The effect of amiodarone and/or antioxidant treatment on splenocyte blast transformation

Previous studies have shown that free radical reactions may play an importa nt role in the pathogenesis of the adverse effects of the antiarrhythmic ag ent amiodarone. The aim of this study was to investigate the role of free r adical reactions in amiodarone-induced changes in the cell-mediated immune response. Therefore, we investigated the effects of amiodarone alone and in combination with either vitamin E or silymarin on (a) spontaneous blast tr ansformation of splenocytes, (b) concanavalin A (con A)-induced proliferati on of splenocytes at three different lectin concentrations, and (c) the con tent of conjugated dienes in liver homogenate. Forty-eight male Fischer 344 rats were randomized to one of the following groups: 1, control; 2, amioda rone; 3, vitamin E; 4, amiodarone + vitamin E; 5, silymarin; 6, amiodarone + silymarin. The con A-induced splenocyte proliferation was significantly d ecreased in amiodarone-treated rats at all three lectin concentrations. In the amiodarone-treated group, the change of spontaneous blast transformatio n was not significantly different from the control. In groups treated with amiodarone plus either antioxidant, both the spontaneous and con A-induced splenocyte proliferation were significantly increased compared with the ami odarone-treated group, and were similar to those in the control group. Amio darone treatment significantly increased, and both silymarin and vitamin E combined with amiodarone significantly decreased, the conjugated diene cont ent of liver homogenate compared with amiodarone treatment alone. In conclu sion, free radicals generated by amiodarone may be implicated in the advers e effects of amiodarone on cell-mediated immune response, and antioxidants applied together with amiodarone may protect against or reduce both the unf avorable immunological effects of amiodarone and amiodarone toxicity. (C) 2 001 Elsevier Science B.V. All rights reserved.