Hagiwara K, Ozasa H, Ota K, Ichikawa T
Division of Applied Food Research, National Institute of Health and Nutrition, Tokyo, Japan.
Nihon Jinzo Gakkai Shi. 1994 Oct;36(10):1082-9.
Four-week-old Wistar male rats were fed a vitamin E (VE)-deficient diet for 8 weeks, followed by intraperitoneal injection of DL-buthionine- [S, R] -sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, at the dose of 1 mmol/kg body weight. As we reported previously, GSH depletion by administration of BSO induced acute tubular necrosis in the kidney of VE-deficient rats and was accompanied by decrease of renal TBA value and marked increase of renal lipofuscin content. In this study, we examined the effect of administration of AsA or Trolox C on these kidney injuries. AsA or Trolox C treatment increased renal GSH content and inhibited the increase of renal lipofuscin production. The increase of BUN and creatinine levels and LDH activity in the sera of rats administered BSO were inhibited by AsA or Trolox C treatment. AsA treatment completely protected the necrosis of epithelia of proximal renal tubules. These results suggest that GSH has an important role in preventing lipofuscin production through the reaction of lipid peroxides with amino acids. AsA spares GSH indicating that these compounds have similar antioxidant actions and that AsA can serve as an essential antioxidant in the presence of severe GSH deficiency.
将四周龄的雄性Wistar大鼠喂食维生素E（VE）缺乏的饲料8周，随后腹腔注射γ-谷氨酰半胱氨酸合成酶抑制剂DL-丁硫氨酸-[S，R]-亚砜亚胺（BSO），剂量为1 mmol/kg体重。正如我们之前报道的，给予BSO导致VE缺乏大鼠肾脏中谷胱甘肽（GSH）耗竭，进而诱发急性肾小管坏死，同时伴有肾脏硫代巴比妥酸（TBA）值降低和肾脏脂褐素含量显著增加。在本研究中，我们检测了给予抗坏血酸（AsA）或生育三烯酚（Trolox C）对这些肾脏损伤的影响。AsA或Trolox C治疗增加了肾脏GSH含量，并抑制了肾脏脂褐素生成的增加。AsA或Trolox C治疗抑制了给予BSO大鼠血清中尿素氮（BUN）和肌酐水平以及乳酸脱氢酶（LDH）活性的增加。AsA治疗完全保护了近端肾小管上皮细胞的坏死。这些结果表明，GSH在通过脂质过氧化物与氨基酸的反应预防脂褐素生成中具有重要作用。AsA可节省GSH，表明这些化合物具有相似的抗氧化作用，并且在严重GSH缺乏的情况下AsA可作为一种必需的抗氧化剂。
