Inhibition of hemoxygenase-1 improves survival after liver resection in jaundiced rats.

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. 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. 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. 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.