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Medical Gas Research

, 2:28

CO in biology and medicine

Abstract

Carbon monoxide-releasing molecules CO-RMs are a class of organometallo compounds capable of delivering controlled quantities of CO gas to cells and tissues thus exerting a broad spectrum of pharmacological effects. CO-RMs containing transition metal carbonyls were initially implemented to mimic the function of heme oxygenase-1 HMOX1, a stress inducible defensive protein that degrades heme to CO and biliverdin leading to anti-oxidant and anti-inflammatory actions. Ten years after their discovery, the research on the chemistry and biological activities of CO-RMs has greatly intensified indicating that their potential use as CO delivering agents for the treatment of several pathological conditions is feasible. Although CO-RMs are a class of compounds that structurally diverge from traditional organic-like pharmaceuticals, their behaviour in the biological environments is progressively being elucidated revealing interesting features of metal-carbonyl chemistry towards cellular targets. Specifically, the presence of carbonyl groups bound to transition metals such as ruthenium, iron or manganese appears to make CO-RMs unique in their ability to transfer CO intracellularly and amplify the mechanisms of signal transduction mediated by CO. In addition to their well-established vasodilatory activities and protective effects against organ ischemic damage, CO-RMs are emerging for their striking anti-inflammatory properties which may be the result of the multiple activities of metal carbonyls in the control of redox signaling, oxidative stress and cellular respiration. Here, we review evidence on the pharmacological effects of CO-RMs in models of acute and chronic inflammation elaborating on some emerging concepts that may help to explain the chemical reactivity and mechanisms of action of this distinctive class of compounds in biological systems.

KeywordsInflammation Carbon monoxide-releasing molecules CO-RMs Oxidative stress Inflammatory mediators Bactericidal activities AbbreviationsCLPCecal ligation and puncture

COCarbon monoxide

CO-RMsCarbon monoxide-releasing molecules

COCarbon monoxide

CORM-2RuCO3Cl22 also known as tricarbonyldichlororutheniumII dimer

CORM-3RuCO3Clglycinate also known as tricarbonylchloroglycinatorutheniumII

CORM-371Me4NMnCO4thioacetate2

CORM-A1NaH3BCOOH, also known as sodium boranocarbonates

COX-2Cyclooxygenase-2

HbHemoglobin

HMOX1Heme oxygenase-1

ICAM-1Intercellular adhesion molecule 1

ILInterleukin

IL-1βInterleukin 1 beta

iNOSInducible nitric oxide synthase or NOSIII

LPSLypopolysaccharide

MAPKsMitogen activated protein kinases

MbMyoglobin

MbCOCarbon monoxy myoglobin

MMPMatrix metallo proteinase

MPOMyeloperoxidase

NONitric oxide

NfkβNuclear factor kappa beta

O2Superoxide anion

PGE2Prostaglandin E2

PMNsPolymorphonuclear neutrophils

ROSReactive oxygen species

TNF-αTumor necrosis factor alpha.

Electronic supplementary materialThe online version of this article doi:10.1186-2045-9912-2-28 contains supplementary material, which is available to authorized users.

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Autor: Roberto Motterlini - Benjamin Haas - Roberta Foresti

Fuente: https://link.springer.com/







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