Long-term N-acetylcysteine and L-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes.

Department of Internal Medicine, University of Torino, Corso Dogliotti 14, I-10121 Torino, Italy.
Diabetes care (Impact Factor: 7.74). 05/2008; 31(5):940-4. DOI: 10.2337/dc07-2251
Source: PubMed

ABSTRACT Reactive oxygen and nitric oxide (NO) have recently been considered to be involved in the cardiovascular complications of patients with type 2 diabetes, as NO is thought to lose its beneficial physiological effects in the presence of oxygen radicals. For this reason, we tested the effects of l-arginine (ARG) and N-acetylcysteine (NAC) administration in increasing NO bioavailability by reducing free radical formation.
A double-blind study was performed on 24 male patients with type 2 diabetes and hypertension divided into two groups of 12 patients that randomly received either an oral supplementation of placebo or NAC + ARG for 6 months.
The NAC + ARG treatment caused a reduction of both systolic (P < 0.05) and diastolic (P < 0.05) mean arterial blood pressure, total cholesterol (P < 0.01), LDL cholesterol (P < 0.005), oxidized LDL (P < 0.05), high-sensitive C-reactive protein (P < 0.05), intracellular adhesion molecule (P < 0.05), vascular cell adhesion molecule (P < 0.01), nitrotyrosine (P < 0.01), fibrinogen (P < 0.01), and plasminogen activator inhibitor-1 (P < 0.05), and an improvement of the intima-media thickness during endothelial postischemic vasodilation (P < 0.02). HDL cholesterol increased (P < 0.05). No changes in other parameters studied were observed.
NAC + ARG administration seems to be a potential well-tolerated antiatherogenic therapy because it improves endothelial function in hypertensive patients with type 2 diabetes by improving NO bioavailability via reduction of oxidative stress and increase of NO production. Our study's results give prominence to its potential use in primary and secondary cardiovascular prevention in these patients.

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    ABSTRACT: Background/Objectives:Vitamin D, L-cysteine (LC) and glutathione (GSH) levels are lower in the blood of diabetic patients. This study examined the hypothesis that the levels of vitamin D and LC correlate with those of GSH in the blood of type 2 diabetic patients (T2D), and that vitamin D and LC upregulate glutamate-cysteine ligase (GCLC), which catalyzes GSH biosynthesis, in cultured monocytes.Subjects/Methods:Fasting blood was obtained after written informed consent from T2D (n=79) and healthy controls (n=22). U937 monocytes were pretreated with 1,25 (OH)2 vitamin D (0-25 nM) or LC (0-500 μM) for 24 h and then exposed to control or high glucose (25 mM) for 4 h.Results:Plasma levels of vitamin D, LC, GSH and GCLC protein were significantly lower in T2D versus those in age-matched healthy controls. Multiple linear regression analyses and adjustment for body weight showed a significant positive correlation between plasma levels of vitamin D (r=0.26, P=0.05) and LC (r=0.81, P=0.001) and that of GSH, and between LC and vitamin D (r=0.27, P=0.045) levels. Plasma levels of GSH (r=-0.34, P=0.01) and LC (r=-0.33, r=0.01) showed a negative correlation with triglyceride levels. Vitamin D correlated inversely with HbA1C (-0.30, P=0.01) and homeostatic model assessment insulin resistance (r=-0.31, P=0.03), which showed a significant positive correlation with triglycerides (r=0.44, P=0.001) in T2D. Cell culture studies demonstrate that supplementation with vitamin D and LC significantly increased GCLC expression and GSH formation in control and high-glucose-treated monocytes.Conclusions:This study suggests a positive relationship between the concentrations of the micronutrients vitamin D and LC and that of GSH. Some of the beneficial effects of vitamin D and LC supplementation may be mediated by an increase in the levels of GSH and a decrease in triglyceride levels in T2D patients.European Journal of Clinical Nutrition advance online publication, 25 June 2014; doi:10.1038/ejcn.2014.114.
    European Journal of Clinical Nutrition 06/2014; · 2.95 Impact Factor
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    ABSTRACT: Type 2 diabetic patients have increased susceptibility to melioidosis, an infectious disease caused by Burkholderia pseudomallei. We had previously shown that peripheral blood mononuclear cells (PBMCs) from diabetic patients with poor glycemic control had a defective IL-12 and IFNγ response to B. pseudomallei infection, resulting in poor intracellular bacterial control. The impaired IL-12 response was due to glutathione (GSH) deficiency characterized by a low reduced to oxidized glutathione ratio (GSH ratio) and could be restored by the addition of reduced GSH to the infected cells. Our goal is to determine whether N-acetyl cysteine (NAC, a GSH pro-drug) supplementation in diabetic patients could improve their immune control of B. pseudomallei. Type 2 diabetic patients with poor glycemic control were given oral supplementation of NAC for six weeks at 1200mg daily. Their PBMCs and subsets of immune cells showed a significant increase in free GSH concentration. However, the GSH ratio, IL-12 and IFNγ production, and intracellular bacterial killing upon ex-vivo infection did not improve. Thus, oral NAC supplementation in diabetic patients is sufficient to increase intracellular GSH content in blood cells. However, modulating the free GSH content is not sufficient to improve infection outcome as it is the GSH ratio that regulates the IL-12 response in monocytes.
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    ABSTRACT: Background & Aim Dyslipidemia is involved with in development of cardiovascular diseases and obesity, exercise is recommended as a successful intervention. Dietary L-arginine (L-arg) supplementation may improve in lipid metabolism. However, these combined strategies on lipid profile were not tested yet. This study examines the effects of short term of L-arg supplementation and acute resistance exercise (AREX) on the blood lipid profile and inflammatory proteins in overweight men. Methods Seven overweight men, 46±5 yrs, body weight 93.1±12.0 Kg and BMI 31.7±3 Kg/m2, participated in a randomized, double-blind and crossover study, distributed into exercise groups, based on the supplementation (6 g/ day of placebo or Arginine for 7 days). Supplementation periods were separated by 7-days of wash-out. The AREX was comprised of eight exercises, with an exercise intensity of 60% 1RM. The glucose, lipid profile (NEFA, triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol) and inflammatory proteins [plasminogen activator inhibitor-1 (PAI-1) and adiponectin] were determined at rest, immediately, after exercise and 1 hour after exercise sessions. Results Triglycerides, total cholesterol, and adiponectin levels not showed time-dependent changes under the different conditions. LDL cholesterol and NEFA levels decreased after 1 hour recovery periods when compared to rest periods only in L-arg supplementation group (P< 0.05). PAI-1 was reduced and HDL cholesterol exhibits increases immediately after AREX and 1 hour recovery periods when compared with rest periods in both groups (P< 0.05). Conclusion These results indicate that L-arg supplementation can potentiate the effects of exercise inducing changes in the LDL cholesterol and NEFA levels.
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