beta-carotene and Reperfusion-Injury

Oxidative stress, favoring disease progression by a rapid degeneration of endothelial cell function is deeply involved in Systemic Sclerosis (SSc) pathogenesis. Raynaud's phenomenon (RP), present in 90% of patients with SSc, provoking frequent daily episodes of hypoxia-reperfusion injury, produces several episodes of free radicals-mediated endothelial derangement. These events results in a positive feedback effect of luminal narrowing and ischemia and therefore to the birth of a vicious cycle of oxygen free radicals (OFR) generation, leading to endothelial damage, intimal thickening and fibrosis. Thus ischemia and reperfusion are two criticals events that may induce oxidative stress and inactivation of antioxidant enzymes. In RP and SSc, a reduced concentration of ascorbic acid, alpha-tocopherol and beta-carotene as well as low values of Selenium have been reported. This antioxidative potential deficiency increases the propensity to oxidative stress. favoring the development of injury mediated by OFR. We reviewed several antioxidant compounds, aiming at their capacity of reverting endothelial dysfunction and damage, scavenging lipid peroxidation and reducing multiple episodes of hypoxia-reperfusion injury. In order to interrupt SSc vicious cycle, we propose a main strategy for SSc treatment by a supplementation of antioxidants and different kind of drugs with antioxidant property, such as Lazaroids, Resveratrol, Melatonin and Probucol.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Endothelium, Vascular; Humans; In Vitro Techniques; Melatonin; Nitric Oxide; Oxidative Stress; Pregnatrienes; Probucol; Raynaud Disease; Reactive Oxygen Species; Reperfusion Injury; Resveratrol; Scleroderma, Systemic; Selenium; Stilbenes; Vitamin E

Involvement of oxygen free radicals in ischemia-/reperfusion injury is based on measurement of increased products of lipid peroxidation after organ ischemia and restoration of blood flow during surgical operations and reperfusion of organ transplants. In cardiology inverse epidemiological correlations between plasma vitamin E levels and mortality due to ischemic heart disease, as well as beneficial effects of vitamin E on experimentally induced oxidative damage to the heart support the hypothesis, that vitamin E might have a protective role against myocardial ischemia-/reperfusion injury. In abdominal surgery efficiency of free radical scavengers has been intensively studied on animal models of hepatic ischemia and reperfusion. Examination of free radical scavengers and adenosine metabolites in liver tissue during hepatic ischemia revealed that vitamin E and glutathione levels as well as hepatic adenosine triphosphate levels are decreased during hepatic ischemia and reperfusion. The beneficial effects of alpha-tocopherol on hepatic viability and survival rate after ischemia and reperfusion demonstrated in these studies will be of great importance concerning further studies in organ preservation. In clinical kidney transplantation prevention of lipid peroxidation and improvement in kidney viability and function was demonstrated after infusion of a multivitamin cocktail in a prospective randomised study.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Humans; Reperfusion Injury; Vitamin A; Vitamin E; Vitamins

In summary, much evidence supports the formation of toxic oxygen metabolites in ischemic reperfused tissue. Tissues are equipped with both an intracellular and extracellular antioxidant defense system. The defense system can also be divided into enzymatic and nonenzymatic defenses. Important components of a nonenzymatic antioxidant include alpha-tocopherol, ascorbic acid, and beta-carotene as well as other compounds that can react with radicals to form less reactive products such as sulfur-containing amino acids. Extracellular fluid comprises a second line of defense against oxidant injury. These extracellular antioxidants include ceruloplasmin, albumin, transferrin, haptoglobin, and uric acid. The oxidant injury can potentially occur during ischemia and reperfusion due to (1) an excess production of oxygen free radicals, (2) a decrease in antioxidant defenses, or (3) both. Because antioxidants function by removing the toxic oxygen metabolites, they are generally highly effective in reducing ischemia-reperfusion injury.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Free Radicals; Humans; Ischemia; Oxidants; Reperfusion Injury; Vitamin E

