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Published in: Systematic Reviews 1/2017

Open Access 01-12-2017 | Protocol

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

Authors: Phiwayinkosi V. Dludla, Bongani B. Nkambule, Stephanie C. Dias, Rabia Johnson

Published in: Systematic Reviews | Issue 1/2017

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Abstract

Background

Hyperglycaemia-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.

Methods

This 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.

Discussion

Although 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 registration

PROSPERO CRD42017055851.
Appendix
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Literature
3.
go back to reference Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339(4):229–34.CrossRefPubMed Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339(4):229–34.CrossRefPubMed
4.
go back to reference Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972;30(6):595–602.CrossRefPubMed Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972;30(6):595–602.CrossRefPubMed
5.
go back to reference Tarquini R, Lazzeri C, Pala L, Rotella CM, Gensini GF. The diabetic cardiomyopathy. Acta Diabetol. 2011;48(3):173–81.CrossRefPubMed Tarquini R, Lazzeri C, Pala L, Rotella CM, Gensini GF. The diabetic cardiomyopathy. Acta Diabetol. 2011;48(3):173–81.CrossRefPubMed
7.
go back to reference Pappachan JM, Varughese GI, Sriraman R, Arunagirinathan G. Diabetic cardiomyopathy: pathophysiology, diagnostic evaluation and management. World J Diabetes. 2013;4(5):177–89.PubMedPubMedCentral Pappachan JM, Varughese GI, Sriraman R, Arunagirinathan G. Diabetic cardiomyopathy: pathophysiology, diagnostic evaluation and management. World J Diabetes. 2013;4(5):177–89.PubMedPubMedCentral
8.
go back to reference Jonassen AK, Sack MN, Mjøs OD, Yellon DM. Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling. Circ Res. 2001;89(12):1191–8.CrossRefPubMed Jonassen AK, Sack MN, Mjøs OD, Yellon DM. Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling. Circ Res. 2001;89(12):1191–8.CrossRefPubMed
9.
go back to reference Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 2005;28(10):2345–51.CrossRefPubMed Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care. 2005;28(10):2345–51.CrossRefPubMed
10.
go back to reference Yin M, van der Horst ICC, van Melle JP, Qian C, van Gilst WH, Silljé HHW, et al. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol. 2011;301(2):H459–68.CrossRefPubMed Yin M, van der Horst ICC, van Melle JP, Qian C, van Gilst WH, Silljé HHW, et al. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol. 2011;301(2):H459–68.CrossRefPubMed
11.
go back to reference Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(8):140–9.CrossRefPubMed Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(8):140–9.CrossRefPubMed
13.
go back to reference Chaumais MC, Ranchoux B, Montani D, Dorfmüller P, Tu L, Lecerf F, et al. N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats. Respir Res. 2014;15:65.CrossRefPubMedPubMedCentral Chaumais MC, Ranchoux B, Montani D, Dorfmüller P, Tu L, Lecerf F, et al. N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats. Respir Res. 2014;15:65.CrossRefPubMedPubMedCentral
14.
go back to reference Farshid AA, Tamaddonfard E, Simaee N, Mansouri S, Najafi S, Asri-Rezaee S, et al. Effects of histidine and N-acetylcysteine on doxorubicin-induced cardiomyopathy in rats. Cardiovasc Toxicol. 2014;14(2):153–61.CrossRefPubMed Farshid AA, Tamaddonfard E, Simaee N, Mansouri S, Najafi S, Asri-Rezaee S, et al. Effects of histidine and N-acetylcysteine on doxorubicin-induced cardiomyopathy in rats. Cardiovasc Toxicol. 2014;14(2):153–61.CrossRefPubMed
