Hiraishi H, Terano A, Razandi M, Sugimoto T, Harada T, Ivey K J
Department of Medicine, Veterans Affairs Medical Center, Long Beach, California.
Gastroenterology. 1993 Mar;104(3):780-8. doi: 10.1016/0016-5085(93)91013-8.
Gastric epithelium is exposed to toxic, reactive oxygen species generated within the lumen. The present study examined the role of cellular iron and superoxide (O2-) in mediating hydrogen peroxide (H2O2)-induced damage to cultured gastric mucosal cells.
H2O2 was generated by glucose oxidase acting on b-D(+)glucose. Cytotoxicity was assessed by 51Cr release from prelabeled cells.
Deferoxamine (a chelator of Fe3+) prevented injury induced by H2O2, whether present before or during H2O2 production. In contrast, whereas the presence of phenanthroline (a chelator of Fe2+) during the cytotoxicity assay prevented damage, prior treatment with the agent did not; this suggested that cellular Fe3+ reduced to Fe2+ upon exposure to H2O2 is responsible for damage. Neither extracellular superoxide dismutase nor inhibitors of xanthine oxidase (a possible source of cellular O2- production) protected against H2O2. Further, protection by iron chelators was not associated with modulation of endogenous antioxidants.
Deferoxamine and phenanthroline protect cells from H2O2 by chelating stored iron (Fe3+) or reduced iron (Fe2+), respectively. Reduction of cellular Fe3+ appears to be a prerequisite for mediation of damage, but this reduction is independent of extracellular O2- or cellular xanthine oxidase-derived O2-.
胃上皮暴露于管腔内产生的有毒活性氧。本研究检测了细胞内铁和超氧化物（O₂⁻）在介导过氧化氢（H₂O₂）诱导的培养胃黏膜细胞损伤中的作用。
通过葡萄糖氧化酶作用于β-D(+)葡萄糖产生H₂O₂。通过预标记细胞释放⁵¹Cr来评估细胞毒性。
去铁胺（一种Fe³⁺螯合剂）可预防H₂O₂诱导的损伤，无论在H₂O₂产生之前还是期间存在。相反，虽然在细胞毒性测定期间菲咯啉（一种Fe²⁺螯合剂）的存在可预防损伤，但预先用该试剂处理则不能；这表明暴露于H₂O₂后细胞内Fe³⁺还原为Fe²⁺是造成损伤的原因。细胞外超氧化物歧化酶和黄嘌呤氧化酶（细胞O₂⁻产生的可能来源）抑制剂均不能保护细胞免受H₂O₂损伤。此外，铁螯合剂的保护作用与内源性抗氧化剂的调节无关。
去铁胺和菲咯啉分别通过螯合储存的铁（Fe³⁺）或还原铁（Fe²⁺）来保护细胞免受H₂O₂损伤。细胞内Fe³⁺的还原似乎是介导损伤的先决条件，但这种还原与细胞外O₂⁻或细胞黄嘌呤氧化酶衍生的O₂⁻无关。
