野山参与园参抗坏血酸-谷胱甘肽循环代谢差异的比较

目的通过比较野山参与园参在抗坏血酸-谷胱甘肽(AsA-GSH)循环中代谢相关酶活性及代谢物的量,探讨野山参与园参抗氧化能力差异。方法氮蓝四唑法测定超氧化物歧化酶(SOD)活性,高锰酸钾滴定法测定过氧化氢酶(CAT)活性,UV法测定抗氧化酶活性和抗氧化物的量,利用氨基酸自动分析仪检测谷氨酸、半胱氨酸、甘氨酸量。结果野山参中SOD、CAT活性高于园参,在AsA-GSH循环中野山参抗坏血酸过氧化物酶(APX)、单脱氢抗坏血酸还原酶(MDHAR)、谷胱甘肽还原酶(GR)等抗氧化酶活性均高于园参,谷胱甘肽(GSH)、抗坏血酸(AsA)、脱氢抗坏血酸(DHA)等抗氧化物的量有高于园参的趋势。比较谷胱甘肽合成前体的上游氨基酸(谷氨酸、半胱氨酸、甘氨酸)量,发现野山参亦高于园参,保障了AsA-GSH再循环的平衡。结论 AsA-GSH循环中关键抗氧化酶活性及抗氧化物量均为野山参高于园参,导致野山参抗氧化能力强于园参,为野山参与园参功效差异研究提供了理论依据。     

Nanoparticles for targeted delivery of antioxidant enzymes to the brain after cerebral ischemia and reperfusion injury

Stroke is one of the major causes of death and disability in the United States. After cerebral ischemia and reperfusion injury, the generation of reactive oxygen species (ROS) and reactive nitrogen species may contribute to the disease process through alterations in the structure of DNA, RNA, proteins, and lipids. We generated various nanoparticles (liposomes, polybutylcyanoacrylate (PBCA), or poly(lactide-co-glycolide) (PLGA)) that contained active superoxide dismutase (SOD) enzyme (4,000 to 20,000 U/kg) in the mouse model of cerebral ischemia and reperfusion injury to determine the impact of these molecules. In addition, the nanoparticles were untagged or tagged with nonselective antibodies or antibodies directed against the N-methyl-𝒟-aspartate (NMDA) receptor 1. The nanoparticles containing SOD protected primary neurons in vitro from oxygen-glucose deprivation (OGD) and limited the extent of apoptosis. The nanoparticles showed protection against ischemia and reperfusion injury when applied after injury with a 50% to 60% reduction in infarct volume, reduced inflammatory markers, and improved behavior in vivo. The targeted nanoparticles not only showed enhanced protection but also showed localization to the CA regions of the hippocampus. Nanoparticles alone were not effective in reducing infarct volume. These studies show that targeted nanoparticles containing protective factors may be viable candidates for the treatment of stroke.     

Anti-oxidants - a protective role in cardiovascular disease?

Established risk factors for cardiovascular disease (CVD), such as hypertension, smoking and diabetes mellitus, explain only some of the observed variation in clinical events. This has maintained interest in other nutritional and biochemical factors that might contribute to the underlying pathophysiology of CVD. All of these risk factors are associated with increased oxidative stress in the vessel wall, which may contribute to CVD by several mechanisms. Studies in animal models of CVD have suggested that natural and synthetic anti-oxidants can prevent the development of clinical end points. These observations have generated the hypothesis that anti-oxidant therapy might also prevent CVD in human populations. This has been supported by epidemiological studies showing a negative correlation between circulating concentrations or dietary intake of natural anti-oxidant vitamins and CVD event rate. Many studies have also demonstrated a beneficial effect of anti-oxidants on surrogate markers of CVD such as endothelial function and lipoprotein oxidation. However, the results of large prospective randomised controlled intervention trials, mostly involving vitamin E in patients at increased risk of CVD, have been disappointing and have failed to demonstrate the anticipated benefits. This paper will critically examine the evidence and try to offer some explanation for the apparent failure of animal and epidemiological data to translate into meaningful clinical benefits.     

Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndrome

Low-risk myelodysplastic syndrome (MDS) is characterized by cytopenia, mainly anemia, because of ineffective hematopoiesis. Some of the patients with ineffective erythropoiesis, with or without ring sideroblasts in their bone marrow, develop severe anemia requiring frequent blood transfusions and consequently develop iron overload. Excess free iron in cells catalyses the generation of reactive oxygen species (ROS) that cause cell and tissue damage. Using flow cytometry techniques, we compared the oxidative status of red blood cells (RBC), platelets and neutrophils in 14 MDS patients with those of normal donors. The results show that ROS were higher while reduced glutathione (GSH) was lower in their RBC and platelets compared with normal cells. In neutrophils, no difference was found in ROS, while the GSH levels were lower. A correlation (r = 0.6) was found between serum ferritin levels of the patients and the ROS in their RBC and platelets. The oxidative stress was ameliorated by a short incubation with the iron-chelators, the deferrioxamine and deferiprone or with antioxidants such as N-acetylcysteine, suggesting that MDS patients might benefit from treatment with iron-chelators and antioxidants.     

