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Front Biosci (Landmark Ed). 2020 Jan 1;25:722-735.

A drug cocktail for protecting against ischemia-reperfusion injury.

Author information

1
Department of Medical Laboratory Diagnostics, Division of Clinical Chemistry, Wroclaw Medical University, ul. Borowska 211A, 50-556 Wroclaw, Poland.
2
Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
3
Department of Medical Laboratory Diagnostics, Division of Clinical Chemistry, Wroclaw Medical University, Ul. Borowska 211A, 50-556 Wroclaw, Poland, iwona.bil-lula@umed.wroc.pl.

Abstract

Ischemia followed by reperfusion (I/R) of cardiomyocytes causes release of a large amount of inducible nitric oxide (NO) synthase (iNOS) followed by an increase of asymmetric dimethylarginine (ADMA). ADMA disrupts NO signaling by switching of the NOS activity from NO to the production of reactive oxygen species (ROS). Previously, we have shown that pretreatment of the hearts by co-administration of sub-threshold concentrations of doxycycline, a matrix metalloproteinase (MMPs) inhibitor, ML-7 an inhibitor of myosin light-chain kinase (MLCK) and L-NAME a non-selective NOS inhibitor protects the heart against I/R injury. In this study, we replaced the L-NAME with 1400W (selective inhibitor of iNOS) in the drug cocktail that was Langendorff-perfused into the hearts of Wistar rats before (prevention) or after (treatment) the induction of I/R. This pre-treatment resulted in full protection of contractility, decreased production of iNOS and ADMA and normalized the bioavailability of NO in the I/R hearts. Thus, the formulated drug cocktail protects the heart from I/R injury.

PMID:
31585914

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