Does inhibition of aldose reductase contribute to the anti-inflammatory action of setipiprant?
Language English Country Czech Republic Media print-electronic
Document type Journal Article
PubMed
28406694
DOI
10.33549/physiolres.933516
PII: 933516
Knihovny.cz E-resources
- MeSH
- Aldehyde Reductase antagonists & inhibitors metabolism MeSH
- Anti-Inflammatory Agents chemistry pharmacology MeSH
- Indoles chemistry pharmacology MeSH
- Enzyme Inhibitors metabolism pharmacology MeSH
- Rats MeSH
- Humans MeSH
- NADP metabolism MeSH
- Naphthalenes chemistry pharmacology MeSH
- Rats, Wistar MeSH
- Molecular Docking Simulation methods MeSH
- Binding Sites physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido(4,3-b)indol-5(2H)-yl)acetic acid MeSH Browser
- AKR1B1 protein, human MeSH Browser
- Aldehyde Reductase MeSH
- Anti-Inflammatory Agents MeSH
- Indoles MeSH
- Enzyme Inhibitors MeSH
- NADP MeSH
- Naphthalenes MeSH
The aim of this study was to investigate aldose reductase inhibitory action of setipiprant as a potential additional mechanism contributing to its anti-inflammatory action. Aldose reductase activity was determined by spectrophotometric measuring of NADPH consumption. Setipiprant was found to inhibit aldose reductase/NADPH-mediated reduction of 4-hydroxynonenal, 4-hydroxynonenal glutathione and prostaglandin H2 substrates, all relevant to the process of inflammation. Molecular modeling simulations into the aldose reductase inhibitor binding site revealed an interaction pattern of setipiprant. Considering multifactorial etiology of inflammatory pathologies, it is suggested that, in addition to the antagonizing prostaglandin D2 receptor, inhibition of aldose reductase may contribute to the reported anti-inflammatory action of setipiprant.
Institute of Experimental Pharmacology and Toxicology Slovak Academy of Sciences Bratislava Slovakia
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