title: Inhibition of apoptosis prevents liver failure and improves survival rates after extensive hepatectomy in rats.
abstract: An important cause of postoperative hepatic failure is an inappropriate extensive hepatectomy (HPx). Recent data indicate that apoptosis plays a crucial role in the post-HPx remnant liver dysfunction. We advanced the hypothesis that inhibition of apoptosis prevents liver failure after HPx. It was shown that Cyclosporin A (Cys) protects against apoptosis. To investigate whether post-HPx liver failure is an apoptosis dependent phenomenon, we pretreated Sprague-Dawley rats with Cys A (10 mg/kg) immediately before 85% HPx. A group was submitted to HPx only, and control animals were sham-operated. Twenty-four hours later, half of the animals of each group were sacrificed and liver was fixed for optical observation. The remaining rats were followed-up for survival rates. Liver dysfunction at sacrifice was significantly lower in Cys treated animals as demonstrated by serum levels of total and direct bilirubin, AST and ALT (p < 0.05). In parallel, the Cys A group disclosed a lower number of apoptotic cells, and less severe liver injuries (p = 0.000). HPx rat survival was marginally ameliorated by Cys pretreatment. Our data support the hypothesis that apoptosis is a relevant mechanism of post-HPx hepatic failure.
authors.affiliation: Department of Surgery, Ankara Training and Research Hospital, Yenimahalle Branch, Ankara, Turkey. tanju_acar@yahoo.com
authors.forename: T
authors.initials: T
authors.lastname: Acar
authors.forename: K
authors.initials: K
authors.lastname: Ceyhan
authors.forename: T
authors.initials: T
authors.lastname: Colakoglu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D016572:Cyclosporine / Q000494:pharmacology*; D006498:Hepatectomy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008099:Liver / Q000473:pathology; D017093:Liver Failure / Q000097:blood / Q000517:prevention & control; D008297:Male; D011300:Preoperative Care; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin