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Resveratrol improves hepatic insulin signaling and reduces the inflammatory response in streptozotocin-induced diabetes

Diabetes mellitus is a heterogeneous metabolic disorder essentially characterized by deficiency of insulin secretion, insulin receptor or post-receptor events. This study aims to investigate the effects of resveratrol administration on the metabolic characteristics, hepatic functions, histopathological features and insulin signaling pathway components in streptozotocin induced diabetes. Male Wistar rats were randomly divided into four groups: (1) control/vehicle; (2) control/20mg/kg resveratrol; (3) diabetic/vehicle; and (4) diabetic/20mg/kg resveratrol. Histopathological examinations were carried out to reveal hepatic tissue damage and inflammation. In addition to hepatic glucose, lipid, insulin, ALT, AST, resistin and XOD contents, gene and protein expressions of insulin signaling pathway components such as insulin Rβ, IRS-1, IRS-2, eNOS, PI3K, Akt, and FOXO3a were analyzed by qRT-PCR and Western blot. The rats in the diabetes group had significantly lower terminal body weight and hepatic insulin level, but significantly higher hepatic glucose, total cholesterol, triglyceride and resistin concentrations. Diabetes triggered the inflammatory process in the liver tissues that was evidenced by histopathological deformations and increase in the hepatic ALT and AST levels. Hepatic inflammation was considerably associated with insulin signaling pathway ever since a significant down-regulation of insulin signaling components; IRS-1, IRS-2, PI3K, Akt and mTOR have been identified in the diabetic group. To some extent, resveratrol treatment reversed the diabetes-induced changes in the liver tissues. Taken together, resveratrol partly improved hepatic dysfunction induced by diabetes. This may be due to the healing activity of resveratrol on insulin signaling pathway, resistin levels and hepatic glucose-lipid contents.

Dietary Fructose Activates Insulin Signaling and Inflammation in Adipose Tissue: Modulatory Role of Resveratrol

The effects of high-fructose diet on adipose tissue insulin signaling and inflammatory process have been poorly documented. In this study, we examined the influences of long-term fructose intake and resveratrol supplementation on the expression of genes involved in insulin signaling and the levels of inflammatory cytokines and sex hormones in the white adipose tissues of male and female rats. Consumption of high-fructose diet for 24 weeks increased the expression of genes involved in insulin signaling including IR, IRS-1, IRS-2, Akt, PI3K, eNOS, mTOR, and PPARγ, despite induction of proinflammatory markers, iNOS, TNFα, IL-1β, IL-18, MDA, and ALT, as well as anti-inflammatory factors, IL-10 and Nrf2 in adipose tissues from males and females. Total and free testosterone concentrations of adipose tissues were impaired in males but increased in females, although there were no changes in their blood levels. Resveratrol supplementation markedly restored the levels of MDA, IL6, IL-10, and IL-18, as well as iNOS, Nrf2, and PI3K mRNA, in adipose tissues of both genders. Dietary fructose activates both insulin signaling and inflammatory pathway in the adipose tissues of male and female rats proposing no correlation between the tissue insulin signaling and inflammation. Resveratrol has partly modulatory effects on fructose-induced changes.

Resveratrol Ameliorates the Components of Hepatic Inflammation and Apoptosis in a Rat Model of Streptozotocin-Induced Diabetes.

Preclinical Research

Dietary Fructose-Induced Hepatic Injury in Male and Female Rats: Influence of Resveratrol.

Purpose: Relatively little is known about gender-dependent susceptibility to hepatic injury induced by nutritional factors. In the current study, we investigated dietary fructose-induced hepatic degeneration and roles of endothelial nitric oxide synthase (eNOS), insulin receptor (IRβ) and substrate-1 (IRS-1) expressions in association with inflammatory markers in male and female rats. Moreover, we examined potential effect of resveratrol on fructose-induced changes. Methods: Male and female rats were divided into 4 groups as control, resveratrol, fructose and resveratrol plus fructose. All rats were fed with a standard diet with or without resveratrol (500 mg/kg). Fructose was given as 10% in drinking waterfor 24 weeks. Results: Long-term dietary fructose caused parenchymal degeneration and hyperemia in association with impaired eNOS mRNA/protein expressions in liver of male and female rats. This dietary intervention also led to increases in hepatic triglyceride content, TNFα and IL-1β levels in both genders. Gender-related differences to consequence of fructose consumption were not obvious. Resveratrol supplementation markedly attenuated hepatic degeneration, hyperemia and triglyceride content in association with reduced TNFα and IL-1β levels, but enhanced IRβ mRNA and IRS-1 protein, in male and female rats upon fructose feeding. Conclusion: Long-term dietary fructose causes hepatic degeneration possibly via a decrease in eNOS, but increase in TNFα and IL-1β, in both genders. Resveratrol supplementation improved fructose-induced hepatic injury.

