IRON POTENTIATES BACTERIAL LIPOPOLYSACCHARIDE-INDUCED NITRIC-OXIDE FORMATION IN ANIMAL ORGANS

Administration of an Fe2+-citrate complex to mongrel mice pretreated w ith lipopolysaccharide (LPS) from Salmonella typhosa increased LPS-ind uced NO formation in vivo in the liver, intestine, lung, heart, kidney and spleen by 10-20-fold. This process was monitored by the intensity of the EPR signal due to mononitrosyl iron complex (MNIC) formation w ith exogenous diethyldithiocarbamate (DETC) recorded in the tissues. T he NO synthase inhibitor, N(G)-nitro-L-arginine, prevented this comple x formation in the liver of mice treated with both LPS and Fe2+-citrat e complex. Thus, administration of LPS and Fe2+-citrate complex to mic e induced NO biosynthesis in this tissue via an L-arginine-dependent p athway, presumably by facilitating the entry of Ca2+ ions into NO-prod ucing cells through Fe2+-induced cell membrane lesions.