Metalloporphyrins, used for HO-1 inhibition, themselves affect hepatic microcirculation, liver function, and

Stefan Scheingraber1, Sven Messner, Susanne Matt

  • 1Department of General, Visceral, Vascular, and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany. stefan.scheingraber@diekliniken.de

Microcirculation (New York, N.Y. : 1994)
|March 21, 2009
PubMed
Abstract

Insights

Metalloporphyrins (MPs) impact liver microcirculation and hemodynamics. Tin mesoporphyrin IX (SnMP) showed fewer side effects and is recommended for heme oxygenase-1 studies.

Area of Science:

  • Pharmacology
  • Hepatology
  • Physiology

Background:

  • Metalloporphyrins (MPs) are widely used to study heme oxygenase-1 (HO-1) in stress models.
  • Potential side effects of MP administration require further investigation.

Purpose of the Study:

  • To investigate the systemic and hepatic microcirculatory effects of different metalloporphyrins (MPs).
  • To identify the metalloporphyrin with the most favorable side effect profile for heme oxygenase-1 research.

Main Methods:

  • Administration of tin mesoporphyrin IX (SnMP), tin protoporphyrin IX (SnPP), and chromium mesoporphyrin IX (CrMP) to rats.
  • Assessment of hepatic microcirculation using intravital microscopy (IVM).
  • Measurement of HO-1 inhibition via bilirubin accumulation after bile duct ligation.

Main Results:

  • CrMP caused hemolysis, decreased blood pressure, sinusoidal diameter, and blood flow, alongside inflammation.
  • SnMP reduced sinusoidal diameter but increased red blood cell velocity; SnPP increased nonperfused sinusoids.
  • SnMP and CrMP elevated aspartate aminotransferase; all MPs inhibited HO-1, indicated by reduced bilirubin levels.

Conclusions:

  • Metalloporphyrin administration significantly impacts systemic hemodynamics and liver microcirculation.
  • Tin mesoporphyrin IX (SnMP) exhibited the fewest adverse effects among the tested MPs.
  • SnMP is recommended for future studies investigating the role of heme oxygenase-1 in liver microcirculation.

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