Hydroquinone modulates reactivity of peroxynitrite and nitric oxide production.
Peroxynitrite (ONOO(-)), a potent cytotoxic oxidant formed by the reaction of nitric oxide ((.-)NO) and superoxide radical ((.-)O(2)(-)), may be rapidly lethal in a cellular milieu due to oxidization and nitration processes. In the present study, hydroquinone displayed strong ONOO(-) scavenging activity and inhibitory effect on NO production in murine macrophage RAW264.7 cells. Hydroquinone strongly scavenged ONOO(-)induced dihydrorhodamine 123 oxidation in a dose-dependent manner compared with other reactive species such as (.-)O(2)(-) and (.-)NO. Hydroquinone also decreased levels of ONOO(-) induced nitrotyrosine of glutathione reductase and consequently prevented the enzyme from ONOO(-) induced damage. Furthermore, hydroquinone suppressed NO production, a cellular pathway for ONOO(-) formation, in lipopolysaccharide-activated RAW264.7 cells via inhibition of inducible NO synthase expression. The inhibitory effect by hydroquinone seems to be mediated by interruption of lipopolysaccharide-induced signalling such as activation of nuclear factor-kappaB and extracellular signalrelated kinases 1 and 2. The results suggest that hydroquinone may potently modulate reactivity of ONOO(-) and may therefore be a useful agent against ONOO(-) mediated diseases.
Kim
Ae Ra
AR
College of Pharmacy, Pusan National University, Pusan 609-735, South Korea.
Cho
Jae Youl
JY
Lee
Ji Yeon
JY
Choi
Jae Sue
JS
Chung
Hae Young
HY
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology*; D008070:Lipopolysaccharides; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology; D012235:Rhodamines; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D006873:Hydroquinones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D012235:Rhodamines; C058319:dihydrorhodamine 123; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D011794:Quercetin; D019001:Nitric Oxide Synthase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C031927:hydroquinone