Protection by glycyrrhizin against warm ischemia-reperfusion-induced cellular injury and derangement of the microcirculatory blood flow in the rat liver.

Abstract

BACKGROUND/AIM:

The mechanism by which ischemia-reperfusion (I/R)-induced derangement of the hepatic microcirculation leads to tissue injury is not fully understood. We postulated that alterations to the hepatic microcirculation, including hemodynamic derangement and increased leukocyte-endothelium interaction, play a role, and that glycyrrhizin exerts its hepatoprotective effects, in part, by reducing these microcirculatory changes.

MATERIALS AND METHODS:

Wistar rats were subjected to 30-60 minutes segmental hepatic ischemia, followed by 120 minutes of reperfusion. Glycyrrhizin was administered prior to ischemia. Using intravital fluorescence microscopy, the administration of fluorescein isothiocyanate-conjugated erythrocytes allowed the measurement of erythrocyte-velocity (RBC(vel)), lobular, and sinusoidal perfusion. Bleb formation was observed by electron microscopy. Blood and tissue were taken for the assessment of liver injury.

RESULTS:

Glycyrrhizin reduced I/R-induced liver injury (histology, liver enzymes) and reduced hepatocyte apoptosis (TUNEL, caspase-3 activity). Glycyrrhizin inhibited hepatocyte bleb formation and reversed the I/R-induced reductions in lobular perfusion and RBC(vel). Leukocyte rolling and adherence in postsinusoidal venules and neutrophil infiltration were reduced by glycyrrhizin. I/R-induced elevation in HMGB1 was prevented by glycyrrhizin.

CONCLUSIONS:

Early bleb formation with deranged microcirculatory flow and leukocyte-endothelium interaction would appear to contribute to I/R-induced hepatocellular injury. Glycyrrhizin exerts its hepatoprotective effect by preventing these changes, in addition to a direct cellular effect.

• Authors: Ayako Mabuchi, Kenjiro Wake, Muhamad Marlini, Hitomi Watanabe, Antony M Wheatley
• Journal: Microcirculation (New York, N.Y. : 1994) (Microcirculation) Vol. 16 Issue 4 Pg. 364-76 (May 2009) ISSN: 1549-8719 [Electronic] United States
• PMID: 19308793 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Protective Agents
• Glycyrrhizic Acid

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Apoptosis
• Blood Flow Velocity (drug effects)
• Cell Adhesion
• Glycyrrhizic Acid (pharmacology)
• Hemodynamics (drug effects)
• Leukocyte Rolling
• Liver Circulation (drug effects)
• Microcirculation
• Microscopy, Video
• Neutrophil Infiltration
• Protective Agents (pharmacology)
• Rats
• Rats, Wistar
• Reperfusion Injury (prevention & control)