4.7 Article

Protective Effect of N-Acetylserotonin against Acute Hepatic Ischemia-Reperfusion Injury in Mice

Journal

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 14, Issue 9, Pages 17680-17693

Publisher

MDPI
DOI: 10.3390/ijms140917680

Keywords

N-acetylserotonin; newborn mouse; hepatic ischemia-reperfusion injury; apoptosis

Funding

  1. Shandong Province Natural Science Foundation [ZR2010HM006, ZR2010HM065, ZR2010HM087]
  2. Shandong Province Higher Educational Science and Technology Program [J11LF14]
  3. Shandong Province Medicine and Health Science Technology Program [2013WSB27011]
  4. Bill & Melinda Gates Foundation [BMGF: 01075000191]
  5. Muscular Dystrophy Association [254530]
  6. Shandong Province Taishan scholar project

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The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD) was evaluated by enzyme-linked immunosorbent assay (ELISA). The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury.

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