Inhibition of hemoxygenase-1 improves survival after liver resection in jaundiced rats.
BACKGROUND
The role of hemoxygenase (HO)-1 after partial liver resection (PLR) in jaundiced animals has yet to be defined. We therefore investigated: (1) the acute effects of bile duct ligation (BDL) on bilirubin accumulation and hepatocellular integrity after PLR; (2) how BDL and PLR affect HO-1 protein expression; (3) how functional HO-1 blockade affects survival and liver regeneration after BDL and PLR.


METHODS
Male Sprague-Dawley rats were subjected to BDL or a sham operation. After 3 days, a 70% hepatectomy was performed. In a second set of experiments, BDL animals received either Sn(IV) mesoporphyrin IX dichloride (SnMP) for HO-1 blockade or a vehicle. Three days later, PLR was performed and survival of the animals was observed for 7 days.


RESULTS
PLR, BDL and both together cause a hepatocellular injury and HO-1 expression. Inhibition of HO-1 with SnMP in jaundiced rats that underwent PLR was associated with improved survival, attenuated postoperative weight loss and better liver synthesis.


CONCLUSIONS
The present findings add further evidence that the protective properties of increased HO-1 expression largely depend on the model used, and that HO-1 overexpression in the model of liver resection during acute cholestasis may also be detrimental.
Scheingraber
S
S
Department of General, Visceral, Vascular and Pediatric Surgery University of Saarland, Homburg, Germany. stefan.scheingraber@diekliniken.de
Bauer
M
M
Bauer
I
I
Bardens
D
D
Abel
K
K
Horn
A-K
AK
Schilling
M K
MK
Wolff
M
M
D000818:Animals; D001652:Bile Ducts; D001663:Bilirubin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006498:Hepatectomy; D041781:Jaundice, Obstructive / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery*; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008115:Liver Regeneration; D008297:Male; D008652:Mesoporphyrins / Q000627:therapeutic use; D009947:Organotin Compounds / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D008652:Mesoporphyrins; D009947:Organotin Compounds; C031468:mesoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D001663:Bilirubin