An In Vitro Study on the Combination Effect of Metformin and N-Acetyl Cysteine against Hyperglycaemia-Induced Cardiac Damage.
N-acetyl cysteine
apoptosis
cardiovascular
diabetes
metformin
oxidative stress
Journal
Nutrients
ISSN: 2072-6643
Titre abrégé: Nutrients
Pays: Switzerland
ID NLM: 101521595
Informations de publication
Date de publication:
21 Nov 2019
21 Nov 2019
Historique:
received:
23
10
2019
revised:
08
11
2019
accepted:
11
11
2019
entrez:
27
11
2019
pubmed:
27
11
2019
medline:
30
5
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31766382
pii: nu11122850
doi: 10.3390/nu11122850
pmc: PMC6950330
pii:
doi:
Substances chimiques
Cardiotonic Agents
0
Metformin
9100L32L2N
Glucose
IY9XDZ35W2
Acetylcysteine
WYQ7N0BPYC
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Rabia Johnson
ID : 10726
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