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Metalloporphyrins, used for HO‐1 Inhibition, Themselves Affect Hepatic Microcirculation, Liver Function, and Hepatocellular Integrity
Author(s) -
SCHEINGRABER STEFAN,
MESSNER SVEN,
MATT SUSANNE,
ABEL KATHRIN,
GOGER SIMONE,
KÖSTNER KIM,
SCHILLING MARTIN K.,
MENGER MICHAEL D.
Publication year - 2009
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680802714127
Subject(s) - microcirculation , intravital microscopy , heme oxygenase , bilirubin , blood flow , chemistry , medicine , systemic administration , endocrinology , heme , biochemistry , biology , in vivo , microbiology and biotechnology , enzyme
Background: Metalloporphyrins (MPs) are broadly used in the studies of the role of the heme oxygenase (HO)‐1 system in different stress models. However, possible side effects of the MP administration itself have to be further investigated. Methods: Sin IV mesoporpyhrin IX (SnMP; 10 μmol/kg body weight), tin protoporpyhrin IX (SnPP; 50 μmol/kg body weight), or chromium mesoporpyhrin IX (CrMP; 40 μmol/kg body weight) were administered to Sprague‐Dawley rats (each group, n =5). The hepatic microcirculation was assessed by intravital microscopy (IVM). Blood samples were taken and the activity of HO‐1 inhibition was measured by the determination of bilirubin accumulation after bile duct ligation. Results: CrMP administration led to a decrease in mean arterial pressure. CrMP induced a marked hemolysis, a significant decrease of sinusoidal diameter and blood flow, and a marked inflammatory response. SnMP decreased sinusoidal diameters; however, this was compensated by an increase of sinusoidal red blood cell velocity. SnPP, but not SnMP, led to an increase of the number of nonperfused sinusoids. SnPP and CrMP revealed a two‐fold increase in aspartite aminotransferase values after the completion of the IVM. The administration of MPs led to a 40%–50% decrease in the levels of conjugated bilirubin therapy, indicating that they actually inhibit HO‐1 activity. Conclusions: The administration of MPs affects both the systemic macrohemodynamics and the hepatic microcirculation. As SnMP displayed the smallest number of side effects, this MP can be recommended for the studies of the HO‐1 action on the liver microcirculation.