Potent anti‐inflammatory effects of an H 2 S‐releasing naproxen (ATB‐346) in a human model of inflammation

Autor: Parinaaz Jalali, Derek W. Gilroy, James Glanville, Julia D. Flint, John L. Wallace, Amit Patel, Alexander A. Maini, Ali A. Hosin
Rok vydání: 2021
Předmět:
Zdroj: The FASEB Journal. 35
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.201902918rr
Popis: ATB-346 is a hydrogen sulfide-releasing non-steroidal anti-inflammatory drug (H2 S-NSAID) derived from naproxen, which in preclinical studies has been shown to have markedly reduced gastrointestinal adverse effects. However, its anti-inflammatory properties in humans compared to naproxen are yet to be confirmed. To test this, we used a dermal model of acute inflammation in healthy, human volunteers, triggered by ultraviolet-killed Escherichia coli. This robust model allows quantification of the cardinal signs of inflammation along with cellular and humoral factors accumulating within the inflamed skin. ATB-346 was non-inferior to naproxen in terms of its inhibition of cyclooxygenase activity as well as pain and tenderness. ATB-346 significantly inhibited neutrophil infiltration at the site of inflammation at 4 h, compared to untreated controls. Subjects treated with ATB-346 also experienced significantly reduced pain and tenderness compared to healthy controls. Furthermore, both classical and intermediate monocyte subsets infiltrating the site of inflammation at 48 h expressed significantly lower levels of CD14 compared to untreated controls, demonstrating a shift toward an anti-inflammatory phenotype. Collectively, we have shown for the first time in humans that ATB-346 is potently anti-inflammatory and propose that ATB-346 represents the next generation of H2 S-NSAIDs, as a viable alternative to conventional NSAIDs, with reduced adverse effects profile.
Databáze: OpenAIRE
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