Reduction of ischemia reperfusion injury after liver resection and hepatic inflow occlusion by alpha-lipoic acid in humans.
OBJECTIVE
To evaluate the protective effects of preconditioning by alpha-lipoic acid (LA) in patients undergoing hepatic resection under inflow occlusion of the liver.


METHODS
Twenty-four patients undergoing liver resection for various reasons either received 600 mg LA or NaCl 15 min before transection performed under inflow occlusion of the liver. Blood samples and liver wedge biopsy samples were obtained after opening of the abdomen immediately after inflow occlusion of the liver, and 30 min after the end of inflow occlusion of the liver.


RESULTS
Serum levels of aspartate transferase and alanine transferase were reduced at all time points in patients who received LA in comparison to those who received NaCL. This was accompanied by reduced histomorphological features of oncosis. We observed TUNEL-positive hepatocytes in the livers of the untreated patients, especially after 30 min of ischemia. LA attenuated this increase of TUNEL-positive hepatocytes. Under preconditioning with LA, ATP content was significantly enhanced after 30 min of ischemia and after 30 min of reperfusion.


CONCLUSIONS
This is the first report on the potential for LA reducing ischemia/reperfusion injury (IRI) of the liver in humans who were undergoing liver surgery. Beside its simple and rapid application, side effects did not occur. LA might therefore represent a new strategy against hepatic IRI in humans.
Dünschede
Fritz
F
Department of General and Abdominal Surgery, University Hospital Mainz, Germany. duenschede@ach.klinik.uni-mainz.de
Erbes
Kirsten
K
Kircher
Achim
A
Westermann
Stefanie
S
Seifert
Joachim
J
Schad
Arno
A
Oliver
Kempski
K
Kiemer
Alexandra-K
AK
Theodor
Junginger
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D002802:Cholinesterases / Q000097:blood; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007773:Lactates / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000601:surgery*; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D015427:Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control*; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D007773:Lactates; D008063:Thioctic Acid; D000255:Adenosine Triphosphate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002802:Cholinesterases