Hepatocellular injury of nonischemic liver tissue after selective clamping in rats--protective action by pharmacological pretreatment with lipoic acid.
OBJECTIVE
The aim of the study was to characterize the hepatic injury (HI) of the nonischemic liver lobe after selective portal triad clamping and investigate the influence of pharmacological pretreatment with alpha-lipoic acid (LA).


METHODS
Brown-Norway rats received 500 micromol LA injected via the inferior vena cava 15 min prior to the induction of 90 min of selective ischemia. Another group of rats received vehicle prior to ischemia. Both groups were compared with sham-operated animals.


RESULTS
Lipid peroxidation (LPO) was increased in the ischemic as well as in the nonischemic liver tissue (NIL) in the untreated group. Levels of adenosine triphosphate and reduced glutathione content of the nonischemic liver lobe were decreased in the untreated group 1 h after reperfusion. Activity of caspases 3 and 8 was not detectable, whereas expression of the Bax protein was demonstrated in the NIL. We observed areas of necrotic hepatocytes and large gaps of sinusoids in the NIL of the untreated rats. LA attenuated LPO as well as Bax expression in the NIL. Moreover adenosine triphosphate and glutathione content of the NIL was increased 1 h after reperfusion by LA. LA pretreatment reduced release of alpha-glutathione-s-transferase in plasma. Histology of the nonischemic liver lobe did not markedly differ from sham-operated animals after LA pretreatment.


CONCLUSIONS
HI of the NIL seems to be mediated by LPO and proapoptotic proteins such as Bax. Besides its described potential to reduce ischemia/reperfusion injury of the ischemic lobe, LA attenuates HI of the nonischemic tissue after selective portal triad clamping.
Duenschede
F
F
Department of General and Abdominal Surgery, University Hospital Mainz, Mainz, Germany. duenschede@ach.klinik.uni-mainz.de
Westermann
S
S
Miesner
I
I
Albrecht-Schöck
S
S
Kneist
W
W
Korenkov
M
M
Schad
A
A
Dutkowski
Ph
P
Kiemer
A K
AK
Junginger
T
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D003250:Constriction; D004195:Disease Models, Animal; D007511:Ischemia / Q000150:complications*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply / Q000187:drug effects*; D008107:Liver Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D008063:Thioctic Acid