15.
go back to reference Fischell TA. Contrast loaded with N-acetylcysteine for coronary imaging during percutaneous coronary intervention: a new concept for renal and myocardial protection during percutaneous coronary intervention. JACC Cardiovasc Interv. 2009;2(3):222–3.CrossRefPubMed Fischell TA. Contrast loaded with N-acetylcysteine for coronary imaging during percutaneous coronary intervention: a new concept for renal and myocardial protection during percutaneous coronary intervention. JACC Cardiovasc Interv. 2009;2(3):222–3.CrossRefPubMed
16.
go back to reference Meyer M, LeWinter MM, Bell SP, Chen Z, Selby DE, Singla DK, et al. N-acetylcysteine enhanced contrast provides cardiorenal protection. JACC Cardiovasc Interv. 2009;2(3):215–21.CrossRefPubMedPubMedCentral Meyer M, LeWinter MM, Bell SP, Chen Z, Selby DE, Singla DK, et al. N-acetylcysteine enhanced contrast provides cardiorenal protection. JACC Cardiovasc Interv. 2009;2(3):215–21.CrossRefPubMedPubMedCentral
17.
go back to reference Wu XY, Luo AY, Zhou YR, Ren JH. N-acetylcysteine reduces oxidative stress, nuclear factor-κB activity and cardiomyocyte apoptosis in heart failure. Mol Med Rep. 2014;10(2):615–24.PubMedPubMedCentral Wu XY, Luo AY, Zhou YR, Ren JH. N-acetylcysteine reduces oxidative stress, nuclear factor-κB activity and cardiomyocyte apoptosis in heart failure. Mol Med Rep. 2014;10(2):615–24.PubMedPubMedCentral
18.
go back to reference Dludla PV, Muller CJ, Louw J, Joubert E, Salie R, Opoku AR, et al. The cardioprotective effect of an aqueous extract of fermented rooibos (Aspalathus linearis) on cultured cardiomyocytes derived from diabetic rats. Phytomedicine. 2014;21(5):595–601.CrossRefPubMed Dludla PV, Muller CJ, Louw J, Joubert E, Salie R, Opoku AR, et al. The cardioprotective effect of an aqueous extract of fermented rooibos (Aspalathus linearis) on cultured cardiomyocytes derived from diabetic rats. Phytomedicine. 2014;21(5):595–601.CrossRefPubMed
19.
go back to reference Haleagrahara N, Julian V, Chakravarthi S. N-acetylcysteine offers cardioprotection by decreasing cardiac lipid hydroperoxides and 8-isoprostane level in isoproterenol-induced cardiotoxicity in rats. Cardiovasc Toxicol. 2011;11(4):373–81.CrossRefPubMed Haleagrahara N, Julian V, Chakravarthi S. N-acetylcysteine offers cardioprotection by decreasing cardiac lipid hydroperoxides and 8-isoprostane level in isoproterenol-induced cardiotoxicity in rats. Cardiovasc Toxicol. 2011;11(4):373–81.CrossRefPubMed
20.
go back to reference Burgunder JM, Varriale A, Lauterburg BH. Effect of N-acetylcysteine on plasma cysteine and glutathione following paracetamol administration. Eur J Clin Pharmacol. 1989;36(2):127–31.CrossRefPubMed Burgunder JM, Varriale A, Lauterburg BH. Effect of N-acetylcysteine on plasma cysteine and glutathione following paracetamol administration. Eur J Clin Pharmacol. 1989;36(2):127–31.CrossRefPubMed
21.
go back to reference Kerksick C, Willoughby D. The antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stress. J Int Soc Sports Nutr. 2005;2(2):38–44.CrossRefPubMedPubMedCentral Kerksick C, Willoughby D. The antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stress. J Int Soc Sports Nutr. 2005;2(2):38–44.CrossRefPubMedPubMedCentral
22.
