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Pyrazinamide may possess cardioprotective properties
Sharabh Sinha1, Qingyou Du1, Sofija Jovanović1
1Division of Molecular and Clinical Medicine, Medical School, University of Dundee, Nethergate, Dundee, DD1 4HN, UK.
The Journal of Antibiotics
|June 28, 2019
Summary
Pyrazinamide, an anti-tuberculosis drug, enhances heart cell survival against metabolic stress by increasing SUR2A and SUR2B expression. This suggests pyrazinamide may benefit patients with both tuberculosis and ischemic heart disease.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Pyrazinamide is a first-line anti-tuberculosis drug.
- Pyrazinamide influences cellular NAD+/NADH levels.
- NAD+/NADH levels are linked to SUR2A expression, a key component of cardiac ATP-sensitive potassium (KATP) channels.
Purpose of the Study:
- To investigate if pyrazinamide modulates SUR2A/KATP channel subunit expression.
- To determine if pyrazinamide enhances resistance to metabolic stress in cardiac cells.
Main Methods:
- Treatment of embryonic heart-derived H9c2 cells with pyrazinamide (3 mcg/ml) for 24 hours.
- Assessment of mRNA levels for KATP channel subunits (SUR2A, SUR2B, Kir6.1, etc.).
- Evaluation of H9c2 cell survival under metabolic stress induced by 2,4-dinitrophenol (DNP).
Main Results:
- Pyrazinamide treatment significantly increased mRNA levels of SUR2A, SUR2B, and Kir6.1.
- Pyrazinamide pre-treatment markedly improved H9c2 cell survival under DNP-induced metabolic stress (90.8% vs 45.6%).
Conclusions:
- Pyrazinamide increases the expression of SUR2A and SUR2B.
- Pyrazinamide confers significant protection to cardiac H9c2 cells against metabolic stress.
- Pyrazinamide is a potential therapeutic agent for patients with co-existing tuberculosis and ischemic heart disease.
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