Yajima N, Hiraishi H, Yamaguchi N, Ishida M, Shimada T, Terano A
Second Department of Internal Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
J Lab Clin Med. 1999 Oct;134(4):372-7. doi: 10.1016/s0022-2143(99)90151-8.
Helicobacter pylori (H. pylori) infection plays a role in the pathogenesis of peptic ulceration as well as active chronic gastritis. Possible mechanisms of H. pylori-induced mucosal injury include the generation of toxic monochloramine (NH2Cl) from oxidant (HOCl)--which is a product of activated neutrophils-and ammonia (NH3), which is a metabolite of H. pylori urease. To clarify mechanisms by which NH2Cl induces cytolysis, we determined the effects of glutathione (GSH) alteration and iron chelation on NH2Cl-induced damage in cultured rat gastric mucosal cells, because these are involved in oxidant injury. Cytotoxicity was quantified by chromium 51 release from prelabeled cells that were exposed to NH2Cl or hydrogen peroxide (H2O2). Although both NH2Cl and H2O2 caused a time-related and dose-dependent increase in 51Cr release, NH2Cl was more cytotoxic than H2O2. Pretreatment with extracellular GSH caused a right shift of the dose-response curve for NH2Cl, whereas pretreatment with diethyl maleate (a depletor of cellular GSH) rendered cells less resistant to NH2Cl. Iron chelation with 1,10-phenanthroline or deferoxamine failed to influence NH2Cl injury, whereas such treatment was protective against H2O2. Intracellular GSH seems to play an important role as a potent defense system against NH2Cl, as observed in H2O2-induced damage. However, the mechanisms of NH2Cl-induced damage seem to be distinctly different from cytolysis by H2O2 in terms of the mediation of cellular iron.
幽门螺杆菌（H. pylori）感染在消化性溃疡以及活动性慢性胃炎的发病机制中起作用。幽门螺杆菌诱导黏膜损伤的可能机制包括由氧化剂（次氯酸，HOCl，活化中性粒细胞的产物）生成有毒的一氯胺（NH2Cl）以及由幽门螺杆菌脲酶的代谢产物氨（NH3）。为阐明NH2Cl诱导细胞溶解的机制，我们确定了谷胱甘肽（GSH）改变和铁螯合对培养的大鼠胃黏膜细胞中NH2Cl诱导损伤的影响，因为这些与氧化损伤有关。细胞毒性通过暴露于NH2Cl或过氧化氢（H2O2）的预先标记细胞中铬51的释放来定量。虽然NH2Cl和H2O2均导致51Cr释放随时间和剂量依赖性增加，但NH2Cl的细胞毒性比H2O2更强。用细胞外GSH预处理导致NH2Cl剂量反应曲线右移，而用马来酸二乙酯（细胞内GSH的消耗剂）预处理使细胞对NH2Cl的抗性降低。用1,10 - 菲咯啉或去铁胺进行铁螯合未能影响NH2Cl损伤，而这种处理对H2O2有保护作用。如在H2O2诱导的损伤中所观察到的，细胞内GSH似乎作为针对NH2Cl的有效防御系统发挥重要作用。然而，就细胞铁的介导而言，NH2Cl诱导损伤的机制似乎与H2O2诱导的细胞溶解明显不同。
