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05). Additionally, fibrotic mice showed a second, unexpected peak in ALT levels in the late recovery phase between days 4 and 6, peaking on day 5 (3542 �� 246 IU/L versus 93 �� 65 IU/L in nonfibrotic controls, P 0.0001) ( Figure?2A). Accordingly, serum AST, alkaline phosphatase, and total bilirubin increased in normal mice only transiently at 1 day, but peaked in fibrotic mice at a late day 5 time point and remained elevated at day 10 ( Supplemental Table S1). Careful histological examination revealed that see more at postoperative day 5, 71% of fibrotic mice showed focal eosinophilic lesions in the periportal area consisting of large numbers of dead hepatocytes not found in the fibrotic livers at earlier (days 1 to 3) or later (days 10 to 14) time points and at no point in regenerating nonfibrotic livers ( Figure?2C). TUNEL staining revealed a high rate of cell apoptosis, predominantly localizing to areas of focal hepatocyte death, suggesting that hepatocyte cell death occurred via apoptosis ( Figure?2C). Thalidomide In fibrotic livers before PHx, TUNEL+ cells were observed in fewer numbers and localized within portal tracts and fibrotic septa ( Figure?2D), whereas normal livers were virtually TUNEL negative before and 5 days after hepatectomy. No cholangiocyte death could be detected histologically (neither in bile ducts nor pseudo ducts of normal or fibrotic mice, not shown). After 70% PHx in nonfibrotic livers, organ volume and function was quickly restored via robust replication of almost all mature hepatocytes, as assessed by immunostaining of liver sections for the nuclear proliferation marker Ki-67. In normal livers before surgery, hepatocytes were quiescent. After PHx, hepatocytes began to proliferate, peaking at day 2 postsurgery (79% Ki-67+ hepatocytes) (Figure?2, B and E). As expected in fibrotic livers, the baseline hepatocyte proliferation was elevated before PHx due to ongoing chronic liver injury and hepatocyte regeneration. However, Ki-67 staining in livers of fibrotic mice was severely blunted with only http://www.selleckchem.com/products/Abiraterone.html 1.8% and 10.5% of hepatocytes proliferating on days 2 and 3, respectively, compared with 7.3% and 79.1% in normal mice (P