| Hemoglobin is the protein of carrying oxygen in higher organisms.Under thecondition of oxidative stress, the reaction between hemoglobin with peroxider canform high cytotoxicity ferryl Hb, and produce toxic to the body. In this paper, wechose ascorbic acid and nitrite to study their ef ciencies on hemoglobin-inducedredox reaction. The main research contents include the following two aspects:The first chapter: the impact of ascorbate acid at pharmacologic concentrationson hemoglobin-modulated human hepatoma HepG2cell survival was investigated. Itwas found that although ascorbate at the low pharmacologic concentration (0.5mM)alone exhibited unobvious effect on cancer cell viability, it effectively inhibitedhemoglobin (10μM)-induced cancer cell proliferation. The mechanism of this cytoto-xicity was based on the rapid production of extracellular hydrogen peroxide (H2O2)and involved transition iron. The influence of ascorbate on hemoglobin dependentredox reactions (i.e. the oxidative stability of Hb and its cytotoxic ferryl intermediate)was further investigated to illustrate the reaction mechanism of ascorbate toxicity.These results further confirmed that ascorbate could possess anti-cancer activitythrough interfering in Hb-dependent redox reactions.The second chapter: we studied the effect of nitrite on hypochlorous acid inducedheme destruction and free iron release. The mechanism by which nitrite preventsHOCl-mediated Hb heme destruction is by direct scavenging of HOCl and/or throughthe destabilization of the higher Hb oxidative states intermediates. It’s shown thatnitrite can exert its protective effect by inhibiting HOCl-mediated heme destruction ofhemoproteins and subsequent free iron release. |
PDF Full Text Request