Metalloporphyrins, used for HO-1 inhibition, themselves affect hepatic microcirculation, liver function, and hepatocellular integrity.
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 micromol/kg body weight), tin protoporpyhrin IX (SnPP; 50 micromol/kg body weight), or chromium mesoporpyhrin IX (CrMP; 40 micromol/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.
Scheingraber
Stefan
S
Department of General, Visceral, Vascular, and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany. stefan.scheingraber@diekliniken.de
Messner
Sven
S
Matt
Susanne
S
Abel
Kathrin
K
Goger
Simone
S
Kötner
Kim
K
Schilling
Martin K
MK
Menger
Michael D
MD
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors*; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D008102:Liver Circulation / Q000187:drug effects*; D008665:Metalloporphyrins / Q000494:pharmacology*; D008833:Microcirculation / Q000187:drug effects; D018715:Microscopy, Video; D051381:Rats; D017207:Rats, Sprague-Dawley; D012107:Research Design
D008665:Metalloporphyrins; D051547:Heme Oxygenase-1