An insight into the protection of rat liver against ischemia/reperfusion injury by 2-selenium-bridged beta-cyclodextrin

作者:Lin, Ting-ting; Wang, Bing-mei; Li, Xin-yang; Pan, Yu; Wang, Wei; Mu, Ying; Liu, Jun-qiu; Shen, Jia-cong; Luo, Gui-min*
来源:Hepatology Research, 2009, 39(11): 1125-1136.
DOI:10.1111/j.1872-034X.2009.00545.x

摘要

Aim: The reperfusion following liver ischemia results in the damage and apoptosis of hepatocytes. The aim of this study was to investigate the possible effects and mechanism of a new synthesized glutathione peroxidase (GPX) mimic, 2-selenium-bridged beta-cyclodextrin (2-SeCD), on rat liver ischemia-reperfusion (I/R) injury. Methods: Male Wistar rats (n = 32) were randomly divided into four groups: I. sham-operated group, II. I/R group, III. I/R +2-SeCD group, IV. I/R + Ebselen group. Hepatic I/R was administered by 90 min of ischemia and 12 h of reperfusion. Liver tissues were collected at the end of reperfusion period for measurement of various biochemical parameters. Results: The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) activity and tissue malondialdehyde, myeloperoxidase levels were increased in I/R group, while the increase was significantly reduced by 2-SeCD treatment. The glutathione level, depressed by I/R, was elevated back to normal levels by treatment with 2-SeCD. Severe hepatic damage were observed by light and transmission electron microscopy whilst pretreatment with 2-SeCD resulted in tissue and cellular preservation. Furthermore, 2-SeCD reduced cytochrome c release from mitochondria and subsequent DNA fragmentation by regulating Bcl-2/Bax expression ratio. Results suggested that 2-SeCD was more effective than ebselen in the reversal of the alteration in tissue structural and biochemical parameters caused by I/R injury. Conclusion: 2-selenium-bridged beta-cyclodextrin playes an important role in the protection of liver against I/R injury and this treatment may be a novel pharmacological agent for liver surgery.