantly and ascorbic acid, alpha-tocopherol, reduced glutathione (GSH), hemoglobin, and HDL-cholesterol decreased significantly in auto-drivers when compared with normal subjects. Total cholesterol and TC/HDL-C ratio increased significantly in smoking auto-drivers; TBARS increased and ascorbic acid, alpha-tocopherol, GSH, and hemoglobin decreased significantly in alcoholic-smoking auto-drivers. Exposure of automobile pollutants associated with habits (cigarette smoking, alcohol) causes profound alterations in the levels of lipid peroxidation, antioxidants, hemoglobin, total cholesterol, HDL-cholesterol, TC/HDL-C ratio and lactic acid.

Antioxidant therapy reverses impaired graft healing in hypercholesterolemic rabbits

Limited endothelial cell (EC) coverage and anastomotic intimal hyperplasia contribute to thrombosis and failure of prosthetic grafts. Lipid accumulation and lipid oxidation are associated with decreased EC migration and intimal hyperplasia. The goal of this study was to assess the ability of antioxidants to improve graft healing in hypercholesterolemic animals. Rabbits were placed in one of four groups: chow plus N-acetylcysteine (NAC), chow plus probucol, chow with 1% cholesterol plus NAC, or chow with 1% cholesterol plus probucol. After 2 weeks, expanded polytetrafluoroethylene grafts (12 cm long x 4-mm internal diameter) were implanted in the abdominal aorta. Grafts were removed after 6 weeks and analyzed for cholesterol content, EC coverage, anastomotic intimal thickness, and the cellular composition of the neointima. Plasma samples were obtained to assess systemic oxidative stress. The data were compared with previously reported data from animals fed diets of chow and chow with 1% cholesterol. Prosthetic grafts from rabbits fed chow with 1% cholesterol had significantly greater anastomotic intimal thickening and lower EC coverage than grafts from rabbits fed a regular chow diet. In hypercholesterolemic rabbits, antioxidant therapy decreased global oxidative stress as evidenced by a 40% decrease in plasma thiobarbituric acid reactive substances. In rabbits fed the chow with 1% cholesterol diet, NAC decreased intimal hyperplasia at the proximal anastomosis by 29% and significantly increased graft EC coverage from 46% to 71% (P = .03). Following a similar pattern, probucol decreased intimal hyperplasia by 43% and increased graft EC coverage to 53% in hypercholesterolemic rabbits. Global oxidative stress and anastomotic intimal hyperplasia are increased, and endothelialization of prosthetic grafts is significantly reduced in rabbits fed a high-cholesterol diet. Antioxidant treatment improves EC coverage and decreases intimal hyperplasia. Reducing oxidative stress may promote healing of prosthetic grafts.

Obesity is the major contributor to vascular dysfunction and inflammation in high-fat diet hypertensive rats

Obesity and hypertension are the two major risk factors that contribute to the progression of end-stage renal disease. To examine whether hypertension further exacerbates oxidative stress and vascular dysfunction and inflammation in obese rats, four groups of male Sprague-Dawley rats were fed either a normal (7% fat) or high-fat (36% fat) diet for 6 weeks and osmotic pumps were implanted to deliver ANG (angiotensin II) or vehicle for an additional 4 weeks.Treatment with the high-fat diet did not alter ANG-induced hypertension compared with the normal diet (174 +/- 6 compared with 170 +/- 5 mmHg respectively). Treatment with the high-fat diet increased body weight gain and plasma leptin levels and induced insulin resistance in normotensive and ANG-induced hypertensive rats. Plasma TBARS (thiobarbituric acid-reacting substances), a measure of oxidative stress, were elevated in high-fat diet-fed rats compared with controls (11.2 +/-1 compared with 8.4 +/- nmol/ml respectively) and was increased further in ANG-induced hypertensive rats fed a high-fat diet (18.8 +/-2.2 nmol/ml). Urinary nitrite excretion was also decreased in rats fed a high-fat diet without or with ANG infusion compared with controls. Afferent arteriolar relaxation to acetylcholine was impaired in rats fed the high-fat diet without or with ANG infusion. Renal cortical TNF-alpha(tumour necrosis factor-alpha), COX-2(cyclo-oxygenase-2) and phospho-IKK (inhibitor of nuclear factor k B kinase) expression increased in high-fat diet-fed rats compared with normal diet-fed rats. The increases in phospho-IKK and COX-2 expression were elevated further in ANG-induced hypertensive rats fed the high-fat diet.These results suggest that ANG-induced hypertension exacerbates oxidative stress and renal inflammation without further impairment in vascular dysfunction in high-fat diet-induced obesity.

