Biochemical and toxicological evaluation of agent-cofactor reactivity as a mechanism of action for osteolathyrism.

摘要: In vitro reactivity for each of four osteolathyrogens with a model compound the lysyl oxidase (LO) cofactor was evaluated and coupled mixture toxicity testing to evaluate agent-cofactor as potential mechanism action osteolathyrism. Reactivity (mLTQ: 4-butylamino-5-methyl-o-quinone), two ureides, semicarbazide (SC) thiosemicarbazide (TSC), aminonitriles, aminoacetonitrile (AAN) β-aminopropionitrile (βAPN), assessed using UV–vis spectrophotometry; both in absence presence Cu(II)–bipyridine (bipy) complex. Two sets experiments were conducted frog embryo assay that incidence osteolathyrism notochord tadpoles after 96-h exposure. The resulting concentration–response curves set (χ2 goodness-of-fit test) against theoretical combined effects models: dose–addition independence, determine effect osteolathyrogen combination. agents SC, TSC AAN showed rapid, irreversible mLTQ, Cu(II)–bipy complex, indicated by bleaching mLTQ peak (504 nm) formation an adduct at 350 nm. βAPN no apparent prolonged incubation whether complex present or not. After (24–144 h) new formed nm, suggesting reacts weakly cofactor, but manner different from other examined. tests dose-additive SC:TSC, AAN:SC AAN:SC:TSC mixtures (0.1