Cobalt-protoporphyrin enhances heme oxygenase 1 expression and attenuates liver ischemia/reperfusion injury by inhibiting apoptosis

Li,Jing; Wu,Bin; Teng,Dahong; Sun,Xiaoye; Li,Junjie; Li,Jiang; Zhang,Guoliang; Cai,Jinzhen

doi:10.3892/mmr.2018.8384

Cobalt-protoporphyrin enhances heme oxygenase 1 expression and attenuates liver ischemia/reperfusion injury by inhibiting apoptosis

Authors:
- Jing Li
- Bin Wu
- Dahong Teng
- Xiaoye Sun
- Junjie Li
- Jiang Li
- Guoliang Zhang
- Jinzhen Cai
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Affiliations: Departments of Transplantation and Gastroenterology, Tianjin Medical University, Tianjin 300070, P.R. China, Department of Transplantation, Tianjin First Central Hospital of Tianjin Medical University, Tianjin 300192, P.R. China, Department of Gastroenterology, Tianjin First Central Hospital of Tianjin Medical University, Tianjin 300192, P.R. China
Published online on: January 5, 2018 https://doi.org/10.3892/mmr.2018.8384
Pages: 4567-4572

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Abstract

The aim of the present study was to investigate the preconditioning effect and underlying mechanisms of cobalt-protoporphyrin (CoPP) in a mouse model of liver ischemia‑reperfusion (I/R) injury. Mice were divided into five groups: Sham‑operated (control), I/R, I/R + CoPP, I/R + CoPP and zinc‑protoporphyrin (ZnPP) and I/R + ZnPP. Serum levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) were detected using commercial kits. The expression of the pro‑apoptotic protein caspase‑3 was detected by immunohistochemistry and the expression levels of the anti‑apoptotic protein B‑cell lymphoma 2 (Bcl‑2) and heme oxygenase 1 (HO‑1) were analyzed by western blotting. Sections of liver tissue were stained with hematoxylin and eosin to observe pathologic alterations. Furthermore, hepatocyte apoptosis was detected using a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. AST and ALT levels of the CoPP preconditioned group were significantly reduced compared with the IR injury group (P<0.05) and liver damage was attenuated. The expression levels of the pro‑apoptotic protein caspase3 was inhibited and those of HO‑1 and Bcl‑2 were increased in the CoPP group compared with the I/R group; the opposite results were observed in the ZnPP group. Furthermore, the percentage of apoptotic cells as detected by TUNEL was significantly decreased in the CoPP group compared with the I/R group (P<0.05); these protective effects were abrogated by ZnPP. In conclusion, the results of the present study suggested that CoPP may induce HO‑1 overexpression and produce anti‑apoptotic effects in liver I/R injury.

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