The role of endogenous heme oxygenase in the initiation of liver injury following limb ischemia/reperfusion.

Journal Article (Journal Article)

BACKGROUND/AIMS: Heme oxygenase (HO) derived liver protection was tested in mice following 1 h bilateral hindlimb ischemia and either 1.5 or 3 h reperfusion. METHODS: Groups consisted of limb ischemia/reperfusion (I/R), sham (no I/R), I/R+chromium mesoporphyrin (I/R+CrMP;40 micromol/kg, i.p.), or I/R+hemin (10 mg/kg, i.p.). The vital dye propidium iodide (PI), was used to measure hepatocellular death (#/0.1 mm(3)), while the number of sinusoids perfused by red blood cells (SP(RBC)) were measured from the periportal (Pp) and pericentral (Pc) zones of liver acini using intravital microscopy. Whole organ injury was estimated from serum alanine aminotransferase (ALT). RESULTS: SP(RBC) reduced within 1.5 h with no further decline following 3 h. CrMP resulted in a dramatic loss of SP(RBC) following 3 h only. Hemin restored perfusion in both zones. Hepatocellular death and organ injury increased at 1.5 and 3 h. At 1.5 h, CrMP further increased cell death in the Pc zone, as well as whole organ injury, while hemin restored cell viability. Increased HO mRNA, protein and activity suggested induction within 3 h. CONCLUSIONS: HO does not protect perfusion during the early stage (1.5 h), but becomes increasingly important in preserving liver perfusion and cell viability during the later stage (3 h) of liver injury.

Full Text

Duke Authors

Cited Authors

  • Nie, RG; McCarter, SD; Harris, KA; Lee, PJ; Zhang, X; Bihari, A; Gray, D; Wunder, C; Brock, RW; Potter, RF

Published Date

  • May 2002

Published In

Volume / Issue

  • 36 / 5

Start / End Page

  • 624 - 630

PubMed ID

  • 11983445

International Standard Serial Number (ISSN)

  • 0168-8278

Digital Object Identifier (DOI)

  • 10.1016/s0168-8278(02)00025-9


  • eng

Conference Location

  • Netherlands