go back to reference Giam B, Chu PY, Kuruppu S, Smith AI, Horlock D, Kiriazis H, et al. N-acetylcysteine attenuates the development of cardiac fibrosis and remodeling in a mouse model of heart failure. Physiol Rep. 2016;4(7):e12757.CrossRefPubMedPubMedCentral Giam B, Chu PY, Kuruppu S, Smith AI, Horlock D, Kiriazis H, et al. N-acetylcysteine attenuates the development of cardiac fibrosis and remodeling in a mouse model of heart failure. Physiol Rep. 2016;4(7):e12757.CrossRefPubMedPubMedCentral
23.
go back to reference Rajapakse N, Giam B, Chu PY, Kiriazis H, Du XN, Kaye DM. N-acetylcysteine reverses established cardiac and renal fibrosis in a mouse model of heart failure. FASEB J. 2016;30(1):Suppl. 735. Rajapakse N, Giam B, Chu PY, Kiriazis H, Du XN, Kaye DM. N-acetylcysteine reverses established cardiac and renal fibrosis in a mouse model of heart failure. FASEB J. 2016;30(1):Suppl. 735.
24.
go back to reference Liu C, Lu XZ, Shen MZ, Xing CY, Ma J, Duan YY, Yuan LJ. N-acetyl cysteine improves the diabetic cardiac function: possible role of fibrosis inhibition. BMC Cardiovasc Disord. 2015;15:84.CrossRefPubMedPubMedCentral Liu C, Lu XZ, Shen MZ, Xing CY, Ma J, Duan YY, Yuan LJ. N-acetyl cysteine improves the diabetic cardiac function: possible role of fibrosis inhibition. BMC Cardiovasc Disord. 2015;15:84.CrossRefPubMedPubMedCentral
25.
go back to reference Suddarth SB. Acetylcysteine, a new and effective mucolytic agent. Bull Geisinger. 1963;15:65–9.PubMed Suddarth SB. Acetylcysteine, a new and effective mucolytic agent. Bull Geisinger. 1963;15:65–9.PubMed
26.
go back to reference Babineau J. Product review: covidence (systematic review software). J Can Health Libr Assoc. 2014;35(2):68–71.CrossRef Babineau J. Product review: covidence (systematic review software). J Can Health Libr Assoc. 2014;35(2):68–71.CrossRef
27.
go back to reference Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.CrossRefPubMedPubMedCentral Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.CrossRefPubMedPubMedCentral
28.
go back to reference Foster J, Burry LD, Thabane L, Choong K, Menon K, Duffett M, Cheung A, Guenette M, Chimunda T, Rose L. Melatonin and melatonin agonists to prevent and treat delirium in critical illness: a systematic review protocol. Syst Rev. 2016;5(1):199.CrossRefPubMedPubMedCentral Foster J, Burry LD, Thabane L, Choong K, Menon K, Duffett M, Cheung A, Guenette M, Chimunda T, Rose L. Melatonin and melatonin agonists to prevent and treat delirium in critical illness: a systematic review protocol. Syst Rev. 2016;5(1):199.CrossRefPubMedPubMedCentral
29.
go back to reference The Joanna Briggs Institute. Joanna Briggs Institute reviewers’ manual: 2016 edition. Australia: The Joanna Briggs Institute; 2016. The Joanna Briggs Institute. Joanna Briggs Institute reviewers’ manual: 2016 edition. Australia: The Joanna Briggs Institute; 2016.
30.
go back to reference Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–6.CrossRefPubMedPubMedCentral Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–6.CrossRefPubMedPubMedCentral
31.
go back to reference Higgins JPT, Green S (eds). Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011. Available from: http://handbook.cochrane.org/. Accessed 07 Mar 2017. Higgins JPT, Green S (eds). Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011. Available from: http://​handbook.​cochrane.​org/​. Accessed 07 Mar 2017.
33.
go back to reference Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.CrossRefPubMed Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.CrossRefPubMed
34.