Lycopene in the Prevention of Gastrointestinal Toxicity of Radiotherapy

We conducted a study to investigate if lycopene could reduce gastrointestinal toxicity of abdominal and pelvic radiation in Wistar albino rats. Animals received either a control diet (Group 1), lycopene-supplemented diet (Group 2), control diet and radiation (Group 3), and lycopene-supplemented diet plus radiation (Group 4). In Groups 2 and 4, the rats received 5 mg/kg/day lycopene for 10 days. In Groups 3 and 4, the rats received single fraction 8 Gy abdominal and pelvic radiation (RT) on Day 10. Study endpoints included weight loss, diarrhea, duration of diarrhea, survival, and an oxidative stress marker, plasma level of thiobarbituric acid reactive substance (TBARS). The rats receiving RT only had significantly higher weight loss rate compared to the lycopene plus RT group (P = 0.001). Plasma TBARS levels after RT were also significantly higher in the RT only group compared to lycopene plus RT group (P = 0.001). In conclusion, lycopene supplementation significantly reduced the weight loss and prevented oxidative stress in rats treated with abdominopelvic radiation.

Oxidative stress in liver and red blood cells in acute lindane toxicity in rats

The aim of our study was to determine the role and dynamics of oxidative and nitrosative stress, as well as superoxide dismutase (SOD) and catalase activity in the hepatocytes and erythrocytes in early phase of acute lindane intoxication. Male Wistar rats were divided into groups: control, dimethylsulfoxide and lindane-treated groups (L, 8 mg/kg, intraperitoneally). Animals were sacrificed 0.5 and 4 hours after treatment (L(0.5) and L(4) groups, respectively). Oxidative and nitrosative stress parameters and antioxidant enzymes were determined spectrophotometrically. Liver and plasma thiobarbituric acid reactive substances (TBARS) concentration were significantly increased 0.5 after lindane administration (p < .01), with subsequent additional rise within 4 hours (p < .01), while plasma nitrite + nitrate level was significantly higher only 4 hours after lindane treatment. Total liver SOD activity was significantly increased in L(4) group in comparison with control group (p < .01). In conclusion, oxidative and nitrosative stress play an important role in early phase of acute lindane hepatotoxicity. Antioxidant capacity of hepatocytes is partly increased, due to an adaptive increase in SOD activity.

Oxidant–antioxidant Status and Lipid Profile in the Hypertensive Patients.

Background: Hypertension is associated with an elevation of ROS and frequently also with an impairment of endogenous antioxidant mechanisms. Increased level of serum cholesterol, TG, VLDL has been observed in patients with hypertension. It has been shown that oxidized lipoprotein inactivates NO and aggravates hypertension. This study intends to know the association of oxidative stress and lipid profile with hypertensive patients of the Western Nepal.Methods: Our study group comprised of 32 confirmed cases of HTN. Inclusion criteria included the patients with blood pressure ≥140/90mm of Hg. Patients with secondary hypertension, past history of stroke, coronary artery disease (CAD), myocardial infarction, and peripheral vascular disease and diabetes mellitus were excluded. Serum lipid profile, plasma thiobarbituric acid reactive substances (PTBARS), plasma total antioxidant activity (TAA) and urinary thiobarbituric acid reactive substances (UTBARS) were estimated in these patients by standard procedures and the values were compared with 30 age, sex and socioeconomically matched normal healthy control subjects.Results: TBARS levels and Lipid profile were significantly raised in HTN patients, but TAA and urinary TBARS levels were comparable to normal subjects. BMI and W/H ratio in patients were comparable to control. Smoking and alcohol did not influence lipid profile, TBARS and TAA.Conclusion: Lipid profile and TBARS were significantly raised in HTN patients compare to controls. Thus, monitoring lipid level and maintaining oxidative balance in hypertensive patients would be helpful in preventing the diseases associated with hypertension. Key words: Hypertension; Lipid profile; Oxidative stress; Antioxidant; Nepal.doi: doi: 10.3126/jnhrc.v6i2.2185Journal of Nepal Health Research Council Vol. 6, No. 2, 2008 October Page : 63-68

Chronic treatment with pravastatin prevents early cardiovascular changes in spontaneously hypertensive rats

