Gentamicin nephrotoxicity. II. Definition of conditions necessary to induce acquired insensitivity.
Gentamicin nephrotoxicity. II. Definition of conditions necessary to induce acquired insensitivity.
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庆大霉素肾毒性。
DOI：
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发表时间：
1982
期刊：
影响因子：
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通讯作者：
William M. Bennett
中科院分区：
文献类型：
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作者：
W. Elliott;D. Houghton;David N. Gilbert;J. Baines;William M. Bennett
Fischer 344大鼠在广泛组织学再生的情况下，在发生组织学急性小管坏死后，治疗10至14天后，对庆大霉素肾毒性作用产生获得性不敏感。为了确定氨基糖苷暴露、坏死和再生在诱导不敏感中的相对重要性，我们检查了先前非氨基糖苷介导的肾小管坏死、先前非坏死性氨基糖苷暴露和单侧nx诱导的肾小管增生对庆大霉素毒性的影响。重铬酸钾与庆大霉素在肾皮质相同部位引起肾小管坏死，预处理可降低庆大霉素介导的Scr升高，但对庆大霉素相关的肾小管功能障碍或结构损伤影响甚微。奈替米星预处理不会引起肾小管坏死，但增加了肾脏对庆大霉素的敏感性；毒性发生得更早，也更严重。先前的单侧Nx对庆大霉素相关功能障碍的易感性没有明显的影响，但组织学肾小管上皮的再生和功能障碍的恢复发生得更早。这些结果表明，坏死和/或再生是庆大霉素不敏感发展的主要先决条件，而不敏感的发生与坏死和再生的出现在时间上有关。然而，非氨基糖苷介导的坏死和再生不能完全重建不敏感，这表明暴露于庆大霉素也是必要的。
Acquired insensitivity to the nephrotoxic effects of gentamicin develops in Fischer 344 rats after 10 to 14 days' treatment after development of histologic acute tubular necrosis in a setting of extensive histologic regeneration. To determine the relative importance of aminoglycoside exposure, necrosis, and regeneration in the induction of insensitivity, we examined the effect on gentamicin toxicity of prior non-aminoglycoside-mediated tubular necrosis, antecedent nonnecrotizing aminoglycoside exposure, and unilateral Nx-induced renal tubular hyperplasia. Pretreatment with potassium dichromate, which causes tubular necrosis in the same part of the renal cortex as gentamicin, reduced gentamicin-mediated elevation of Scr but had little effect on gentamicin-related tubular dysfunction or structural damage. Pretreatment with netilmicin, which does not cause tubular necrosis, increased the sensitivity of the kidney to gentamicin; toxicity occurred earlier and was more severe. Antecedent unilateral Nx had no demonstrable effect on susceptibility to gentamicin-associated dysfunction, but histologic renal tubular epithelial regeneration and recovery from dysfunction occurred earlier, These results suggest that necrosis and/or regeneration is the major prerequisite for development of gentamicin insensitivity and that the onset of insensitivity is temporally related to the appearance of necrosis and regeneration. However, non-aminoglycoside-mediated necrosis and regeneration fail to fully-re-create insensitivity, suggesting that exposure to gentamicin is also necessary.