Fructose-1,6-diphosphate enhanced oxyradicals and nitric oxide-dependent suppressions by dexamethasone of ischemic and histamine paw edema of mice.
Dexamethasone (Dex, 0.1 mg/kg, s.c.) suppressions of ischemic paw edema in mice at 1, 3, 6, 8, 18 hr were; 2, 22, 12, 11, 7%. Dex suppression in fructose-1,6-diphosphate (FDP, 100 mg/kg, i.p.)-treated mice were; 5, 49, 51, 42, 33%. Suppressions by this dose of FDP alone were less than 10% during 0-18 hr. ED30 at 6 hr of Dex +/- FDP was: 80 versus 500 mg/kg in ischemic-, and 5 versus 30 mg/kg in histamine edema. Endogenous oxyradicals or NO and protein synthesis were essential for suppressions. FDP may not change glucocorticoid receptor (GR) conformation, but increase ATP-dependent GR recycling efflux from nucleus. FDP is possible to supply this ATP. Clinical trial of FDP with low dose of Dex seems advantageous.
Oyanagui
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2nd Pharmacology, Drug Development Laboratories of Fujisawa Pharmaceutical Co., Osaka, Japan.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005528:Foot / Q000098:blood supply*; D005635:Fructosediphosphates / Q000494:pharmacology*; D006632:Histamine; D007511:Ischemia / Q000188:drug therapy*; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D005635:Fructosediphosphates; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D003907:Dexamethasone; D006632:Histamine; D000255:Adenosine Triphosphate; C029063:fructose-1,6-diphosphate