Current and emerging paradigms in the therapeutic management of atherosclerosis

Background: The pathogenesis of atherosclerosis lies in abnormalities in lipoprotein metabolism leading to pathological interactions with vessel walls and the release of inflammatory components, which further aggravate the disease condition. Objective: To elucidate current and emerging trends in drug discovery towards the development of new entities regulating lipoprotein metabolism and inflammatory components to combat the progression of atherosclerosis. Methods: Research/review articles in the public domain and press releases were employed. Results/conclusion: With the recent failure of torcetrapib and succinobucol, drug discovery and development efforts towards the treatment of atherosclerosis have received a big jolt and have been slowed down to certain extent. But this could be a starting point for several new mechanisms that are emerging to discover new drugs to combat the disease.     

Anti-oxidant therapy for the treatment of coronary artery disease

Coronary artery disease is the most common cause of death in developed countries. It may present in many different ways, but most frequently as a myocardial infarction, sudden death, angina or heart failure. Preventive measures in relation to coronary artery disease are particularly important because of its high incidence, high mortality and because most patients die outside hospital. Since the oxidation of low density lipoprotein cholesterol (LDL-C) is a critical early step in the process of atheroma formation, taking anti-oxidants to prevent LDL-C oxidation may prove a very effective means of reducing coronary artery disease mortality. However, the role of anti-oxidants in coronary artery disease prevention needs to be evaluated as part of an overall strategy that includes pharmacological and non-pharmacological measures, which are described in this review. In addition, a more structured and scientific approach to anti-oxidant therapy needs to be adopted. This requires that evidence for oxidative stress in a particular condition is obtained, the nature and severity determined and an appropriate anti-oxidant is administered, in an effective dose, which can be shown to correct the oxidative stress. When this is achieved, meaningful clinical trials should be possible, which will determine the place of anti-oxidant therapy for the specified condition.     

Inflammatory response in microvascular endothelium in sepsis: role of oxidants

Sepsis, as a severe systemic inflammatory response to bacterial infection, represents a major clinical problem. It is characterized by the excessive production of reactive oxygen species (ROS) both in the circulation and in the affected organs. The excessive generation of ROS inevitably leads to oxidative stress in the microvasculature and has been implicated as a causative event in a number of pathologies including sepsis. In this review, we focus on the role of oxidative and nitrosative stress during the early onset of sepsis. Changes in microvascular endothelial cells, the cell type that occurs in all organs, are discussed. The mechanisms underlying septic induction of oxidative and nitrosative stresses, the functional consequences of these stresses, and potential adjunct therapies for microvascular dysfunction in sepsis are identified.     

Paradoxically enhanced heart tolerance to ischaemia in type 1 diabetes and role of increased osmolarity

There is considerable controversy regarding the tolerance of diabetic hearts to ischaemia and the underlying mechanisms responsible for the increased heart tolerance to ischamia remain uncertain. In the present study, we observed, in vitro, type 1 diabetic heart responses to ischaemia and reperfusion at different degrees of hyperglycaemia. In addition, the possible role of increased osmolarity in cardioprotection due to hyperglycaemia was evaluated. Hearts from 3 week streptozocin-induced diabetic rats were isolated and perfused in a Langendorff apparatus and subjected to 30 min ischaemia and 30 min reperfusion. Cardiac function and the electrocardiogram were recorded. Myocardial content of osmolarity associated heat shock protein (hsp) 90, heme oxygenase (HO)-1 and anti-oxidant enzymes were determined in diabetic or hyperosmotic solution-perfused hearts using western blot. The hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG; 2 x 10(-7) mol/L) or the nitric oxide synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (1 x 10(-5) mol/L) was added to the perfusate to observe the effects of hsp90 inhibition and hsp90-associated endothelial NOS on ischaemic responses of diabetic hearts. Compared with normal control rats, diabetic hearts with severe hyperglycaemia (blood glucose > 20 mmol/L) showed markedly improved postischaemic heart function with fewer reperfusion arrhythmias. Mild hyperglycaemia (< 12 mmol/L) exhibited no significant cardioprotection. Elevated expression of hsp90 accompanied the enhanced resistance to ischaemia in diabetic hearts, which was abrogated by 17-AAG. In the presence of the NOS inhibitor, heart function was preserved, whereas reperfusion arrhythmias were increased in diabetes. Diabetic hearts also had markedly elevated HO-1 and catalase, with no significant change in superoxide dismutase. Hyperosmotic perfusion with glucose or mannitol also increased myocardial hsp90 and catalase. The present findings reveal that heart resistance to ischaemia is increased in short-term type 1 diabetes with severe hyperglycaemia. Elevated osmolarity caused by significant hyperglycaemia may contribute to the enhanced myocardial activity against oxidative injury during ischaemia and reperfusion.