Lipopolysaccharide-induced VEGF production and ambient oxidative stress in type 2 diabetes

Context Oxidative stress is implicated in the development of microvascular disease and is associated with an upregulation of vascular endothelial growth factor (VEGF) which is pathogenetically linked to microvascular complications of diabetes. Patients of African origin have an increased susceptibility to microvascular kidney disease compared with Caucasians, the reasons and the mechanisms that contributes to this vulnerability are unclear. Objectives Primary) Investigate whether there are ethnic differences in Lipopolysaccharide induced monocyte VEGF production in whole blood cell cultures. Secondary) whether stimulated VEGF production is related to prevailing oxidative stress assessed by plasma lipid hydroperoxides (LOOH) and α-Tocopherol. Design and Setting Cross sectional study at a secondary care centre in North London, UK, serving an inner-city community of 154,000 adults. Patients African-Caribbean and Caucasian patients with type 2 diabetes (n=52) Results Lipopolysaccharide induced production of VEGF in whole blood cultures (61.8[31.9] pg/mL to 78.4[36.0] pg/mL; p<0.001) that correlated positively with LOOH levels (r=0.3, P=0.04) and was significantly higher in African-Caribbean than Caucasian type 2 diabetes patients (404 [207.5] vs 268.8 [137.0] pg/mL X109/L monocytes; P=0.018). Plasma α-Tocopherol concentration was higher in Caucasian patients (40.3[18.3] vs 30.0[9.6] µmol/L; p=0.04) compared to African-Caribbeans. Conclusions This study suggests that the redox environment influences VEGF production in response to proinflammatory stimuli in type 2 diabetes. The differential responsiveness by ethnic origin may be of relevance in the variations in susceptibility to the long-term microvascular complications

Isoprostane in systemic sclerosis: a systematic review and meta-analysis

Objectives: To further the knowledge of oxidative stress in systemic sclerosis (SSc), we performed a systematic review and meta-analysis on studies measuring isoprostane, a vasoactive agent deriving from arachidonic acid and implicated in the vasculopathy of SSc. Methods: Systematic search following the PRISMA guidelines in PubMed and EMBASE between January-1990/December-2017 using the terms: oxidative stress, isoprostane, systemic sclerosis and scleroderma. Results: After the screening process, 8 studies including 240 SSc patients and 192 controls were included in the systematic review and meta-analysis, 6 investigating urinary and 2 serum isoprostane: random effect meta-analysis revealed isoprostane overgeneration in SSc (p &lt;.001) with wide heterogeneity (I 2 = 75%). Subgroup analysis on urinary isoprostane favoured excess excretion in SSc (p =.009) with slightly lower heterogeneity (I 2 = 67%); further subgroup analysis according to unit of measurement revealed no increased isoprostane excretion when expressed as pg/mg creatinine but increased when expressed as pmol/mmol creatinine (p =.05) with medium heterogeneity (I 2 = 32%). Subgroup analysis on serum isoprostane favoured overproduction in SSc (p &lt;.0001) with no heterogeneity. Conclusion: There is some evidence for isoprostane overgeneration in SSc that confirms the occurrence of oxidative stress in this setting: further prospective studies with specified outcomes are needed to evaluate the prognostic value of this functional biomarker

Oxidative/nitrative stress in the pathogenesis of systemic sclerosis: are antioxidants beneficial?

