HEMOGLOBIN-INDUCED AND MYOGLOBIN-INDUCED ACUTE RENAL-FAILURE IN RATS - ROLE OF IRON IN NEPHROTOXICITY
HEMOGLOBIN-INDUCED AND MYOGLOBIN-INDUCED ACUTE RENAL-FAILURE IN RATS - ROLE OF IRON IN NEPHROTOXICITY
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DOI：
10.1152/ajprenal.1988.255.3.f539
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发表时间：
1988-09-01
影响因子：
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通讯作者：
PALLER, MS
中科院分区：
文献类型：
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作者：
PALLER, MS
在缺血性急性肾功能衰竭中，氧自由基可介导损伤。此外，铁似乎在缺血肾脏再灌注过程中羟基自由基形成和脂质过氧化中起关键作用。为了确定铁是否可能在色素（血红素蛋白）诱导的急性肾功能衰竭中发挥类似的作用，我们研究了铁螯合剂去铁胺在两种实验模型中的作用，即在大鼠中，肌内注射甘油和静脉内输注血红蛋白，同时伴有缺血。肌内注射50%甘油（5 ml/kg）导致菊糖清除率下降至0.13 ± 0.15。0.03（SE）ml/min（正常值，1.0-1.2 ml/min）。在甘油注射时开始连续输注去铁胺显著减弱了这种肾功能不全。去铁胺处理的动物的菊粉清除率为0.37 ±。0.06 ml/min（P < 0.01）。甘油注射也与显著的脂质过氧化反应有关，以肾脏丙二醛含量测定。去铁胺处理的甘油注射大鼠的肾脏丙二醛含量与对照动物无显著差异。在另一个血红素色素诱导的肾损伤模型中，输注血红蛋白以产生血红蛋白尿。在血红蛋白输注后1小时菊粉清除率显著降低至0.84 ± 0.99。0.5 ml/min（P < 0.025）。输注去铁胺后，血红蛋白防止血红蛋白引起的菊粉清除率下降。肾缺血30分钟后输注血红蛋白导致更严重的肾功能不全，菊糖清除率为0.54 ± 0.5%。0.08在再灌注时输注去铁胺减弱了缺血和血红蛋白输注后肾小球滤过率的下降：菊粉清除率为1.04 ± 0.05。0.06（P < 0.005）。这些研究表明，在甘油注射或血红蛋白输注后，铁从血红蛋白（和肌红蛋白）中释放，并促进自由基形成、脂质过氧化和肾功能障碍。去铁胺通过结合游离铁并使其无毒来防止肾损伤。
In ischemic acute renal failure oxygen free radicals may mediate injury. In addition, iron appears to play a critical role in hydroxyl radical formation and lipid peroxidation during reperfusion of ischemic kidneys. To determine whether iron may play a similar role in pigment (heme protein)-induced acute renal failure, we studied the effects of the iron chelator deferoxamine in two experimental models of pigment-induced acute renal failure, intramuscular glycerol injection and intravenous hemogobin infusion without and with concurrent ischemia in the rat. Intramuscular injection of 50% glycerol (5 ml/kg) caused inulin clearance to fall to 0.13 .+-. 0.03 (SE) ml/min (normal value, 1.0-1.2 ml/min). Continuous infusion of deferoxamine beginning at the time of glycerol injection significantly attenuated this renal dysfunction. Deferoxamine-treated animals had an inulin clearance of 0.37 .+-. 0.06 ml/min (P < 0.01). Glycerol injection was also associated with significant lipid peroxidation, measured as renal malondialdehyde content. Deferoxamine-treated glycerol-injected rats had renal malondialdehyde content not significantly different from control animals. In another model of heme pigment-induced renal injury, hemoglobin was infused to produce hemoglobinuria. Inulin clearance 1 h after hemoglobin infusion was significantly reduced to 0.84 .+-. 0.5 ml/min (P < 0.025). Infusion of deferoxamine after hemoglobin prevented the hemoglobin-induced decrease in inulin clearance. Thirty minutes of renal ischemia followed by infusion of hemoglobin resulted in more severe renal dysfunction with inulin clearance of 0.54 .+-. 0.08 ml/min. Deferoxamine infused at the time of reperfusion attenuated the fall in glomerular filtration rate after ischemia and hemoglobin infusion: inulin clearance 1.04 .+-. 0.06 (P < 0.005). These studies suggest that after glycerol injection or hemoglobin infusion iron is released from hemoglobin (and myoglobin) and promotes free radical formation, lipid peroxidation, and renal dysfunction. Deferoxamine prevents renal injury by binding free iron and rendering it nontoxic.