Experimental gentamicin nephrotoxicity: effect of streptozotocin-induced diabetes.
Experimental gentamicin nephrotoxicity: effect of streptozotocin-induced diabetes.
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实验性庆大霉素肾毒性：链脲佐菌素诱导的糖尿病的作用。
DOI：
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发表时间：
1985
影响因子：
3.5
通讯作者：
W. Bennett
中科院分区：
文献类型：
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作者：
W. Elliott;D. Houghton;David Gilbert;J. Baines;W. Bennett
为了确定糖尿病对庆大霉素肾毒性的影响，我们用链脲佐菌素22 mg/kg（DM大鼠）处理雄性F344大鼠。将糖尿病大鼠与对照组（C）和非糖尿病大鼠进行比较，观察给药渗透性利尿剂异山梨醇以模拟糖尿性利尿（C/I）。基线C/I肾功能和组织学与C无差异。然而，与C和C/I相比，DM大鼠的基线菊粉清除率（CIN）低20%，肾皮质切片对氨基马尿酸盐的摄取减少。DM大鼠还出现C或C/I中未观察到的肾小管上皮发育不良灶。庆大霉素以40 mg/kg-天的剂量给予C和C/I大鼠，以32 mg/kg-天的剂量给予DM大鼠，以调整基线CIN。急性肾小管坏死，与CIN和肾皮质对氨基马尿酸盐和N-甲基烟酰胺摄取的抑制相关，在所有三组中均发生。C和C/I之间没有差异。但DM大鼠急性肾小管坏死和功能障碍程度较C和C/I轻。糖尿病大鼠肾皮质庆大霉素蓄积也比C或C/I慢，糖尿病大鼠肾皮质庆大霉素随时间的变化遵循不同的模式。这些结果表明：1）DM大鼠中庆大霉素损伤的减轻可能与肾皮质庆大霉素蓄积减少有关，2）这种蓄积减少可能是由于链脲佐菌素介导的轻微基线肾小管损伤或糖尿病状态所致，3）渗透性利尿不能解释DM中肾损伤的减轻。
To determine the effect of diabetes mellitus on gentamicin nephrotoxicity we treated male F344 rats with streptozotocin 22 mg/kg (DM rats). DM rats were compared to controls (C) and nondiabetic rats ingesting the osmotic diuretic isosorbide administered to simulate glycosuric diuresis (C/I). Base-line C/I renal function and histology did not differ from C. However, in DM rats base-line inulin clearance (CIN) was 20% lower, and renal cortical slice uptake of p-aminohippurate was reduced compared to C and C/I. DM rats also had foci of renal tubular epithelial dysplasia not seen in C or C/I. Gentamicin was administered at 40 mg/kg-day to C and C/I and 32 mg/kg-day to DM rats to adjust for base-line CIN. Acute tubular necrosis, associated with depression of CIN and renal cortical p-aminohippurate and N-methylnicotinamide uptake, developed in all three groups. There were no differences between C and C/I. However, the degree of acute tubular necrosis and dysfunction was less in DM rats than C and C/I. Renal cortical gentamicin accumulation was also slower in DM than either C or C/I, and changes in renal cortical gentamicin over time followed a different pattern in DM rats. These results indicate that 1) attenuation of gentamicin injury in DM rats may be related to reduced accumulation of gentamicin by the renal cortex, 2) this reduced accumulation may be due to subtle baseline tubular injury mediated by streptozotocin or the diabetic state, and 3) osmotic diuresis does not account for attenuation of renal injury in DM.