Pyrazinamide may possess cardioprotective properties

Abstract

Pyrazinamide is an anti-tubercular agent, used as a 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 24-h-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 with tuberculosis and ischaemic heart disease.

Comparison of the Efficacy of Longer versus Shorter Pulsed High Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome with Bartonellosis and Associated Coinfections

“…Higher methylene blue dosage as well as extending the length of time on high-dose dapsone (200 mg PO BID) from 4 days to 6–7 days improved response and remission rates, especially in those co-infected with Bartonella . Pyrazinamide may also have been helpful in inducing remission rates for Bartonella ; however, larger controlled studies will be necessary to determine its beneficial effect [ 325 , 326 ]. Of 23 patients who completed a full 8-week course of DDDCT prior to one or several courses of HDDCT, 7/23 (30.5%) had a full resolution of their Lyme and tick-borne symptoms for 3 months or longer, even if there was prior evidence of co-infections, including Babesia and/or Bartonella.…”

Caudatin Inhibits the Proliferation, Invasion, and Glycolysis of Osteosarcoma Cells via the Wnt/β- Catenin Pathway

“…Glucose and lactic acid are the raw materials and metabolites of aerobic glycolysis, which is the main metabolic support for cancer development [20,21]. ATP is the major energy carrier supporting diferent cellular processes [23]. In addition, high levels of ATP and a low ratio of Evidence-Based Complementary and Alternative Medicine NAD + /NADH are the characteristics of the energy metabolism of tumor cells [24][25][26].…”

SUR2A: How to exploit this protein to treat ischaemic heart disease?

“…S obzirim da su kontraindikacije i interakcije lekova sa nikotinamidom retke, gotovo svaki bolesnik koji boluje od ishemijske bolesti srca bi mogao koristiti nikotinamid. Ove godine smo pronašli da još jedan lek koji moduliše NADH/NAD + , anti-tuberkulotik pirazinamid, ima, bar na ćelijskom nivou, efekat na SUR2A koji je sličan efektu nikotinamida [30]. Za razliku od nikotinamida, pirazinamid izaziva značajna neželjena dejstva, kao što su hepatitis, anoreksija, nefritis i mnoge druge [31], što čini ovaj lek manje pogodnim za terapijsku upotrebu od nikotinamida.…”