Cardioprotective potential of N-acetyl cysteine against hyperglycaemia-induced oxidative damage: a protocol for a systematic review

Abstract

BackgroundHyperglycaemia-induced oxidative damage is a well-established factor implicated in the development of diabetic cardiomyopathy (DCM) in diabetic individuals. Some of the well-known characteristics of DCM include increased myocardial left ventricular wall thickness and remodelling that result in reduced cardiac efficiency. To prevent this, an increasing number of pharmacological compounds such as N-acetyl cysteine (NAC) are explored for their antioxidant properties. A few studies have shown that NAC can ameliorate hyperglycaemia-induced oxidative damage within the heart. Hence, the objective of this review is to synthesise the available evidence pertaining to the cardioprotective role of NAC against hyperglycaemia-induced oxidative damage and thus prevent DCM.MethodsThis systematic review protocol will be reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement. We will perform a comprehensive search on major databases such as EMBASE, Cochrane Library, PubMed and Google scholar for original research articles published from January 1960 to March 2017. We will only report on literature that is available in English. Two authors will independently screen for eligible studies using pre-defined criteria, and data extraction will be done in duplicate. All discrepancies will be resolved by consensus or consultation of a third reviewer. The quality of studies will be checked using Cochrane Risk of Bias Assessment Tool and The Joanna Briggs Institute (JBI) Critical Appraisal tools for non-randomised experimental studies. Heterogeneity across studies will be assessed using the Cochrane Q statistic and the inconsistency index (I 2). We will use the random effects model to calculate a pooled estimate.DiscussionAlthough several studies have shown that NAC can ameliorate hyperglycaemia-induced oxidative damage within the heart, this systematic review will be the first pre-registered synthesis of data to identify the cardioprotective potential of NAC against hyperglycaemia-induced oxidative damage. This result will help guide future research evaluating the cardioprotective role of NAC against DCM and better identify possible mechanisms of action for NAC to prevent oxidative damage with a diabetic heart.Systemic review registrationPROSPERO CRD42017055851.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-017-0493-8) contains supplementary material, which is available to authorized users.

MicroRNA and ROS Crosstalk in Cardiac and Pulmonary Diseases

“…Oxidative stress is well known to play a negative role in the development of chronic vascular complications, especially in patients with diabetes mellitus (DM) [32]. In diabetic cardiomyopathy (DCM), myocardial apoptosis is directly related to the generation of ROS in the heart, which is considered to be critical in the development and progression of DCM [97][98][99].…”

Therapeutic Efficacy of Antioxidants in Ameliorating Obesity Phenotype and Associated Comorbidities

“…The current cumulative line of evidence strongly suggests that NAC may have a role in being utilized as a cardioprotective agent by reducing hyperglycemia induced oxidative damage to cardiac myocytes and cardiac remodeling ( Chen et al., 1985 ; Dludla et al., 2017 ). This reduction in oxidative stress attenuates a progressive loss in cardiac efficiency and cardiac fibrosis that would have progressed to more severe clinical outcomes prior to intervention ( Seddon et al., 2007 ; Talasaz et al., 2013 ).…”

“…This reduction in oxidative stress attenuates a progressive loss in cardiac efficiency and cardiac fibrosis that would have progressed to more severe clinical outcomes prior to intervention ( Seddon et al., 2007 ; Talasaz et al., 2013 ). Data from multiple studies indicated that NAC elevated levels of SOD and glutathione in cardiac myocytes, while reducing levels of TGF-β, lipid hydroperoxides and various biomarkers for oxidative stress ( Haleagrahara et al., 2011 ; Talasaz et al., 2013 ; Dludla et al., 2017 ). Obesity and T2DM both exhibit a characteristic feature of hypercoagulable states through chronic inflammation associated with obesity and dysregulation of platelet aggregation ( Anderson and Weitz, 2010 ; Blokhin and Lentz, 2013 ; Widjaja et al., 2019 ).…”

Study of superoxide- and NO-dependent protective mechanisms of N-acetylcysteine and losartan in ratʼs aorta and liver under streptozoticin-induced type 1 diabetes mellitus

“…NAC -is well-known synthetic mucolytic agent with AO properties due to its SH-group and ability to synthesize reduced glutathione. Lately, the possibility of NAC usage in correction of cardiovascular complications in case of diabetes mellitus has been actively discussed [9]. In experimental works, NAC increased activity of aldehyde dehydrogenase 2 -a key cardioprotective enzyme susceptible to oxidative inactivation in diabetic heart [8].…”

“…Lately, the effectiveness of synthetic antioxidant N-acetylcysteine (NAC) for correction of cardiovascular diseases in experiments in vivo has been actively discussed [7,8]. The recent systemic review has also pointed out that NAC has cardioprotective potential in case of hyperglycemia-induced OS [9].…”