Characterization of the protective effects of L-nitroarginine methyl ester(L-NAME) against the toxicity of sulphur mustard in vitro

The protective effects of L-nitroarginine methyl ester (L-NAME) against the toxicity of sulphur mustard (HD) was characterized in primary cultures of chick embryo forebrain neurons. These effects were not associated with the known nitric oxide synthase-inhibiting characteristics of this compound. No protection was evident in immature (1 day old) cultures. However, L-NAME p re-treatment resulted in a concentration-dependent protection against the t oxicity of HD in mature (5 days and older) cultures, with maximal protectio n reaching greater than 220% at 5 mM L-NAME in terms of increasing the LC50 of control HD-treated cultures. Maximal protective effects were also achie ved when L-NAME treatment was delayed up to 3 h post-HD exposure. These eff ects were reduced by 5 h and absent when the L-NAME was added to the cultur es 8 h after HD exposure. Protection against the toxicity of HD was depende nt on the continued presence of L-NAME in the medium and was persistent up to 48 h after HD exposure. This compound is one of the most effective drugs yet identified in protecting against the toxicity of HD and is the only on e that exerts its effects therapeutically. (C) 1998 Published by Elsevier S cience Ireland Ltd. All rights reserved.