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.