EXOGENOUS IRON AND GAMMA-IRRADIATION INDUCE NO-SYNTHASE SYNTHESIS IN MOUSE-LIVER

Protein synthesis inhibitor (cycloheximide, CHI) and exogenous antioxi dant (phenazan) suppress the synthesis of NO in mouse liver in vivo wh ich is induced by administration to the animals of gamma-irradiation, bacterial lipopolysaccharide (LPS), or Fe2+-citrate together with LPS. Biosynthesis of NO was monitored by the ESR signal of paramagnetic mo nonitrosyl iron complexes with the exogenous ligand diethyldithiocarba mate (MNIC-DETC) 30 min after addition of the ligand. The complexes ar ise from NO binding to DETC complexes with exogenous and endogenous Fe 2+ which act as selective NO traps. The enhancement of NO biosynthesis after gamma-irradiation or LPS or LPS + Fe2+-citrate is apparently du e to the induction of the synthesis of NO-synthase, which is inhibited by cycloheximide. This process is triggered by reactive oxygen specie s, presumably through the activation of the transcription factor prote in NFkB. The accumulation of free radical oxygen species is inhibited by the antioxidant phenazan.