Effects of N-acetyl cysteine on renal functions evaluated by blood neutrophil gelatinase-associated lipocalin levels in geriatric patients undergoing coronary artery bypass grafting

Objective: Recent conflicting studies on the renal effects of N-acetyl cysteine (NAC) after cardiac surgery have been published. The aim of this study was to evaluate the renal effects of NAC using neutrophil gelatinase-associated lipocalin (NGAL) blood levels in elderly patients undergoing coronary artery bypass grafting (CABG). Methods: This randomized, double-blinded, placebo-controlled study was conducted among geriatric patients (>65 years) scheduled to undergo CABG. A total of 60 consecutive patients were randomly assigned to 2 groups. The first group received I.V. NAC (n=30) and the second group received placebo (n=30) at induction of anesthesia and then for 20 h. NGAL values were determined and conventional renal function tests were performed. Statistical analysis was performed using SPSS 17.0 (IL, Chicago, USA). A p value of <0.05 was considered statistically significant Results: Plasma creatinine levels at 24 h postoperatively were significantly higher in the placebo group than in the NAC group (1.41±0.63 vs. 1.13±0.35; p<0.05). The mean serum NGAL levels at 3 h postoperatively were higher in the placebo group than in the NAC group (104.94±30.51 vs. 87.82±25.18; p<0.05). NGAL levels were similar between the groups at all other measurement time points. Plasma creatinine levels of ≥1.5 mg/dL or >25% of the baseline value at any time during the study period were observed in 27% of patients in the NAC group and 37% of patients in the placebo group; the difference was statistically significant (p<0.05). Conclusion: In the present study, we found that I.V. NAC infusion in elderly patients undergoing CABG reduced the incidence of acute kidney injury as determined by blood NGAL and creatinine levels.

Serum vitamin B-12 in children presenting with vasovagal syncope

BACKGROUND AND OBJECTIVES The present study aims to determine the serum vitamin B-12 in children presenting with vasovagal syncope. METHODS AND STUDY DESIGN This is a prospective review of 160 children presenting with vasovagal syncope. Subgroup analysis was done based on the results of head up tilt test. RESULTS Head up tilt test gave positive results in 80 children and yielded negative results in the remaining 80 children. The tilt test positive children had significantly lower thyroid stimulating hormone concentrations (p=0.06), total iron binding capacity (p=0.04) and serum vitamin B-12 (p=0.01). The prevalence of vitamin B-12 deficiency was significantly higher in the tilt positive group (80% vs 52.5%, p=0.001). Out of 80 children with positive tilt test, 8 children (10%) showed cardioinhibitory response, 22 children (27.5%) demonstrated a vasodepressor response, 24 children (30%) displayed mixed response and 26 children (32.5%) had the postural orthostatic tachycardia syndrome. Erythrocyte sedimentation rate was significantly lower in the mixed response group than in the vasodepressor group (6.2±0.8 mm/h vs 14.3±2.5 mm/h, p=0.001). Serum vitamin B-12 was significantly lower in the postural orthostatic tachycardia syndrome (POTS) group than in the vasodepressor group (240.8±38.2 pg/mL vs 392.7±27.1 pg/mL, p=0.001). The prevalence of vitamin B-12 deficiency was significantly higher in the POTS group than in the vasodepressor group (92.3% vs 45.5%, p=0.001). CONCLUSIONS Vitamin B-12 deficiency causes reduction in myelinization, deceleration in nerve conduction and elevation in serum concentrations of noradrenaline. These factors may contribute to the impairment of autonomic functions which are involved in the pathogenesis of vasovagal syncope.

