Gressier B, Lebegue S, Brunet C, Luyckx M, Dine T, Cazin M, Cazin J C
Faculté de Pharmacie, Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Lille, France.
Pharmazie. 1994 Sep;49(9):679-81.
Polymorphonuclear neutrophils (PMNs) have the ability to liberate large amounts of reactive oxygen species like hydrogen peroxide. This free radicals release may have beneficial effect in chemotherapy but may also lead to cytotoxicity in case of prolongated inflammatory reaction. This in vitro study demonstrates that methotrexate (MTX), an anticancer drug, increases the amount of hydrogen peroxide released by stimulated PMNs in a dose-dependent manner with a maximum increase of 43.7% (i.e. 22 microM of hydrogen peroxide) for 500 microM of MTX. The mechanism which govern MTX reaction seems to be a result of an intracellular pro-oxidant mechanism by intervention on the oxidative metabolism of PMNs rather than a cell-free chemical interaction. Moreover, an association of MTX with mesna, an anti-oxidant drug, allowed to suppress the excess of hydrogen peroxide production. This association might be used in anticancer therapy, during oxidative burst, particularly when MTX is used in high concentrations, in order to limit toxic effects induced by free radicals.
多形核中性粒细胞（PMNs）能够释放大量活性氧，如过氧化氢。这种自由基的释放可能在化疗中产生有益作用，但在炎症反应延长的情况下也可能导致细胞毒性。这项体外研究表明，抗癌药物甲氨蝶呤（MTX）以剂量依赖的方式增加受刺激的PMNs释放的过氧化氢量，对于500微摩尔的MTX，过氧化氢的最大增加量为43.7%（即22微摩尔过氧化氢）。控制MTX反应的机制似乎是通过干预PMNs的氧化代谢而产生的细胞内促氧化机制，而不是无细胞化学相互作用。此外，MTX与抗氧化药物美司钠联合使用，可以抑制过氧化氢的过量产生。这种联合用药可能用于抗癌治疗中的氧化爆发期间，特别是当高浓度使用MTX时，以限制自由基诱导的毒性作用。