This study investigates the effect of pravastatin on blood pressure, cardiovascular remodelling and impaired endothelial function induced as early signs of cardiovascular disease in young spontaneously hypertensive rats (SHR). Eight-week-old SHR were treated for 4 weeks with pravastatin (20 mg kg(-1) day(-1)). Systolic blood pressure was measured periodically during the study using the tail-cuff method. At the end of the study, the left ventricular weight /body weight ratio was used as an index of left ventricular hypertrophy (LVH). Vascular function, superoxide (O(2)(-*)) production and structure were studied in aortic rings. Lipid peroxidation was measured in plasma (thiobarbituric acid reactive substances assay). Systolic blood pressure was lower in treated SHR than in control SHR, at the end of the study (171 +/- 1 vs. 159 +/- 2 mmHg, P < 0.05), and LVH was significantly reduced by pravastatin (2.7 +/- 0.02 vs. 2.5 +/- 0.01 mg g(-1), P < 0.05). Vascular responses to sodium nitroprusside and phenylephrine were similar in both groups; nevertheless, the relaxation response to acetylcholine was higher in the treated rats (45.6 +/- 2.6 vs. 58.1 +/- 3.2 %, P < 0.05). Vascular O(2)(-*) and plasma thiobarbituric acid reactive substances were reduced by pravastatin treatment, and urinary nitrites was elevated. Finally aortic wall became thinner after pravastatin treatment. Chronic treatment with pravastatin attenuated the increase of systolic blood pressure in SHR, prevented early LVH and improved vascular structure and function. These effects were accompanied by decreased measures of oxidative stress and improvements in NO production.

EFFECT OF n‐3 POLYUNSATURATED FATTY ACIDS ON OXIDATIVE STRESS IN RATS SUPPLEMENTED WITH DIFFERENT DOSES OF FISH OIL

ABSTRACT The diet and plasma lipid patterns associated with lipid oxidation susceptibility in rats fed different doses of polyunsaturated fatty acids (n‐3 PUFA) from fish oil were evaluated. Wistar rats were assigned into three groups and received diets containing 8% soybean oil (SOY), 4% soybean oil + 4% fish oil (SOY‐FISH) and 8% fish oil (FISH) for 21 days. Linoleic, oleic and α‐linolenic acids in SOY diets were substituted by myristic, palmitic, palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in SOY‐FISH and FISH diets reducing the n‐6/n‐3 ratio and increasing the peroxidability index (PI). Increased dietary EPA and DHA were observed in SOY‐FISH and FISH plasma at the expense of linoleic and arachidonic acid levels. Saturated fatty acids, which were significantly different between the three diets (P &lt; 0.01), were found at the same concentration in the plasma (P = 0.23). No changes were observed in oxidative stress as measured by the concentration of thiobarbituric acid reactive substances (TBARS) expressed in brain homogenates. However, TBARS concentration in the plasma of the SOY‐FISH group was higher than the other two groups (P = 0.02). The major differences between these three groups were the n‐3 PUFA content (0.4, 1.8 and 3.2 g/100 g diet) and the saturates/polyunsaturates ratio (0.3, 0.5 and 0.8) for SOY, SOY‐FISH, and FISH groups, respectively. Thus, n‐3 PUFA intake from fish oil only when followed by a decrease in saturated/polyunsaturated fatty acids ratio increased oxidative susceptibility in rats measured by plasma TBARS concentration.PRACTICAL APPLICATIONSBecause fish oil intake is associated with risk reduction for cardiovascular disease, individuals are taking supplements containing a high dose of fish oil. However, there is no scientific consensus if the intake of a high dose of fish oil could increase the oxidative stress. Thus, more studies are necessary to assure the safety of this kind of supplementation.

ANTIOXIDANT STATUS IN VIVO: THE CASE FOR REGULAR CONSUMPTION OF ANTIOXIDANT RICH FRUITS AND VEGETABLES

ANTIOXIDANT STATUS IN VIVO: THE CASE FOR REGULAR CONSUMPTION OF ANTIOXIDANT RICH FRUITS AND VEGETABLES

Effects of deep-frying oil on blood pressure and oxidative stress in spontaneously hypertensive and normotensive rats

Objective Ingestion of deep-frying oil has been reported to cause physiologic and histologic changes in experimental animals' tissue, increase the oxidative stress, and possibly lead to death. The purpose of this study was to investigate the effect of deep-frying oil on oxidative stress and blood pressure in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. Methods Deep-frying oil was prepared by frying fresh soybean oil at 180 ± 5°C for 8 h each day, for 4 consecutive days. Male SHR and WKY rats were fed diets containing 15% fresh soybean oil or deep-frying oil (DO) for 10 wk. Results Rats ingesting the DO diet had lower feed efficiency and higher relative liver and kidney weights but deep frying had no significant influence on blood pressure in WKY or SHR rats. The DO diet had no effect on plasma renin activity, aldosterone content, or tissue angiotension-I–converting enzyme activity. WKY rats fed the DO diet showed significantly increased urinary thromboxane B 2 and 8-iso-prostaglandin F 2α excretion, but not urinary 6-keto-prostaglandin F 1α excretion. Diets containing deep-frying oil resulted in increased plasma thiobarbituric acid-reactive substances and nitric oxide contents and decreased plasma total antioxidant capacity in SHR and WKY rats. Conclusion The ingestion of deep-frying oil seemed not to influence blood pressure or its related parameters, but altered eicosanoid metabolism and elevated oxidative stress in SHR and WKY rats.

Abstract: P1199 ENDOTHELIN-1 INHIBITS INSULIN-STIMULATED GLUCOSE UPTAKE IN SKELETAL MUSCLE IN VIVO AND IN VITRO

The potent vasoconstrictor endothelin-1 has been implicated in the pathogenesis of plasma oxidative stress seen in sepsis. The selective endothelin receptor blockers BQ123 andBQ788 were used to investigate the importance of selective endothelin receptor blockage in modulating oxidative stress during endotoxemia.The study was performed on male Wistar rats (n = 6 per group) divided into groups: (1) saline, (2) lipopolysaccharide (LPS) (15 mg\kg)-saline, (3) BQ123 (0.5 mg\kg)-LPS, (4) BQ123 (1 mg\kg)-LPS, (5) BQ788 (3 mg\kg)-LPS. The endothelin receptor type A (ETA-R) or type B (ETB-R) antagonist was injected intravenously 30 min before LPS administration. Blood pressure was monitored and blood was taken before, 90 min and 300 min after saline or LPS administration.Injection of LPS alone resulted in a decrease in mean arterial pressure (MAP) (p < 0.05), a decrease in ferric reducing ability of plasma (FRAP) value (p < 0.01) and a marked increase in plasma tumor necrosis factor α (TNF-α) and thiobarbituric acid reactive substances (TBARS) (p < 0.001, p < 0.001, respectively). Administration of BQ123 before LPS administration deteriorated MAP in a dose dependent way. Moreover, BQ123 (1 mg\kg) decreased plasma level of TBARS and TNF-α (p < 0.01 and p < 0.05, respectively) and increased FRAP value (p < 0.001). On the contrary, BQ788 prevented LPS-induced decrease in MAP (p < 0.001) and led to a significant reduction in plasma TBARS concentration (p < 0.01).Our study showed that blockage of ETB-R during endotoxemia improved blood hemodynamics and decreased plasma lipid peroxidation. Blockage of ETA-R improved plasma antioxidant status and decreased lipid peroxidation and TNF-a production, but it deteriorated hemodynamic conditions.

Effect of chronic smoking on lipid peroxidation and antioxidant status in gastric carcinoma patients

The effect of chronic cigarette smoking on lipid peroxidation and antioxidant status in 100 newly diagnosed patients with gastric cancer was studied. Equal number of age- and sex-matched healthy control subjects was taken as control. The level of plasma and erythrocyte thiobarbituric acid reactive substances (TBARS) was markedly increased in both the gastric cancer patients when compared to control subjects. The activities of enzymatic and non-enzymatic antioxidants were significantly decreased in both (smokers and non-smokers) gastric cancer groups when compared to control subjects. Comparatively, the increased TBARS level and decreased antioxidants level was observed in smokers than non-smoking gastric cancer patients. The present study highlights the occurrence of lipid peroxidation and possible breakdown of antioxidant status in cigarette smoking, which may subsequently increase the possibility of initiation and progression of gastric cancer.

Oxidative Stress Implication After Prolonged Storage Donor Heart with Blood Versus Crystalloid Cardioplegia and Reperfusion Versus Static Storage

Several factors are known to limit cardiac transplantation, such as number of donors, quality of cardiac graft preservation, and ischemia-reperfusion injury. Some mechanisms of reperfusion injury are now recognized; they include oxygen free radical (OFR), white blood cells activation, changes in calcium influx, alteration of microvascular blood flow, and sympathetic activation. The goal of this study was to assess the effects of two types of cardioplegia with long-term storage, either static or continuous perfusion, in 30 isolated sheep hearts as a model for heart transplantation. We examined myocardial function, histology, ischemic damage, and markers of oxidative stress. Two types of cardioplegia and storage conditions using a Langendorff reperfusion were studied in a combined approach: crystalloid (CP) [groups I and III] or cold oxygenated autologous blood (BC) [groups II and IV], immediate storage during 8h in profound hypothermia (groups I and II), or reperfused with crystalloid (group III), or blood cardioplegia (group IV). All perfusate samples were drawn from the coronary sinus. Lactate levels increased progressively in groups I, II, and IV, but not in group III, as no significant elevation was shown [90 min: 13.6+/-1.7 versus 5.2+/-1.0 mmol/L (P<0.01)]. Arrhythmias were more frequent when using BC (n=5) than CP (n=0). For plasma thiobarbituric acid-reactive substances (TBARS) levels a significant difference was found between group III and the other groups since 15 to 90 min (P<0.05). Vitamin E concentration decreased significantly from 5 min for groups II and IV, 15 min for group I, and 30 min for group III, with a significant difference between groups II and IV (P<0.05) but not between groups I and III. CP followed by a reperfusion with the same solution showed a significantly lower ischemic injury and OFR production, less frequent ventricular arrhythmias while stable hemodynamic parameters carried on. However, this protocol did not act on the early postoperative contractile function.

