Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat

Karl A Nath, Gyorgy Balla, Gregory M. Vercellotti, Jozsef Balla, Harry S. Jacob, Michael D. Levin, Mark E. Rosenberg

Research output: Contribution to journalArticle

547 Citations (Scopus)

Abstract

Heme proteins such as myoglobin or hemoglobin, when released into the extracellular space, can instigate tissue toxicity. Myoglobin is directly implicated in the pathogenesis of renal failure in rhabdomyolysis. In the glycerol model of this syndrome, we demonstrate that the kidney responds to such inordinte amounts of heme proteins by inducing the heme-degradative enzyme, heme oxygenase, as well as increasing the synthesis of ferritin, the major cellular repository for iron. Prior recruitment of this response with a single preinfusion of hemoglobin prevents kidney failure and drastically reduces mortality (from 100% to 14%). Conversely, ablating this response with a competitive inhibitor of heme oxygenase exacerbates kidney dysfunction. We provide the first in vivo evidence that induction of heme oxygenase coupled to ferritin synthesis is a rapid, protective antioxidant response. Our findings suggest a therapeutic strategy for populations at a high risk for rhabdomvolysis.

Original languageEnglish (US)
Pages (from-to)267-270
Number of pages4
JournalJournal of Clinical Investigation
Volume90
Issue number1
StatePublished - 1992
Externally publishedYes

Fingerprint

Heme Oxygenase (Decyclizing)
Rhabdomyolysis
Hemeproteins
Myoglobin
Ferritins
Renal Insufficiency
Hemoglobins
Kidney
Extracellular Space
Heme
Glycerol
Iron
Antioxidants
Mortality
Enzymes
Population
Therapeutics

Keywords

  • Crush
  • Ferritin
  • Hemoglobin
  • Kidney
  • Oxidants
  • Syndrome

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Nath, K. A., Balla, G., Vercellotti, G. M., Balla, J., Jacob, H. S., Levin, M. D., & Rosenberg, M. E. (1992). Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. Journal of Clinical Investigation, 90(1), 267-270.

Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. / Nath, Karl A; Balla, Gyorgy; Vercellotti, Gregory M.; Balla, Jozsef; Jacob, Harry S.; Levin, Michael D.; Rosenberg, Mark E.

In: Journal of Clinical Investigation, Vol. 90, No. 1, 1992, p. 267-270.

Research output: Contribution to journalArticle

Nath, KA, Balla, G, Vercellotti, GM, Balla, J, Jacob, HS, Levin, MD & Rosenberg, ME 1992, 'Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat', Journal of Clinical Investigation, vol. 90, no. 1, pp. 267-270.
Nath, Karl A ; Balla, Gyorgy ; Vercellotti, Gregory M. ; Balla, Jozsef ; Jacob, Harry S. ; Levin, Michael D. ; Rosenberg, Mark E. / Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 1. pp. 267-270.
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