Hemin prevents cardiac and diaphragm mitochondrial dysfunction in sepsis

Gerald S. Supinski, Leigh A. Callahan

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Free radical-mediated mitochondrial dysfunction may play a role in the genesis of sepsis-induced multiorgan failure. Several cellular defenses protect against free radicals, including heme oxygenase. No previous study has determined if measures that increase heme oxygenase levels reduce mitochondrial dysfunction following endotoxin. The purpose of the present study was to determine if mitochondrial dysfunction following endotoxin (LPS) administration can be attenuated by administration of hemin, a pharmacological inducer of heme oxygenase. Blood pressure, heart rate, cardiac and diaphragm mitochondrial function, plasma nitrite/nitrate levels, and tissue markers of free radical generation were compared among rats given saline, LPS, hemin, or a combination of hemin and LPS. Endotoxin (LPS) administration produced large reductions in mitochondrial function (e.g., ATP production rate decreased in both tissues, P < 0.001). Administration of hemin increased tissue heme oxygenase levels, ablated LPS-induced alterations in mitochondrial function, attenuated LPS-induced increases in plasma nitrite/nitrate levels, and prevented LPS-mediated increases in tissue markers of free radical generation. These data indicate that tissue heme oxygenase levels modulate the degree of LPS-induced mitochondrial dysfunction. Measures that increase heme oxygenase levels may provide a means of reducing sepsis-induced mitochondrial dysfunction and tissue injury.

Original languageEnglish
Pages (from-to)127-137
Number of pages11
JournalFree Radical Biology and Medicine
Issue number1
StatePublished - Jan 1 2006

Bibliographical note

Funding Information:
Supported by NHLBI 69821 and 63698.

Copyright 2008 Elsevier B.V., All rights reserved.


  • Endotoxin
  • Free radicals
  • Heme oxygenase
  • Mitochondria
  • Sepsis

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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