Acute, food-induced moderate elevation of plasma uric acid protects against hyperoxia-induced oxidative stress and increase in arterial stiffness in healthy humans

We examined the effects of acute, food-induced moderate increase of plasma uric acid (UA) on arterial stiffness and markers of oxidative damage in plasma in healthy males exposed to 100% normobaric oxygen. Acute elevation of plasma UA was induced by consumption of red wine, combination of ethanol and glycerol, or fructose. By using these beverages we were able to separate the effects of UA, wine polyphenols and ethanol. Water was used as a control beverage. Ten males randomly consumed test beverages in a cross-over design over the period of 4 weeks, one beverage per week. They breathed 100% O 2 between 60 th and 90 th min of the 4-h study protocol. Pulse wave augmentation index (AIx) at brachial and radial arteries, plasma antioxidant capacity (AOC), thiobarbituric acid-reactive substances (TBARS), lipid hydroperoxides (LOOH) assessed by xylenol orange method, UA and blood ethanol concentrations were determined before and 60, 90, 120, 150 and 240 min after beverage consumption. Consumption of the beverages did not affect the AIx, TBARS or LOOH values during 60 min before exposure to hyperoxia, while AOC and plasma UA increased except in the water group. Significant increase of AIx, plasma TBARS and LOOH, which occurred during 30 min of hyperoxia in the water group, was largely prevented in the groups that consumed red wine, glycerol + ethanol or fructose. In contrast to chronic hyperuricemia, generally considered as a risk factor for cardiovascular diseases and metabolic syndrome, acute increase of UA acts protectively against hyperoxia-induced oxidative stress and related increase of arterial stiffness in large peripheral arteries.

Assessment of Vascular Effects of Tamoxifen and Its Metabolites on the Rat Perfused Hindquarter Vascular Bed

Tamoxifen has been suggested to produce beneficial cardiovascular effects, although the mechanisms for these effects are not fully known. Moreover, although tamoxifen metabolites may exhibit 30-100 times higher potency than the parent drug, no previous study has compared the effects produced by tamoxifen and its metabolites on vascular function. Here, we assessed the vascular responses to acetylcholine and sodium nitroprusside on perfused hindquarter vascular bed of rats treated with tamoxifen or its main metabolites (N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen, and endoxifen) for 2 weeks. Plasma and whole-blood thiobarbituric acid reactive substances (TBARS) concentrations were determined using a fluorometric method. Plasma nitrite and NOx (nitrite + nitrate) concentrations were determined using an ozone-based chemiluminescence assay and Griess reaction, respectively. Treatment with tamoxifen reduced the responses to acetylcholine (pD(2) = 2.2 +/- 0.06 and 1.9 +/- 0.05 after vehicle and tamoxifen, respectively; P < 0.05), while its metabolites improved these responses (pD(2) = 2.5 +/- 0.04 after N-desmethyl-tamoxifen, 2.5 +/- 0.03 after 4-hydroxy-tamoxifen, and 2.6 +/- 0.08 after endoxifen; P < 0.01). Tamoxifen and its metabolites showed no effect on endothelial-independent responses to sodium nitroprusside (P > 0.05). While tamoxifen treatment resulted in significantly higher plasma and whole blood lipid peroxide levels (37% and 62%, respectively; both P < 0.05), its metabolites significantly decreased lipid peroxide levels (by approximately 50%; P < 0.05). While treatment with tamoxifen decreased the concentrations of markers of nitric oxide formation by approximately 50% (P < 0.05), tamoxifen metabolites had no effect on these parameters (P > 0.05). These results suggest that while tamoxifen produces detrimental effects, its metabolites produce counteracting beneficial effects on the vascular system and on nitric oxide/reactive oxygen species formation.