Cilostazol improves walking distance in peripheral arterial disease (PAD) patients. The study objectives were to assess the effects of cilostazol on walking distance, followed by the additional assessment of cilostazol on exercise-induced ischaemia-reperfusion injury in such patients.. PAD patients were prospectively recruited to a double-blinded, placebo-controlled trial. Patients were randomised to receive either cilostazol 100mg or placebo twice a day. The primary end-point was an improvement in walking distance. Secondary end-points included the assessment of oxygen-derived free-radical generation, antioxidant consumption and other markers of the inflammatory cascade. Initial and absolute claudication distances (ICDs and ACDs, respectively) were measured on a treadmill. Inflammatory response was assessed before and 30 min post-exercise by measuring lipid hydroperoxide, ascorbate, alpha-tocopherol, beta-carotene, P-selectin, intracellular and vascular cell-adhesion molecules (I-CAM and V-CAM), thromboxane B(2) (TXB(2)), interleukin-6, interleukin-10, high-sensitive C-reactive protein (hsCRP), albumin-creatinine ratio (ACR) and urinary levels of p75TNF receptor. All tests were performed at baseline and 6 and 24 weeks.. One hundred and six PAD patients (of whom 73 were males) were recruited and successfully randomised from December 2004 to January 2006. Patients who received cilostazol demonstrated a more significant improvement in the mean percentage change from baseline in ACD (77.2% vs. 26.6% at 6 weeks, p=0.026 and 161.7% vs. 79.0% at 24 weeks, p=0.048) as compared to the placebo. Cilostazol reduced lipid hydroperoxide levels compared to a placebo-related increase before and after exercise (6 weeks: pre-exercise: -11.8% vs. +5.8%, p=0.003 and post-exercise: -12.3% vs. +13.9%, p=0.007 and 24 weeks: pre-exercise -15.5% vs. +12.0%, p=0.025 and post-exercise: -9.2% vs. +1.9%, p=0.028). beta-Carotene levels were significantly increased in the cilostazol group, compared to placebo, before exercise at 6 and 24 weeks (6 weeks: 34.5% vs. -7.4%, p=0.028; 24 weeks: 34.3% vs. 17.7%, p=0.048). Cilostazol also significantly reduced P-selectin, I-CAM and V-CAM levels at 24 weeks as compared to baseline (p<0.05). There was no difference between treatment groups for ascorbate, alpha-tocopherol, interleukin-6 and -10, hsCRP and p75TNF receptor levels.. Cilostazol significantly improves ACD, in addition to attenuating exercise-induced ischaemia-reperfusion injury, in PAD patients.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; alpha-Tocopherol; Ascorbate Oxidase; beta Carotene; C-Reactive Protein; Cilostazol; Creatinine; Double-Blind Method; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-10; Interleukin-6; Intermittent Claudication; Lipid Peroxides; Male; Middle Aged; P-Selectin; Prospective Studies; Receptors, Tumor Necrosis Factor; Reperfusion Injury; Tetrazoles; Thromboxane B2; Vascular Cell Adhesion Molecule-1; Vasodilator Agents; Walking

Beta-carotene is a well-known antioxidant and precursor of Vitamin A that has a preventative role in the oxidative damage process. Our aim was to investigate the possible preventive effects of beta-carotene on oxidative damage via experimental ischemia and ischemia-reperfusion models in rat ovaries.. A traumatic vascular clamps were used for 3h to induce ischemia (Group 2, 3, 4, 5, 6, 7). The clamps were then removed to allow reperfusion for 3h (Group 3, 6, 7). Sham-operated rats (Group 1) underwent laparotomy without the induction of ischemia/reperfusion injury. Real-Time-PCR was performed to determine IL-1-beta, IL-6 and iNOS expression levels. Histopathological (H&E) and immunohistochemical staining (NF-kβ p65) processes were then performed. Finally, SOD, GSH, and MDA levels were determined.. Intense hemorrhagic areas were observed in both the ischemia and ischemia/reperfusion groups, whereas minimal hemorrhage was observed in the treatment groups. The ischemia and ischemia/reperfusion groups exhibited extreme immunoreactivity, detected by NF-kβ p65 staining; this reactivity decreased after the application of beta-carotene. The expression of IL-1-beta, IL-6, and iNOS in the injury groups increased significantly, whereas a dose-dependent improvement was observed in the treatment groups. Finally, MDA levels increased significantly and SOD and GSH levels decreased drastically in the injury groups. However, these values obtained from I/R groups were normalized after beta-carotene treatment.. In this study, we demonstrated via molecular and biochemical parameters the protective effect of beta-carotene, which is a potent antioxidant, on the experimental ischemia-reperfusion model.

Topics: Animals; Antioxidants; beta Carotene; Drug Evaluation, Preclinical; Female; Glutathione; Interleukin-1beta; Interleukin-6; Ischemia; Malondialdehyde; NF-kappa B; Nitric Oxide Synthase Type II; Ovary; Rats, Wistar; Reperfusion Injury; Superoxide Dismutase

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.

