An in vitro study on the combination effect of Metformin and N-Acetyl Cysteine against hyperglycaemia-induced cardiac damage

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dc.contributor.authorJohnson, Rabiaen_ZA
dc.contributor.authorSangweni, Nonhlakanipho F.en_ZA
dc.contributor.authorMabhida, Sihle E.en_ZA
dc.contributor.authorDludla, Phiwayinkosi V.en_ZA
dc.contributor.authorMabasa, Lawrenceen_ZA
dc.contributor.authorRiedel, Sylviaen_ZA
dc.contributor.authorChapman, Charnaen_ZA
dc.contributor.authorMosa, Rebamang A.en_ZA
dc.contributor.authorKappo, Abidemi P.en_ZA
dc.contributor.authorLouw, Johanen_ZA
dc.contributor.authorMuller, Christo J. F.en_ZA
dc.date.accessioned2021-10-19T07:51:41Z
dc.date.available2021-10-19T07:51:41Z
dc.date.issued2019-11-21
dc.descriptionCITATION: Johnson R, et al. 2019. An In Vitro Study on the Combination Effect of Metformin and N-Acetyl Cysteine against Hyperglycaemia-Induced Cardiac Damage. Nutrients, 11(12). doi:10.3390/nu11122850
dc.descriptionThe original publication is available at https://www.mdpi.com/journal/nutrients
dc.description.abstractENGLISH ABSTRACT: Chronic hyperglycaemia is a major risk factor for diabetes-induced cardiovascular dysfunction. In a hyperglycaemic state, excess production of reactive oxygen species (ROS), coupled with decreased levels of glutathione, contribute to increased lipid peroxidation and subsequent myocardial apoptosis. N-acetylcysteine (NAC) is a thiol-containing antioxidant known to protect against hyperglycaemic-induced oxidative stress by promoting the production of glutathione. While the role of NAC against oxidative stress-related cardiac dysfunction has been documented, to date data is lacking on its beneficial effect when used with glucose lowering therapies, such as metformin (MET). Thus, the aim of the study was to better understand the cardioprotective effect of NAC plus MET against hyperglycaemia-induced cardiac damage in an H9c2 cardiomyoblast model. H9c2 cardiomyoblasts were exposed to chronic high glucose concentrations for 24 h. Thereafter, cells were treated with MET, NAC or a combination of MET and NAC for an additional 24 h. The combination treatment mitigated high glucose-induced oxidative stress by improving metabolic activity i.e. ATP activity, glucose uptake (GU) and reducing lipid accumulation. The combination treatment was as effective as MET in diminishing oxidative stress, lipid peroxidation and apoptosis. We observed that the combination treatment prevented hyperglycaemic-induced cardiac damage by increasing GLUT4 expression and mitigating lipid accumulation via phosphorylation of both AMPK and AKT, while decreasing nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), as well as protein kinase C (PKC), a known activator of insulin receptor substrate-1 (IRS-1), via phosphorylation at Ser307. On this basis, the current results support the notion that the combination of NAC and MET can shield the diabetic heart against impaired glucose utilization and therefore its long-term protective effect warrants further investigation.en_ZA
dc.description.urihttps://www.mdpi.com/2072-6643/11/12/2850
dc.description.versionPublisher’s version
dc.format.extent19 pagesen_ZA
dc.identifier.citationJohnson R, et al. 2019. An In Vitro Study on the Combination Effect of Metformin and N-Acetyl Cysteine against Hyperglycaemia-Induced Cardiac Damage. Nutrients, 11(12). doi:10.3390/nu11122850
dc.identifier.issn2072-6643 (online)
dc.identifier.otherdoi:10.3390/nu11122850
dc.identifier.urihttp://hdl.handle.net/10019.1/123247
dc.language.isoen_ZAen_ZA
dc.publisherMDPIen_ZA
dc.rights.holderAuthors retain rightsen_ZA
dc.subjectOxidative stressen_ZA
dc.subjectDiabetesen_ZA
dc.subjectApoptosisen_ZA
dc.subjectN-acetyl cysteineen_ZA
dc.subjectMetforminen_ZA
dc.subjectCardiovascularen_ZA
dc.titleAn in vitro study on the combination effect of Metformin and N-Acetyl Cysteine against hyperglycaemia-induced cardiac damageen_ZA
dc.typeArticleen_ZA
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