Lipophilic siderophores of Mycobacterium tuberculosis prevent cardiac reperfusion injury

Lawrence D Horwitz; Nancy A Sherman; Yinong Kong; Adrian W Pike; Jovana Gobin; Paul V Fennessey; Marcus A Horwitz

doi:10.1073/pnas.95.9.5263

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Lipophilic siderophores of Mycobacterium tuberculosis prevent cardiac reperfusion injury

Journal article

Open access

Lipophilic siderophores of Mycobacterium tuberculosis prevent cardiac reperfusion injury

Lawrence D Horwitz, Nancy A Sherman, Yinong Kong, Adrian W Pike, Jovana Gobin, Paul V Fennessey and Marcus A Horwitz

Proceedings of the National Academy of Sciences of the United States of America, Vol.95(9), pp.5263-5268

04/28/1998

DOI: 10.1073/pnas.95.9.5263

PMCID: PMC20249

PMID: 9560264

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Abstract

Reperfusion injury, which occurs upon the reintroduction of blood flow to an ischemic organ, is responsible for considerable damage in heart attacks and strokes. However, no treatment for reperfusion injury is currently available. A major cause of reperfusion injury is the iron-mediated generation of hydroxyl radical (.OH). In this study we have explored the capacity of novel iron chelators called "exochelins" to prevent reperfusion injury. Exochelins, siderophores of Mycobacterium tuberculosis, are unique iron chelators because they are lipid soluble, and hence able to enter cells rapidly. In the iron-free state, exochelins prevented .OH formation. Desferri-exochelins prevented oxidative injury to cultured cardiac myocytes, and did so more rapidly and effectively than the nonlipid soluble iron chelator deferoxamine. The capacity of various desferri-exochelins to protect myocytes from oxidative injury varied directly with their solubility in lipid. Infused into isolated rabbit hearts during reperfusion after a period of ischemia, desferri-exochelins dramatically improved systolic and diastolic left ventricular function, preserved coronary flow, reduced release of the cardiac enzyme lactic dehydrogenase, and reduced myocardial concentrations of .OH metabolites. Thus, highly diffusible desferri-exochelins block injury caused by .OH production and have potential for the treatment of reperfusion injury.

Peptides

Tuberculosis

2.1 Biological and endogenous factors

5.1 Pharmaceuticals

Aetiology

Animals

Cardiovascular

Cells

Cultured

Cyclic

Development of treatments and therapeutic interventions

Good Health and Well Being

Heart Disease

Heart Disease - Coronary Heart Disease

Hydrogen Peroxide

Male

Mycobacterium tuberculosis

Myocardial Reperfusion Injury

Prevention

Rabbits

Rare Diseases

Rats

Reactive Oxygen Species

Siderophores

Solubility

Superoxides

Details

Title: Subtitle: Lipophilic siderophores of Mycobacterium tuberculosis prevent cardiac reperfusion injury
Creators: Lawrence D Horwitz
Nancy A Sherman
Yinong Kong
Adrian W Pike
Jovana Gobin
Paul V Fennessey
Marcus A Horwitz
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences of the United States of America, Vol.95(9), pp.5263-5268
DOI: 10.1073/pnas.95.9.5263
PMID: 9560264
PMCID: PMC20249
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Number of pages: 5263 - 5268
Language: English
Date published: 04/28/1998
Academic Unit: Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984656600402771

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