title: 17β-estradiol attenuates reduced-size hepatic ischemia/reperfusion injury by inhibition apoptosis via mitochondrial pathway in rats.
abstract: The aim of this study was to investigate the effect of 17β-estradiol (E2) on hepatocyte apoptosis after reduced-size hepatic ischemia/reperfusion (I/R) injury and its mechanism. A rat model of reduced-size hepatic I/R injury was established. Sprague-Dawley rats were randomly allocated into sham, I/R, and E2 + I/R group. 17β-Estradiol (4 mg/kg) or the vehicle was administered i.p. 1 h before ischemia and immediately after operation. For each group, 10 rats were used to investigate the survival during a week after reperfusion. Blood samples and liver tissues were obtained in the remaining animals after 3, 6, 12, and 24 h of reperfusion to assess serum aspartate aminotransferase and alanine aminotransferase levels, liver tissue malondialdehyde concentration, superoxide dismutase activity, and histopathologic changes. Apoptosis ratio; expression of cytochrome c, Bcl-2, and Bax proteins; and enzymatic activities of caspase 9 and caspase 3 were performed in the samples at 12 h after reperfusion. The serum aspartate aminotransferase and alanine aminotransferase levels and tissue malondialdehyde concentration were increased in the I/R group, whereas the increase was significantly reduced by E2. The superoxide dismutase activity, depressed by I/R injury, was elevated back to normal levels by treatment with E2. Severe hepatic damage was observed by light microscopy in the I/R group, whereas administration of E2 resulted in tissue and cellular preservation. Furthermore, E2 inhibited hepatocellular apoptosis by upregulating the ratio of Bcl-2 and Bax expression, reduced cytosolic cytochrome c level, and decreased caspase 9 and caspase 3 activities. The 7-day survival rate was significantly higher in the E2 + I/R group than in the I/R group. These results indicated that E2 protects liver tissues from reduced-size hepatic I/R injury by suppressing mitochondrial apoptotic pathways.
authors.affiliation: Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Fu Sheng
authors.initials: FS
authors.lastname: Lin
authors.forename: Shi Qiang
authors.initials: SQ
authors.lastname: Shen
authors.forename: Zu Bing
authors.initials: ZB
authors.lastname: Chen
authors.forename: Rui Chen
authors.initials: RC
authors.lastname: Yan
mesh_terms: D000818:Animals; D017209:Apoptosis; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors; D000637:Transaminases / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D051028:bcl-2-Associated X Protein; D004958:Estradiol; D008315:Malondialdehyde; D045304:Cytochromes c; D000637:Transaminases