Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats

被引:15
作者
Sheen, Jiunn-Ming [1 ,2 ,3 ]
Chen, Yu-Chieh [1 ,2 ]
Hsu, Mei-Hsin [1 ,2 ]
Tain, You-Lin [1 ,2 ]
Huang, Ying-Hsien [1 ,2 ]
Tiao, Mao-Meng [1 ,2 ]
Li, Shih-Wen [1 ,2 ]
Huang, Li-Tung [1 ,2 ]
机构
[1] Kaohsiung Chang Gung Mem Hosp, Dept Pediat, 123 Ta Pei Rd, Kaohsiung 833, Taiwan
[2] Chang Gung Univ, Coll Med, 123 Ta Pei Rd, Kaohsiung 833, Taiwan
[3] Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Taoyuan 333, Taiwan
关键词
bile duct ligation; melatonin; apoptosis; endoplasmic reticulum; mitochondria; OXIDATIVE STRESS; ASYMMETRIC DIMETHYLARGININE; HEPATOCYTE APOPTOSIS; NADPH OXIDASE; PLASMA-LEVELS; CELL-DEATH; DAMAGE; EXPRESSION; RECEPTORS; BRAIN;
D O I
10.3390/ijms17081365
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bile duct ligation (BDL)-treated rats display cholestasis and liver damages. The potential protective activity of melatonin in young BDL rats in terms of apoptosis, mitochondrial function, and endoplasmic reticulum (ER) homeostasis has not yet been evaluated. Three groups of young male Sprague-Dawley rats were used: one group received laparotomy (Sham), a second group received BDL for two weeks (BDL), and a third group received BDL and intraperitoneal melatonin (100 mg/day) for two weeks (BDL + M). BDL group rats showed liver apoptosis, increased pro-inflamamtory mediators, caspases alterations, anti-apoptotic factors changes, and dysfunction of ER homeostasis. Melatonin effectively reversed apoptosis, mainly through intrinsic pathway and reversed ER stress. In addition, in vitro study showed melatonin exerted its effect mainly through the melatonin 2 receptor (MT2) in HepG2 cells. In conclusion, BDL in young rats caused liver apoptosis. Melatonin rescued the apoptotic changes via the intrinsic pathway, and possibly through the MT2 receptor. Melatonin also reversed ER stress induced by BDL.
引用
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页数:15
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