Topics: Animals; Arrhythmias, Cardiac; beta Carotene; Blood Transfusion, Autologous; Cryopreservation; Glutathione Peroxidase; Graft Survival; Heart Arrest, Induced; Heart Transplantation; Lactic Acid; Lipid Peroxidation; Myocardial Contraction; Myocardium; Organ Preservation; Oxidative Stress; Potassium Compounds; Reperfusion Injury; Sheep; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Ventricular Pressure; Vitamin A; Vitamin E

The production of free radicals and reactive oxygen species are important factors contributing to ischemia/reperfusion injury. Thus scavenging of the excess free radicals can be an important therapeutic approach. Beta carotene, a carotenoid pigment has a potent antioxidant property. The present study examined the effect of beta carotene administration on the level of renal content of antioxidants and lipid peroxidation following ischemia/reperfusion injury in the rat kidney.. Male adult Wistar rats (250-300 g) were exposed to 45 min of renal ischemia followed by 4 h of reperfusion. Beta carotene (10, 30 and 100 mg kg(-1)) or vehicle was administered for 5 days prior to ischemia. Renal content of antioxidants and the level of lipid peroxidation were measured after the reperfusion period.. Our results showed that ischemia/reperfusion injury increased lipid peroxidation (p < 0.001) and decreased antioxidant (p < 0.001) in renal tissue. Pre-administration of beta carotene could attenuate these alterations (p < 0.05-p < 0.001), although not at all doses. Since beta carotene administration improved renal lipid peroxidation and antioxidants, it seems that beta carotene protects renal tissue against ischemia/reperfusion-induced oxidative damage.

Topics: Animals; Antioxidants; beta Carotene; Catalase; Glutathione Peroxidase; Kidney; Lipid Peroxidation; Male; Malondialdehyde; Rats; Rats, Wistar; Reperfusion Injury; Superoxide Dismutase; Vitamins

Renal ischemia/reperfusion injury is a major cause of acute renal failure. The production of free radicals and reactive oxygen species are important factors contributing to ischemia/reperfusion injury. Thus, scavenging of the excess free radicals can be an important therapeutic approach. The present study examined the protective effect of beta carotene against renal ischemia/reperfusion injury in rat. Male adult Wistar rats (250-300 g) were exposed to 45 min of renal ischemia followed by 4 h of reperfusion. Beta carotene (10, 30 and 100 mg kg(-1)) or vehicle was administered for 5 days prior to ischemia. Renal function was assessed by plasma and urinary analysis. Present results showed that ischemia/reperfusion injury increased (p < 0.05-p < 0.001) serum urea and creatinine levels, as well as urinary excretion of protein and calcium and fractional excretion of sodium, while decreased glomerular filtration rate and potassium excretion. However, alterations in these biochemical indices due to ischemia/reperfusion injury were attenuated by beta carotene pretreatment (p < 0.05-p < 0.001), although not by all doses. Since, beta carotene administration improved renal function, it seems that beta carotene protects renal tissue against ischemia/reperfusion-induced oxidative damage.

Topics: Animals; beta Carotene; Blood Urea Nitrogen; Calcium; Creatinine; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Potassium; Proteinuria; Random Allocation; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Sodium

An increasing number of reports suggest the involvement of oxidative stress in neurodegenerative diseases where the increased formation of reactive oxygen species (ROS) leads to neuronal damage and cell death. Dopamine may contribute to neurodegenerative disorders such as Parkinson's disease and ischemia/reperfusion-induced damage. Monoamine oxidase (MAO) enzyme (particularly MAO-B) is responsible for metabolizing dopamine and plays an important role in oxidative stress through altering the redox state of neuronal and glial cells. MAO participates in the generation of hydroxyl radicals during ischemia/reperfusion. This suggests the possible use of MAO inhibitors as neuroprotective agents for treating ischemic injury. The protective effect of deprenyl (N-methyl-N-(1-methyl-2-phenyl-ethyl)-prop-2-yn-1-amine, CAS 14611-51-9) (2 and 10 mg/kg), a MAO-B inhibitor, and beta-carotene (10 and 20 mg/kg), a natural antioxidant, was examined in a rat model of cerebral ischemia. Ischemia was induced in rats by bilateral carotid artery occlusion for 1 h followed by declamping for another hour. The effect of the drugs on the brain activity of lactate dehydrogenase (LDH) and some of the oxidative stress biomarkers such as brain activity of superoxide dismutase (SOD) and catalase (CAT) enzymes and brain malondialdehyde (MDA) content was determined. In addition, the content of catecholamines such as noradrenaline (NA) and dopamine (DA) was determined. Deprenyl decreased the ischemia-induced elevation of LDH activity and MDA content and normalized the SOD activity. In addition, deprenyl increased the CAT activity back to normal, and increased the noradrenaline and dopamine content in the brain of rats. Beta-carotene administration ameliorated the effect of ischemia followed by reperfusion (I/R) demonstrated as decreasing the LDH activity and MDA content and by increasing the SOD activity. The drug also increased CAT activity in the brain of rats. However, beta-carotene did not alter the NA and DA content. These results indicate that deprenyl protected the rat brains against the ischemia-induced oxidative damage, an effect which might be explained through multiple mechanisms, possibly due to reduction of dopamine catabolism with a subsequent increased activity on dopaminergic D2 receptors and suppressing the action of ROS as well.

