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L-NAME Improves Doxycycline and ML-7 Cardioprotection From Oxidative Stress

L-NAME Improves Doxycycline and ML-7 Cardioprotection From Oxidative Stress

Iwona Bil-Lula, Anna Krzywonos-Zawadzka, Jolanta Sawicka, Dariusz Bialy, Magdalena Wawrzynska, Mieczyslaw Wozniak, Grzegorz Sawicki

Front Biosci (Landmark Ed). 2018 Jan 1;23:298-309.

PMID: 28930548

Abstract:

Matrix metalloproteinase-2 (MMP-2) mediated degradation of myosin light chain 1 (MLC1) and troponin I (TnI) contributes to myocardial ischemia/reperfusion (I/R) injury. Modifications of MLC1 triggered by oxidative stress are mediated by myosin light chain kinase (MLCK), nitric oxide synthase (NOS), and MMP-2. Previous studies have shown that inhibiting both MLCK and MMP-2 protects against I/R injury. Here, we hypothesized that the addition of NOS inhibitor (L-NAME) at subprotective concentration to the mixture of subprotective concentrations of ML-7 and doxycycline (Doxy), will increase a synergistic cardioprotection of Doxy and ML-7 during I/R. Isolated rat hearts were subjected to global ischemia without or with administration of the mixture of inhibitors. Markers of I/R injury were measured in hearts and coronary effluents. Addition of L-NAME to the mixture of Doxy and ML-7 led to full recovery of heart contractility in comparison to combination of Doxy and ML-7. Improved heart contractility was associated with reduced degradation of TnI and MLC1. The combined administration of NOS, MMP-2 and MLCK inhibitors provides a novel strategy to protect heart from I/R injury.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP110448334-A	ML-7		110448-33-4	Price

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