HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Endogenous heme oxygenase induction is a critical mechanism attenuating apoptosis and restoring microvascular perfusion following limb ischemia/reperfusion.

AbstractBACKGROUND:
A protective role for endogenous heme oxygenase (HO) in the initiation of remote liver injury after limb ischemia/reperfusion has been established. This study expands on our previous work by investigating the role of endogenous HO on hepatocellular injury, hepatocyte death (necrotic and apoptotic), and microvascular perfusion at protracted post-reperfusion times.
METHODS:
Remote liver injury was studied after 1 hour of bilateral hind limb ischemia and 3, 6, or 24 hours of reperfusion in male C57BL6 mice. Inhibition of HO was achieved with the use of chromium mesoporphrin (CrMP). Established intravital videomicroscopy techniques were used to evaluate microvascular perfusion and hepatocyte death. Hepatocellular injury was quantified by serum alanine transaminase. Apoptosis was measured by using DNA laddering, Cell Death ELISA, and caspase-3 activity.
RESULTS:
Although significant perfusion deficits and hepatocellular injury/death occurred after 3 hours, progression of hepatocellular death beyond 6 hours was not observed. A transient increase in apoptosis was observed at 6 hours. By 24 hours, microvascular perfusion was completely restored. This lack of progression correlated with increased HO activity, observed throughout the protocol. Administration of CrMP reduced HO activity to sham nonstressed levels, and caused increased microvascular perfusion deficits, hepatocellular injury, and hepatocyte death over 24 hours. The transient increase in apoptosis was increased in duration and magnitude in CrMP-treated animals.
CONCLUSIONS:
These results suggest that endogenous HO activity prevents the progression of remote liver injury after limb ischemia/reperfusion.
AuthorsSarah D McCarter, Thelma G Akyea, Xiangru Lu, Aurelia Bihari, Jeffrey R Scott, Amit Badhwar, Alison A Dungey, Kenneth A Harris, Qingping Feng, Richard F Potter
JournalSurgery (Surgery) Vol. 136 Issue 1 Pg. 67-75 (Jul 2004) ISSN: 0039-6060 [Print] United States
PMID15232541 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Enzyme Inhibitors
  • Mesoporphyrins
  • chromium mesoporphyrin
  • Heme Oxygenase (Decyclizing)
Topics
  • Animals
  • Apoptosis (drug effects, physiology)
  • Cell Death (drug effects, physiology)
  • Enzyme Inhibitors (pharmacology)
  • Heme Oxygenase (Decyclizing) (antagonists & inhibitors, drug effects, physiology)
  • Hepatocytes (drug effects, physiology)
  • Hindlimb (blood supply)
  • Liver Diseases (etiology)
  • Male
  • Mesoporphyrins (pharmacology)
  • Mice
  • Microcirculation (drug effects, physiopathology)
  • Reperfusion Injury (complications, physiopathology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: