Autor: |
Thomas W. Johnson, James Holt, Anna Kleyman, Shengyu Zhou, Eva Sammut, Vito Domenico Bruno, Charlotte Gaupp, Giacomo Stanzani, John Martin, Pietro Arina, Julia Deutsch, Raimondo Ascione, Mervyn Singer, Alex Dyson |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
Redox Biology, Vol 73, Iss , Pp 103167- (2024) |
Druh dokumentu: |
article |
ISSN: |
2213-2317 |
DOI: |
10.1016/j.redox.2024.103167 |
Popis: |
Sulfide-releasing compounds reduce reperfusion injury by decreasing mitochondria-derived reactive oxygen species production. We previously characterised ammonium tetrathiomolybdate (ATTM), a clinically used copper chelator, as a sulfide donor in rodents. Here we assessed translation to large mammals prior to clinical testing. In healthy pigs an intravenous ATTM dose escalation revealed a reproducible pharmacokinetic/pharmacodynamic (PK/PD) relationship with minimal adverse clinical or biochemical events. In a myocardial infarction (1-h occlusion of the left anterior descending coronary artery)-reperfusion model, intravenous ATTM or saline was commenced just prior to reperfusion. ATTM protected the heart (24-h histological examination) in a drug-exposure-dependent manner (r2 = 0.58, p |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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