The Synthetic Myeloperoxidase Inhibitor AZD3241 Ameliorates Dextran Sodium Sulfate Stimulated Experimental Colitis

Autor: Gulfam Ahmad, Belal Chami, Yuyang Liu, Angie L. Schroder, Patrick T. San Gabriel, Antony Gao, Genevieve Fong, XiaoSuo Wang, Paul K. Witting
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 11 (2020)
Druh dokumentu: article
ISSN: 1663-9812
DOI: 10.3389/fphar.2020.556020
Popis: Chronic inflammatory bowel disease (IBD) is a condition with multifactorial pathophysiology. To date, there is no permanent cure and the disease is primarily managed by immunosuppressive drugs; long-term use promotes serious side effects including increased risk malignancies. The current study aimed to target neutrophil-myeloperoxidase, a key contributor to the pathogenesis of IBD, through the use of AZD3241that inhibits extracellular myeloperoxidase. Experimental colitis was induced in C57BL/6 male mice by 2% dextran sodium sulfate in drinking water ad libitum over 9 days. Mice received either normal drinking water and peanut butter (control), 2% DSS in drinking water and peanut butter or 2% DSS in drinking water and AZD3241 (30 mg/kg) dispersed in peanut butter daily for 9 days. Administered AZD3241 attenuated body weight loss (10% p
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