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 pre-treatment resulted in a concentration-dependent protection against the toxicity of HD in mature (5 days and older) cultures, with maximal protection 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 achieved when L-NAME treatment was delayed up to 3 h post-HD exposure. These effects were reduced by 5 h and absent when the L-NAME was added to the cultures 8 h after HD exposure. Protection against the toxicity of HD was dependent 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 one that exerts its effects therapeutically.
Sawyer
T W
TW
Therapy Group, Medical Countermeasures Section, Defence Research Establishment Suffield, Alberta, Canada. thomas.sawyer@dres.dnd.ca
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D002642:Chick Embryo; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D009151:Mustard Gas / Q000633:toxicity*; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004791:Enzyme Inhibitors; D009151:Mustard Gas; D019331:NG-Nitroarginine Methyl Ester