The influence of antioxidants and cycloheximide on the level of nitric oxide in the livers of mice in vivo.

When injected into mice prior to the NO generation increase induced with lipopolysaccharide (LPS) from Escherichia coli, exogenous antioxidants diethyldithiocarbamate (DETC) or phenazan (sodium 3.5-di-tert-butyl-4-oxiphenylpropionate) as well as the inhibitor of protein biosynthesis, cycloheximide (CHI) attenuated the NO production in mouse liver in vivo. These data demonstrated the key role of free radicals, which were likely, active oxygen species, in the synthesis of inducible NO-synthase (iNOS) responsible for the NO production in this organ. Similar effects of phenazan and CHI were observed in livers of mice treated with gamma-irradiation or LPS + Fe(2+)-citrate, which suggested that these treatments also induced 1NOS synthesis through initiating the action of active oxygen species. The rate of NO synthesis was estimated by accumulation of paramagnetic mononitrosyl iron complexes with DETC (MNIC-DETC) detected using the EPR method. The formation of MNIC-DETC complexes was found in the brain of mice pre-treated with LPS + Fe(2+)-citrate which seemed to be due to iNOS synthesis stimulated by this treatment.