Cobalt-protoporphyrin induced heme oxygenase overexpression and its impact on liver regeneration

Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect from ischemia-reperfusion injury, which remains a major source of graft loss after liver transplantation. The impact of HO-1 on liver regeneration, especially in reduced-size grafts, has not yet been evaluated. Using an experimental model, we investigated HO-1 induction by CoPP treatment on postoperative recovery of ischemically injured livers following partial (70%) hepatectomy. Wistar rats underwent partial hepatectomy under temporary inflow occlusion (30 minutes). One group of animals received CoPP (5 mg/kg body weight i.p.) 24 hours prior to surgery to induce high levels of HO-1 at the time of surgery, and the second group served as nontreated controls. At postoperative days 1, 4, 7, and 10, animals were exsanguinated, and blood and liver samples were stored for enzymatic (serum AST and ALT levels) and histologic (mitotic index) analyses (n = 5 each day). Additionally, postoperative body weight and weight of the remnant liver were measured. Although serum AST and ALT levels as well as remnant liver weight were comparable between both groups, CoPP-treated animals recovered from surgery more quickly as indicated by postoperative body weight. Moreover, the number of mitotic cells was significantly increased in this group at day 1 (33 +/- 5 versus 20 +/- 5 per 2000 hepatocytes) as compared with nontreated animals. Liver regeneration of ischemically injured livers following partial hepatectomy was improved by HO-1 overexpression following preoperative CoPP administration. Thus, it is conceivable that prevention of ischemia-reperfusion injury by HO-1 overexpression also might be beneficial for reduced-size liver grafts without affecting their proliferative capacity.