Nishimura Y, Nakayama M, Sato T, Tomita K, Inoue M
Department of Medicine, Kumamoto University Medical School, Japan.
Nephron. 1995;70(4):460-5. doi: 10.1159/000188646.
To know the possible involvement of reactive oxygen species and the site(s) of their action in puromycin aminonucleoside (PAN)-induced renal injury, two types of superoxide dismutase (SOD) derivatives were synthesized: one (SM-SOD) circulates bound to albumin with a half-life of 6 h and the other (AH-SOD) linked with hexamethylenediamines rapidly undergoes glomerular filtration and accumulates in renal proximal tubule cells without being excreted in urine. When injected intravenously to the rat, PAN induced a marked proteinuria, increased plasma levels of cholesterol and triglyceride, and suppressed the growth of animals. Intravenously administered SM-SOD significantly inhibited such changes induced by PAN. However, native SOD which rapidly undergoes urinary excretion failed to inhibit the renal injury caused by PAN. Though AH-SOD markedly accumulated in renal proximal tubule cells, it also failed to inhibit the renal injury. These results suggested that superoxide and/or its hazardous metabolite(s) in and around the renal glomerulus, but not in tubule cells, may play critical roles in the pathogenesis of PAN-induced renal injury.
为了解活性氧及其作用位点在嘌呤霉素氨基核苷（PAN）诱导的肾损伤中可能的参与情况，合成了两种超氧化物歧化酶（SOD）衍生物：一种（SM-SOD）与白蛋白结合循环，半衰期为6小时，另一种（AH-SOD）与六亚甲基二胺连接，迅速经肾小球滤过并积聚在肾近端小管细胞中，而不随尿液排出。给大鼠静脉注射时，PAN诱导明显的蛋白尿、血浆胆固醇和甘油三酯水平升高，并抑制动物生长。静脉注射SM-SOD可显著抑制PAN诱导的这些变化。然而，迅速经尿液排泄的天然SOD未能抑制PAN引起的肾损伤。尽管AH-SOD在肾近端小管细胞中显著积聚，但它也未能抑制肾损伤。这些结果表明，肾小球内及周围而非肾小管细胞中的超氧阴离子和/或其有害代谢产物可能在PAN诱导的肾损伤发病机制中起关键作用。
