7,8-DIHYDRONEOPTERIN INHIBITS LOW-DENSITY-LIPOPROTEIN OXIDATION IN-VITRO - EVIDENCE THAT THIS MACROPHAGE SECRETED PTERIDINE IS AN ANTIOXIDANT

Neopterin and its reduced form, 7,8 dihydroneopterin ale pteridines re leased from macrophages and monocytes when stimulated with interferon gamma in vivo. The function of this response is unknown though there i s an enormous amount of information available on the use of these comp ounds as clinical markers of monocyte/macrophage activation. We have f ound that in vitro 7,8-dihydroneopterin dramatically increases, in a d ose dependent manner, the lag time of low density lipoprotein oxidatio n mediated by C++ ions or the peroxyl radical generator 2,2'-azobis (2 -amidino propane) dihydrochloride (AAPH). 7,8-Dihydroneopterin also in hibits AAPH mediated oxidation of linoleate. The kinetic of the inhibi tion suggests that 7,8-dihydroneopterin is a potent chain breaking ant ioxidant which functions by scavenging lipid peroxyl radicals. No anti -oxidant activity was observed in any of the oxidation systems studied with the related compounds neopterin and pterin.