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

• Published in: Journal of hepatology Vol. 36; no. 5; pp. 624 - 630
• Main Authors: Nie, Robert G., McCarter, Sarah D., Harris, Kenneth A., Lee, Patty J., Zhang, Xuchen, Bihari, Aurelia, Gray, Daryl, Wunder, Christian, Brock, Robert W., Potter, Richard F.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.05.2002; Elsevier
• Subjects: Alanine Transaminase - analysis; Animals; Biological and medical sciences; Blood Pressure; Cell Death; Digestive system; Extremities - blood supply; Heme oxygenase; Heme Oxygenase (Decyclizing) - genetics; Heme Oxygenase (Decyclizing) - metabolism; Heme Oxygenase-1; Hemin - pharmacology; Hepatocytes - cytology; Investigative techniques, diagnostic techniques (general aspects); Limb ischemia/reperfusion; Liver; Liver - blood supply; Liver - cytology; Liver - enzymology; Liver Circulation; Liver Diseases - metabolism; Male; Medical sciences; Membrane Proteins; Mesoporphyrins - pharmacology; Mice; Mice, Inbred C57BL; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Reperfusion Injury - metabolism; RNA, Messenger - analysis; Liver; Heme oxygenase; Limb ischemia/reperfusion; Enzyme; Rodentia; Heme oxygenase (decyclizing); Cardiovascular disease; Hepatic disease; Prevention; Vertebrata; Mammalia; Reperfusion; Ischemia; Mouse; Animal; Limb; Immunoblotting assay; Digestive diseases; Oxidoreductases; Mechanism of action; Protection test
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(02)00025-9

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 μmol/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.