go back to reference The Nordic Cochrane Centre, The Cochrane Collaboration. Review manager (RevMan). 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2014. The Nordic Cochrane Centre, The Cochrane Collaboration. Review manager (RevMan). 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2014.
35.
go back to reference Bai Y, Cui W, Xin Y, Miao X, Barati MT, Zhang C. Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation. J Mol Cell Cardiol. 2013;57:82–95.CrossRefPubMed Bai Y, Cui W, Xin Y, Miao X, Barati MT, Zhang C. Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation. J Mol Cell Cardiol. 2013;57:82–95.CrossRefPubMed
36.
go back to reference Xu J, Li H, Irwin MG, Xia ZY, Mao X, Lei S, et al. Propofol ameliorates hyperglycemia-induced cardiac hypertrophy and dysfunction via heme oxygenase-1/signal transducer and activator of transcription 3 signaling pathway in rats. Crit Care Med. 2014;42(8):e583–94.CrossRefPubMed Xu J, Li H, Irwin MG, Xia ZY, Mao X, Lei S, et al. Propofol ameliorates hyperglycemia-induced cardiac hypertrophy and dysfunction via heme oxygenase-1/signal transducer and activator of transcription 3 signaling pathway in rats. Crit Care Med. 2014;42(8):e583–94.CrossRefPubMed
37.
go back to reference Dludla PV, Muller CJF, Joubert E, Louw J, Essop MF, Gabuza KB, et al. Aspalathin protects the heart against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression. Molecules. 2017;22(1). doi:10.3390/molecules22010129. Dludla PV, Muller CJF, Joubert E, Louw J, Essop MF, Gabuza KB, et al. Aspalathin protects the heart against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression. Molecules. 2017;22(1). doi:10.​3390/​molecules2201012​9.
38.
go back to reference Dludla PV, Muller CJ, Joubert E, Louw J, Gabuza KB, Huisamen B, et al. Phenylpyruvic acid-2-O-β-D-glucoside attenuates high glucose-induced apoptosis in H9c2 cardiomyocytes. Planta Med. 2016;82(17):1468–74.CrossRefPubMed Dludla PV, Muller CJ, Joubert E, Louw J, Gabuza KB, Huisamen B, et al. Phenylpyruvic acid-2-O-β-D-glucoside attenuates high glucose-induced apoptosis in H9c2 cardiomyocytes. Planta Med. 2016;82(17):1468–74.CrossRefPubMed
39.
go back to reference Johnson R, Dludla P, Joubert E, February F, Mazibuko S, Ghoor S, et al. Aspalathin, a dihydrochalcone C-glucoside, protects H9c2 cardiomyocytes against high glucose induced shifts in substrate preference and apoptosis. Mol Nutr Food Res. 2016;60(4):922–34.CrossRefPubMed Johnson R, Dludla P, Joubert E, February F, Mazibuko S, Ghoor S, et al. Aspalathin, a dihydrochalcone C-glucoside, protects H9c2 cardiomyocytes against high glucose induced shifts in substrate preference and apoptosis. Mol Nutr Food Res. 2016;60(4):922–34.CrossRefPubMed
40.
go back to reference Johnson R, Dludla PV, Muller CJ, Huisamen B, Essop MF, Louw J. The transcription profile unveils the cardioprotective effect of aspalathin against lipid toxicity in an in vitro H9c2 model. Molecules. 2017;22(2). doi:10.3390/molecules22020219. Johnson R, Dludla PV, Muller CJ, Huisamen B, Essop MF, Louw J. The transcription profile unveils the cardioprotective effect of aspalathin against lipid toxicity in an in vitro H9c2 model. Molecules. 2017;22(2). doi:10.​3390/​molecules2202021​9.
Metadata
Title
Cardioprotective potential of N-acetyl cysteine against hyperglycaemia-induced oxidative damage: a protocol for a systematic review
Authors
Phiwayinkosi V. Dludla
Bongani B. Nkambule
Stephanie C. Dias
Rabia Johnson
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Systematic Reviews / Issue 1/2017
Electronic ISSN: 2046-4053
DOI
https://doi.org/10.1186/s13643-017-0493-8

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