Natural antioxidants enhance and prolong the oxyradical/NO-related suppression by dexamethasone of ischemic and histamine paw edema in mice

Dexamethasone (0.1 mg/kg, s.c.) suppressed 2, 22, 12, 6, and 4% of ischemic paw edema of mice at 1, 3, 6, 18, and 40 h. Various antioxidants when given with 0.1 mg/kg Dex enhanced and prolonged the suppression. For example, 30 mg/kg of tannic acid induced suppression of 6, 52, 59, 42 and 27%, whereas no increase of Dex suppression at 1 h was observed with any of the antioxidants tested. The prolonging effect of antioxidants may be due to the change of glucocorticoid (GC) receptor signaling under new redox stare, because oxyradicals modified the suppression, whereas nitric oxide (NO) showed no effect on Dex suppression enhanced by antioxidants. ED30 (mg/kg, i.p.) at 6 h after Dex was: morin (0.02) > alpha-tocopherol (0.03) > tannic acid (0.12) > rutin (0.2) = bilirubin (0.2) > beta-carotene (0.3) much greater than quercetin (6) > melatonin (8) > ascorbic acid (12), whereas none of the antioxidants alone afforded more than 10% suppression even at 30 mg/kg. Similar Dex plus antioxidant actions were observed in histamine paw edema. Clinical trials of nontoxic natural antioxidants might be successful when coinjected with low dose of GC which shows very little side effects.