Eicosanoid-mediated increase in glucose and lactate output as well as decrease and redistribution of flow by...

Area of Science:

• Biochemistry
• Physiology
• Immunology

Background:

• The complement system plays a crucial role in immune responses.
• Understanding complement's impact on liver function is vital for metabolic and hemodynamic research.

Purpose of the Study:

• To investigate the effects of complement-activated rat serum on isolated perfused rat liver metabolism and hemodynamics.
• To identify the specific mediators involved in these complement-induced alterations.

Main Methods:

• Isolated perfused rat liver model.
• Incubation of rat serum with zymosan to activate the complement system.
• Measurement of glucose and lactate output, and hepatic blood flow.
• Pharmacological inhibition using cyclooxygenase and lipoxygenase pathway inhibitors, and thromboxane/leukotriene antagonists.

Main Results:

• Complement-activated serum significantly increased glucose and lactate output and altered hepatic blood flow compared to control serum.
• These metabolic and hemodynamic changes were dose-dependent and largely abolished by heat inactivation of the serum.
• Effects were significantly inhibited by indomethacin (cyclooxygenase inhibitor) and BM 13505 (thromboxane antagonist), but less so by nordihydroguaiaretic acid and CGP 35949 B.
• Complement activation led to increased thromboxane B2 and prostaglandin F2 alpha in the hepatic vein.

Conclusions:

• Activated complement in rat serum influences liver metabolism and hemodynamics.
• This influence is mediated by the release of thromboxane and prostaglandins from non-parenchymal liver cells.
• These mediators, in turn, affect parenchymal liver cells, highlighting a complex intra-liver signaling pathway.