Systemic sclerosis (SSc) is a multisystem autoimmune disease: characterised from the clinical side by progressive vasculopathy and fibrosis of the skin and different organs and from the biochemical side by fibroblast deregulation with excessive production of collagen and increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). The latter contributes to an overproduction of reactive oxygen species that through an autocrine loop maintains NOX4 in a state of activation. Reactive oxygen and nitrogen species are implicated in the origin and perpetuation of several clinical manifestations of SSc having vascular damage in common; attempts to dampen oxidative and nitrative stress through different agents with antioxidant properties have not translated into a sustained clinical benefit. Objective of this narrative review is to describe the origin and clinical implications of oxidative and nitrative stress in SSc, with particular focus on the central role of NOX4 and its interactions, to re-evaluate the antioxidant approaches so far used to limit disease progression, to appraise the complexity of antioxidant treatment and to touch on novel pathways elements of which may represent specific treatment targets in the not so distant future

Integral Kinetic Model for Studying Quercetin Degradation and Oxidation as Affected by Cholesterol During Heating

The degradation and oxidation of quercetin, as affected by cholesterol during heating at 150 °C, was kinetically studied using non-linear regression models. Both TLC and HPLC were used to monitor the changes of quercetin, cholesterol and cholesterol oxidation products (COPs) during heating. The formation of COPs, including triol, 7-keto, 7α-OH and 7β-OH, was completely inhibited during the initial 30 minute heating period in the presence of 0.02% quercetin, accompanied by reduction in cholesterol peroxidation and degradation. However, the quercetin degradation or oxidation proceeded fast, with the rate constants (h−1) in the presence of nitrogen, oxygen and the combination of oxygen and cholesterol being 0.253, 0.868 and 7.17, respectively. When cholesterol and quercetin were heated together, the rate constants (h−1) of cholesterol peroxidation, epoxidation and degradation were 1.8 × 10−4, 0.016 and 0.19, respectively. The correlation coefficients (r2) for all the oxidative and degradation reactions ranged from 0.82–0.99. The kinetic models developed in this study may be used to predict the degradation and oxidation of quercetin as affected by cholesterol during heating

Alterations in the blood glucose, serum lipids and renal oxidative stress in diabetic rats by supplementation of onion (Allium cepa. Linn)

This study examined the anti-diabetic effect of onion (Allium cepa. Linn) in the streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into normal rats fed control diet or supplemented with onion powder (7% w/w) and diabetic rats fed control diet or supplemented with onion powder. Diabetes was induced by a single injection of STZ (60 mg/kg, ip) in citrate buffer. The animals were fed each of the experimental diet for 5 weeks. Blood glucose levels of rats supplemented with onion were lower than those of rats fed control diet in the diabetic rats. Onion also decreased the total serum lipid, triglyceride, and atherogenic index and increased HDL-cholesterol/total cholesterol ratio in the diabetic rats. Glutathione peroxidase, glutathione reductase and glutathione S-transferase activities were high in the diabetic rats compared to normal rats and reverted to near-control values by onion. These results indicate that onion decreased blood glucose, serum lipid levels and reduced renal oxidative stress in STZ-induced diabetic rats and this effect might exert the anti-diabetic effect of onion

Influence of antioxidant (L- ascorbic acid) on tolbutamide induced hypoglycaemia/antihyperglycaemia in normal and diabetic rats

BACKGROUND: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia. Increased oxidative stress and decreased antioxidant levels are the leading cause of diabetes and diabetic complications. So it is felt that supplementation of antioxidants may be useful in controlling the glucose levels and to postpone the occurrence of diabetic complications. The objective of our study is to find the influence of antioxidant supplementation (L-ascorbic acid) on tolbutamide activity in normal and diabetic rats. METHODS: L- ascorbic acid/tolbutamide/L-ascorbic acid + tolbutamide were administered orally to 3 different groups of albino rats of either sex in normal and diabetic condition. Blood samples were collected from retro-orbital puncture at different time intervals and were analyzed for blood glucose by GOD-POD method. Diabetes was induced by alloxan 100 mg/kg body weight administered by I.P route. RESULTS: L-ascorbic acid/ tolbutamide produced hypoglycaemic activity in a dose dependant manner in normal and diabetic condition. In the presence of L-ascorbic acid, tolbuatmide produced early onset of action and maintained for longer period compared to tolbutamide matching control. CONCLUSION: Supplementation of antioxidants like L-ascorbic acid was found to improve tolbutamide response in normal and diabetic rats