Pyrazinamide may possess cardioprotective properties

Sharabh Sinha, Qingyou Du, Sofija Jovanovic, Andriy Sukhodub, Aleksandar Jovanović (Lead / Corresponding author)

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Abstract

Pyrazinamide is an anti-tubercular agent, used as part of a three drug regime (any three of the following: rifampicin, isoniazid, pyrazinamide, streptomycin or ethambutol) for the initial phase of treatment. One of the effects pyrazinamide has on mammalian cells is to regulate NAD+/NADH levels. We have recently found that changes in NAD+/NADH are associated with regulation of expression levels of SUR2A, a cardioprotective protein serving as a regulatory subunit of cardiac ATP-sensitive K+ (KATP) channels. Here, we have tested whether pyrazinamide regulate expression of SUR2A/KATP channel subunits and resistance to metabolic stress in embryonic heart-derived H9c2 cells. We have found that 24h-long treatment with pyrazinamide (3 mcg/ml) increased mRNA levels of SUR2A, SUR2B and Kir6.1 without affecting mRNA levels of other KATP channel subunits. This treatment with pyrazinamide (3 mcg/ml) protected H9c2 cells against stress induced by 10 mM 2, 4-dinitrophenol (DNP). The survival rate of DNP treated cells was 45.6±2.3% (n = 5) if not treated with pyrazinamide and 90.8±2.3% (n = 5; P<0.001) if treated with pyrazinamide. We conclude that pyrazinamide increases resistance to metabolic stress in heart H9c2 cells probably by increasing SUR2A and SUR2B expression. Our results of this study indicate that pyrazinamide should be seriously considered as a drug of choice for patients that have tuberculosis and ischaemic heart disease.
Original languageEnglish
Pages (from-to)714-717
Number of pages4
JournalJournal of Antibiotics
Volume72
Early online date27 Jun 2019
DOIs
Publication statusPublished - 27 Jun 2019

Fingerprint

Pyrazinamide
NAD
KATP Channels
Physiological Stress
Dinitrophenols
2,4-Dinitrophenol
Ethambutol
Messenger RNA
Isoniazid
Streptomycin
Rifampin
Pharmaceutical Preparations
Myocardial Ischemia
Tuberculosis
Therapeutics
Survival Rate
Adenosine Triphosphate

Keywords

  • Tuberculosis
  • Ischemic Heart Disease
  • KATP channels
  • Carioprotection

Cite this

Sinha, S., Du, Q., Jovanovic, S., Sukhodub, A., & Jovanović, A. (2019). Pyrazinamide may possess cardioprotective properties. Journal of Antibiotics, 72, 714-717. https://doi.org/10.1038/s41429-019-0202-z
Sinha, Sharabh ; Du, Qingyou ; Jovanovic, Sofija ; Sukhodub, Andriy ; Jovanović, Aleksandar. / Pyrazinamide may possess cardioprotective properties. In: Journal of Antibiotics. 2019 ; Vol. 72. pp. 714-717.
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Sinha, S, Du, Q, Jovanovic, S, Sukhodub, A & Jovanović, A 2019, 'Pyrazinamide may possess cardioprotective properties', Journal of Antibiotics, vol. 72, pp. 714-717. https://doi.org/10.1038/s41429-019-0202-z

Pyrazinamide may possess cardioprotective properties. / Sinha, Sharabh; Du, Qingyou; Jovanovic, Sofija; Sukhodub, Andriy; Jovanović, Aleksandar (Lead / Corresponding author).

In: Journal of Antibiotics, Vol. 72, 27.06.2019, p. 714-717.

Research output: Contribution to journalArticle

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AU - Du, Qingyou

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AU - Sukhodub, Andriy

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