N-Acetyl-l-Cysteine Supplement in Early Life or Adulthood Reduces Progression of Diabetes in Nonobese Diabetic Mice

Abstract

Background Oxidative stress contributes to the pathologic process leading to the development, progression, and complications of type 1 diabetes (T1D). Objective The aim of this study was to investigate the effect of the antioxidant N-acetyl-l-cysteine (NAC), supplemented during early life or adulthood on the development of T1D. Methods NAC was administered to nonobese diabetic (NOD) female mice during pregnancy and lactation, and the development of diabetes was followed in offspring. In an additional set of experiments, offspring of untreated mice were given NAC during adulthood, and the development of T1D was followed. Morbidity rate, insulitis and serum cytokines were measured in the 2 sets of experiments. In addition, markers of oxidative stress, glutathione, lipid peroxidation, total antioxidant capacity and activity of antioxidant enzymes, were followed. Results Morbidity rate was reduced in both treatment protocols. A decrease in interferon γ, tumor necrosis factor α, interleukin 1α, and other type 1 diabetes-associated proinflammatory cytokines was found in mice supplemented with NAC in adulthood or during early life compared with control NOD mice. The severity of insulitis was higher in control NOD mice than in treated groups. NAC administration significantly reduced oxidative stress, as determined by reduced lipid peroxidation and increased total antioxidant capacity in serum and pancreas of mice treated in early life or in adulthood and increased pancreatic glutathione when administrated in adulthood. The activity of antioxidant enzymes was not affected in mice given NAC in adulthood, whereas an increase in the activity of superoxide dismutase and catalase was demonstrated in the pancreas of their offspring. Conclusion NAC decreased morbidity of NOD mice by attenuating the immune response, presumably by eliminating oxidative stress, and might be beneficial in reducing morbidity rates of T1D in high-risk individuals.

Organophosphate pesticides and new-onset diabetes mellitus: From molecular mechanisms to a possible therapeutic perspective

“…Charron et al [ 85 ] also demonstrated that in high-fat diet-fed maternal mice, n-acetylcysteine supplementation in the maternal stage decreased diabetes mellitus development in offspring. A similar effect was also demonstrated in a type 1 diabetes mellitus animal model under insulin deficiency[ 86 ]. N-Acetylcysteine also lessened organophosphate-mediated toxicity in vivo .…”

Redox Balance in Type 2 Diabetes: Therapeutic Potential and the Challenge of Antioxidant-Based Therapy

“…Moreover, glucose reduces ROS levels in a dose-dependent manner [183], thus enabling proper secretion of insulin. We also found that low concentrations of 5 µM H 2 O 2 , which is within the physiological range, inhibited insulin secretion under low-glucose conditions, while insulin secretion, stimulated by high-glucose levels, was not impaired [184]. Cell death was observed only with higher doses of H 2 O 2 (100 µM), suggesting that the negative effect of H 2 O 2 on insulin secretion is mediated by redox regulation of the process, rather than an outcome of oxidative stress damage.…”

Clinical Relevance of lncRNA and Mitochondrial Targeted Antioxidants as Therapeutic Options in Regulating Oxidative Stress and Mitochondrial Function in Vascular Complications of Diabetes

“…It’s the only antioxidant drug to have clinical utility in improving a renal condition whose pathologic mechanism may involve oxidative stress. A pilot study demonstrated that NAC could not reduce serum biomarkers of oxidant stress in patients with diabetic proteinuria [ 134 ] even though preclinical studies have shown cardiovascular benefits or reduced progression of diabetes attributed to NAC-mediated inhibition of ROS production [ 137 , 138 , 139 ]. Intake of the fat-soluble vitamin E, known to be deficient in diabetes, was reported to be significantly associated with reduced risk of type 2 diabetes [ 140 ].…”