title: Amiodarone as an autophagy promoter reduces liver injury and enhances liver regeneration and survival in mice after partial hepatectomy.
abstract: The deregulation of autophagy is involved in liver regeneration. Here, we investigated the role of autophagy in the regulation of liver regeneration after partial hepatectomy (PHx) and the development of pharmacological interventions for improved liver regeneration after PHx. We show that autophagy was activated in the early stages of liver regeneration following 70% PHx in vivo. Moreover, amiodarone was associated with a significant enhancement of autophagy, liver growth, and hepatocyte proliferation, along with reduced liver injury and the termination of liver regeneration due to decreased transforming growth factor-β1 expression after 70% PHx. The promotion of autophagy appeared to selectively increase the removal of damaged mitochondria. We also found that Atg7 knockdown or pretreatment with chloroquine aggravated the liver injury associated with 70% PHx and reduced liver growth and hepatocyte proliferation. Finally, amiodarone improved liver regeneration, survival, and liver injury after 90% PHx. In conclusion, our results indicate that autophagy plays an important role in mouse liver regeneration and that modulating autophagy with amiodarone may be an effective method of improving liver regeneration, increasing survival, and ameliorating liver injury following PHx.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung.|Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung.|Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung.|School of Medicine, College of Medicine, I-Shou University, Kaohsiung.
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Lin
authors.affiliation: School of Medicine, College of Medicine, I-Shou University, Kaohsiung.|Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung.
authors.forename: Yaw-Sen
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung.
authors.forename: Chih-Che
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung.|Department of Biological Science &Technology, I-Shou University, Kaohsiung.
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung.|School of Medicine, College of Medicine, I-Shou University, Kaohsiung.
authors.forename: Gin-Ho
authors.initials: GH
authors.lastname: Lo
authors.affiliation: School of Medicine, College of Medicine, I-Shou University, Kaohsiung.|Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung.
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung.
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung.|Faculty of Medicine, College of Medicine, and Center for Infectious Disease and Cancer Research, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung.
authors.forename: Jee-Fu
authors.initials: JF
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung.
authors.forename: Wang-Long
authors.initials: WL
authors.lastname: Chung
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung.|Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung.|Faculty of Medicine, College of Medicine, and Center for Infectious Disease and Cancer Research, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung.|Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D000071193:Autophagy-Related Protein 7; D002738:Chloroquine / Q000494:pharmacology; D004195:Disease Models, Animal; D006498:Hepatectomy; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism / Q000401:mortality; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C502661:Atg7 protein, mouse; D015850:Interleukin-6; D016209:Interleukin-8; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D002738:Chloroquine; D058570:TOR Serine-Threonine Kinases; D000071193:Autophagy-Related Protein 7; D000638:Amiodarone