(1)Effects of MGO: MGO (～1.0 mM) decreased cell viability, with enhancing depletion of intracellular GSH and apoptosis. Quenching endogenous H2O2 attenuated the toxic effect by MGO.(2)Effects of FA: The same levels of FA that MGO presented the toxicity increased cell viability by a dose-dependent manner. The effect was partly involved with the folate pathway since the co-administration of THF increased cell viability by FA. Quenching endogenous H2O2 attenuated the viable effect by FA.The cytotoxicity of MGO has been shown in cultured
Tofacitinib including U937 cells, as used in the present study [16], [18], [19], [20] and [21]. The basic mechanism has been thought to involve oxidative damage. Our focus has been on the fact that the chemical reaction of MGO and H2O2 generates radicals [30] and [31]. In cultured endothelium, administration of MGO increases reactive oxygen species (ROS) in a dose-dependent manner, but several antioxidants inhibits the increase in ROS and elimination of H2O2 by peg-CAT completely suppresses the increase of oxidative stress [46]. We therefore examined the effects of peg-CAT, an endogenous H2O2 quencher, on U937
cells exposed to MGO. The result showed that peg-CAT greatly reduced the decreased viability caused by MGO at 1.0 mM. Likewise, AG, an MGO scavenger [47], [48] and [49] reduced the decreased cell viability by MGO at 1.0 mM. Taken together the result of the decreased GSH levels on exposure to MGO, co-existences of MGO and H2O2 appear to be involved with the mechanisms of MGO cytotoxicity [15].
