title: Oltipraz inhibits inducible nitric oxide synthase in vitro and inhibits nitric oxide production in activated microglial cells.
abstract: The clinically relevant drug oltipraz (OPZ) has previously been shown to inhibit cytochrome P450 enzymes [Chem. Res. Toxicol. 13 (2000) 245]. The current study reveals that OPZ is also able to inhibit *NO formation by purified inducible nitric oxide synthase (iNOS) but not by neuronal nitric oxide synthase in hemoglobin assays. The inhibition of iNOS by OPZ is reversible and competitive with an IC(50) of 5.9 microM and Ki of 0.6 microM. In murine BV-2 microglial cells, an immortalized cell line that produces *NO in response to lipopolysaccharide (LPS), OPZ is able to block the formation of nitrite in LPS treated cells. The inhibitory effect of OPZ on LPS treated cells is not due to cell toxicity. Finally, treatment of cells with OPZ does not induce or suppress expression of iNOS protein as shown by Western blot analysis.
authors.affiliation: Department of Chemistry, Kalamazoo College, Kalamazoo, MI 49006, USA. lfurge@kzoo.edu
authors.forename: Laura Lowe
authors.initials: LL
authors.lastname: Furge
authors.forename: Patrice R
authors.initials: PR
authors.lastname: Fields
authors.forename: Whitney E
authors.initials: WE
authors.lastname: Goode
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Konwinski
authors.forename: Michael C
authors.initials: MC
authors.lastname: Tressler
authors.forename: Regina
authors.initials: R
authors.lastname: Stevens-Truss
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D011719:Pyrazines / Q000737:chemistry* / Q000494:pharmacology*; D013871:Thiones; D013876:Thiophenes
chemical_list: D004791:Enzyme Inhibitors; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; D009569:Nitric Oxide; C026209:oltipraz; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse