Propofol displays no protective effect against hypoxia/reoxygenation injury in rat liver slices.
Using precision-cut liver slices (20-25 mg wet weight) from male Wistar rats, we examined whether clinically relevant propofol concentrations have hepatoprotective or -toxic effects during hypoxia/reoxygenation. Slices were preincubated for 2 h in sealed roller vials (three slices per vial) containing Waymouth's medium (37 degrees C; 95% oxygen/5% CO(2)). Then, propofol or Intralipid was added to create four different groups (control, Intralipid, small-concentration propofol [0.5-1.5 micro g/mL], and large-concentration propofol [2.0-6.0 micro g/mL]). Thereafter, each group was incubated for 4 h under 95% oxygen/5% CO(2) (no hypoxia) or for 2 h under 100% nitrogen plus 2 h under 95% oxygen/5% CO(2) (hypoxia/reoxygenation). Slice viability and hypoxia/reoxygenation injury were assessed at 2, 3, and 4 h after incubation began by using the slice intracellular K(+) concentration, energy status (adenosine triphosphate content, total adenine nucleotides content, and energy charge), and liver enzyme leakage (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase). Propofol and Intralipid caused a significant delay in energy charge recovery in comparison with the control. There were no significant differences between the propofol groups and the other two groups in intracellular K(+) content or liver enzyme leakage. Propofol had no hepatotoxic effect under no-hypoxia conditions in rat liver slices, nor did it have a protective effect against hypoxia/reoxygenation-induced hepatic injury.


CONCLUSIONS
Propofol had no hepatotoxic effect under no-hypoxia conditions in rat liver slices, nor did it have a protective effect against hypoxia/reoxygenation-induced hepatic injury.
Shimono
Hiroo
H
Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, Kagoshima, Japan.
Goromaru
Teruko
T
Kadota
Yoshitami
Y
Tsurumaru
Takeshi
T
Kanmura
Yuichi
Y
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015687:Cell Hypoxia; D003470:Culture Media; D004734:Energy Metabolism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption; D011188:Potassium / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
D000227:Adenine Nucleotides; D018686:Anesthetics, Intravenous; D003470:Culture Media; D020011:Protective Agents; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D011188:Potassium; D015742:Propofol