Topics: Animals; Antioxidants; beta Carotene; Brain Chemistry; Brain Ischemia; Catalase; Dose-Response Relationship, Drug; L-Lactate Dehydrogenase; Male; Malondialdehyde; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neurons; Norepinephrine; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Selegiline; Superoxide Dismutase

Heme oxygenase (HO) catalyzes the rate-limiting enzymatic step of heme degradation and regulates the cellular heme content. Gene expression of the inducible isoform of HO, HO-1, is upregulated in response to various oxidative stress stimuli. To investigate the regulatory role of anoxia and reoxygenation (A/R) on hepatic HO-1 gene expression, primary cultures of rat hepatocytes were exposed after an anoxia of 4 hr to normal oxygen tension for various lengths of time. For comparison, gene expression of the noninducible HO isoform, HO-2, and that of the heat-shock protein 70 (HSP70) were determined. During reoxygenation, a marked increase of HO-1 and HSP70 steady-state mRNA levels was observed, whereas no alteration of HO-2 mRNA levels occurred. Corresponding to HO-1 mRNA, an increase of HO-1 protein expression was determined by Western blot analysis. The anoxia-dependent induction of HO-1 was prevented by pretreatment with the transcription inhibitor, actinomycin D, but not by the protein synthesis inhibitor, cycloheximide, suggesting a transcriptional regulatory mechanism. After exposure of hepatocytes to anoxia, the relative levels of oxidized glutathione increased within the first 40 min of reoxygenation. Pretreament of cell cultures with the antioxidant agents, beta-carotene and allopurinol, before exposure to A/R led to a marked decrease of HO-1 and HSP70 mRNA expression during reoxygenation. An even more pronounced reduction of mRNA expression was observed after exposure to desferrioxamine. Taken together, the data demonstrate that HO-1 gene expression in rat hepatocyte cultures after A/R is upregulated by a transcriptional mechanism that may be, in part, mediated via the generation of ROS and the glutathione system.

Topics: Allopurinol; Animals; Antioxidants; beta Carotene; Cell Hypoxia; Cells, Cultured; Cycloheximide; Dactinomycin; Deferoxamine; Free Radical Scavengers; Gene Expression Regulation, Enzymologic; Glutathione; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Hepatocytes; HSP70 Heat-Shock Proteins; Iron Chelating Agents; Male; Oxygen; Protein Synthesis Inhibitors; Rats; Rats, Wistar; Reperfusion Injury

Endothelial injury occurs as a result of oxygen free radical production after ischemia and reperfusion of transplanted livers, causing hemodynamic disturbance. Patients with chronic liver disease generally have low levels of fat-soluble vitamins, which have important antioxidant roles. We therefore assessed circulating levels of the antioxidants vitamin A, vitamin E, beta-carotene and lycopene, indices of lipid peroxidation and hemodynamic changes during elective orthotopic liver transplantation in 12 patients. We found that initial antioxidant levels were severely depleted compared with healthy subjects, and in some patients carotene and lycopene levels were undetectable. Increased lipid peroxidation was also evident, as shown by thiobarbituric acid-reactive substances. On reperfusion of the liver graft, vitamin A and E levels fell (p < 0.01) and were associated with decreases in systemic vascular resistance (p < 0.02). These data show that patients undergoing liver transplant have lowered antioxidant defenses and evidence of free radical damage, which compound the additional insult of reperfusion injury. Antioxidant therapy in these patients before transplantation may ameliorate the effects of reperfusion.

Topics: Adult; Aged; beta Carotene; Blood Pressure; Cardiac Output; Carotenoids; Female; Hemodynamics; Humans; Lipid Peroxidation; Liver Failure; Liver Transplantation; Lycopene; Male; Middle Aged; Reperfusion Injury; Vascular Resistance; Vitamin A; Vitamin E; Vitamins