Hemoglobin- and myoglobin-induced acute renal failure in rats: role of iron in nephrotoxicity

Am J Physiol. 1988 Sep;255(3 Pt 2):F539-44. doi: 10.1152/ajprenal.1988.255.3.F539.


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 hemoglobin 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 less than 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 less than 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 +/- 0.07 (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / physiopathology*
  • Animals
  • Deferoxamine / pharmacology
  • Disease Models, Animal
  • Glycerol
  • Hemoglobins*
  • Iron / toxicity*
  • Kidney / drug effects
  • Kidney / pathology
  • Lipid Peroxides / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Myoglobin*
  • Rats
  • Rats, Inbred Strains


  • Hemoglobins
  • Lipid Peroxides
  • Myoglobin
  • Malondialdehyde
  • Iron
  • Deferoxamine
  • Glycerol