Effects of resveratrol on diabetes-induced vascular tissue damage and inflammation in male rats

Abstract Objective: The present study aims to investigate the short-term effects of resveratrol on histopathological characteristics and inflammatory cytokines of the heart and thoracic aorta tissues in animal models of streptozotocin (STZ)-induced diabetes. Methods: Male Wistar rats were randomly divided into four groups; (1) control/vehicle, (2) control/20 mg/kg resveratrol, (3) diabetic/vehicle, (4) diabetic/20 mg/kg resveratrol. Heart and thoracic aorta were examined histopathologically and the levels of interleukin (IL)-1β, IL-18 and tissue necrosis factor (TNF)-α were analyzed by ELISA. Malondialdehyde (MDA) contents were determined with HPLC. Results: Diabetes group had significantly higher vascular MDA content (p<0.05) as compared with the control and resveratrol treated groups. Resveratrol significantly reduced vascular MDA level in diabetic animals (p<0.05). Significant elevation in IL-1β and TNF-α contents in thoracic aorta and IL-18 contents in cardiac and arterial tissues with diabetes were almost normalized with resveratrol treatment. Additionally, diabetic animals demonstrated significant endothelial damage, irregularities in smooth muscle fibers and degeneration of elastic fibers in thoracic aortas together with significant irregularities and hypertrophy in cardiac muscle fibers. Resveratrol significantly improved most of these histopathological alterations. Conclusion: Four-week-long intraperitoneal administration of resveratrol may restore the diabetes related inflammation and oxidative stress within the cardiovascular system. Özet Amaç: Bu çalışma, streptozotocin (STZ) ile oluşturulmuş diyabetin hayvan modellerinde resveratrolün kalp ve damar dokularında histopatolojik özellikler ve inflamatuar sitokinler üzerine kısa süreli etkilerini araştırmayı amaçlamıştır. Metod: Erkek Wistar sıçanları (1) kontrol, (2) kontrol/20 mg/kg resveratrol, (3) diyabetik, (4) diyabetik/20 mg/kg resveratrol olmak üzere dört gruba ayrılmıştır. Kalp ve damar dokuları histopatolojik olarak incelenmiştir. Buna ilave olarak, interleukin (IL)-1β, IL-18 ve doku nekroz faktör (TNF)-α düzeyleri ELISA yöntemiyle, malondialdehit (MDA) miktarı ise HPLC ile belirlenmiştir. Bulgular: Diyabet grubunda vasküler MDA miktarı kontrol ve resveratrol gruplarına göre anlamlı ölçüde (p<0,05) yükselmiştir. Diyabetik hayvanlarda resveratrol, vasküler MDA düzeylerini anlamlı derecede (p<0,05) düşürmüştür. Torasik aorta dokularındaki IL-1β ve TNF-α düzeylerinde meydana gelen anlamlı artış, kardiyak ve arterial dokularındaki IL-18 düzeylerindeki yükseliş, resveratrol uygulamasıyla büyük ölçüde normalize edilmiştir. Buna ilave olarak diyabetik hayvanların torasik aortlarında anlamlı ölçüde endotel hasar, düz kas liflerinde düzensizlikler ve elastik liflerinde dejenerasyon gösterilmiştir. Ayrıca kardiyak kas liflerinde belirginleşen düzensizlikler ve hipertropi gösterilmiştir. Diyabetik hayvanlara resveratrol tedavisi, bu olumsuz değişiklikleri kısmi olarak iyileştirmiştir. Sonuç: Dört hafta boyunca intraperitonal yoldan uygulanan resveratrol, kardiyovasküler sistemde diyabetle meydana gelen inflamasyon ve oksidatif stresi azaltacak potansiyele sahiptir.

Does the use of Bispecteral Index reduce the oxidative stress in Endoscopic Retrograde Pancreoticocolangiography

Background: Endoscopic Retrograde Pancreoticocolangiography (ERCP) is performed for resolving cholestasis by sphincterotomy and/or stone extraction and is done with deep sedation or general anesthesia.