title: Cobalt protoporphyrin protects the liver against apoptosis in rats of brain death.
abstract: Brain death (BD) leads to a marked increase in apoptosis, which influences the viability of donor organs. Induction of heme oxygenase 1 (HO-1) has been shown to exert beneficial effects in different liver injury models. Therefore, we examined the effect of pretreating rats with cobalt protoporphyrin (CoPP), an HO-1 inducer, on apoptosis in liver during BD and elucidated the mechanisms involved. First, rats were killed at 0, 1, 2, 4 and 6 h after BD induction to examine the expression of hepatic HO-1. Second, rats were randomly divided into four groups (n=6): (S group) rats undergoing sham operation, (CS group) rats pretreated with CoPP for 24 h before the sham operation, (B group) rats undergoing BD for 6 h, (CB group) rats pretreated with CoPP for 24 h before BD induction. The expression levels of hepatic HO-1 mRNA and protein in rats increased at 0, 1, 2, 4 and 6h after BD induction, compared with sham operated rats. In the CB group compared with the B group, the increased hepatic expression of HO-1 correlated with a significant decrease in serum ALT/AST levels, fewer apoptotic cells in liver, increased hepatic expression of Mcl-1 and Bcl-2, and decreased hepatic expression of Bax, cytosolic cytochrome c and cleaved caspase-3. CoPP inhibits apoptosis in liver of BD rats in part via modulating the mitochondrial apoptosis pathway. HO-1 may serve as a potential target for improving the quality of organs from BD donors.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Liver Transplantation Center of Henan Province, Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Jianshe East Road No. 1, Zhengzhou City, Henan 450052, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Liver Transplantation Center of Henan Province, Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Jianshe East Road No. 1, Zhengzhou City, Henan 450052, China. Electronic address: zhangshuijun@hotmail.com.
authors.forename: Shuijun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Liver Transplantation Center of Henan Province, Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Jianshe East Road No. 1, Zhengzhou City, Henan 450052, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Liver Transplantation Center of Henan Province, Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Jianshe East Road No. 1, Zhengzhou City, Henan 450052, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Liver Transplantation Center of Henan Province, Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Jianshe East Road No. 1, Zhengzhou City, Henan 450052, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Liver Transplantation Center of Henan Province, Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Jianshe East Road No. 1, Zhengzhou City, Henan 450052, China.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Liver Transplantation Center of Henan Province, Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Jianshe East Road No. 1, Zhengzhou City, Henan 450052, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001926:Brain Death; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020858:Tissue and Organ Harvesting; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; C579093:Mcl1 protein, rat; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D011524:Protoporphyrins; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; C007095:cobaltiprotoporphyrin; D045304:Cytochromes c; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3