Inhibition of apoptosis prevents liver failure and improves survival rates after extensive hepatectomy in rats.
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.
Acar
T
T
Department of Surgery, Ankara Training and Research Hospital, Yenimahalle Branch, Ankara, Turkey. tanju_acar@yahoo.com
Ceyhan
K
K
Colakoglu
T
T
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
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin