title: Dopamine impairs functional integrity of rat hepatocytes through nuclear factor kappa B activity modulation: An in vivo, ex vivo, and in vitro study.
abstract: Dopamine (DA) is commonly used to maintain the hemodynamic stability of brain-dead donors despite its controversial effects on organ functions. This study aimed at examining the hemodynamic effect of DA in a rat brain-dead model in vivo, alteration of hepatocyte integrity in liver grafts after ex vivo preservation, and changes in cultured clone-9 hepatocytes including cellular viability, cell cycle, apoptotic regulators, and lipopolysaccharide (LPS)-stimulated nuclear factor kappa B (NF-κB) signaling machinery. Although in vivo findings demonstrated enhanced portal venous blood flow and hepatic microcirculatory perfusion after DA infusion, no apparent advantage was noted in preserving hepatocyte integrity ex vivo. In vitro, prolonged exposure to high-dose DA reduced proliferation and induced G1 growth arrest of clone-9 hepatocytes with concomitant decreases in B cell lymphoma 2 (BCL2)/B cell lymphoma 2-associated X protein (BAX) and heat shock protein 70/BAX protein ratios and intracellular NF-κB p65. Moreover, DA pretreatment suppressed LPS-elicited inhibitor of κBα phosphorylation and subsequent NF-κB nuclear translocation, suggesting that DA may down-regulate NF-κB signaling, thereby reducing expression of antiapoptotic regulators, such as BCL2. In conclusion, despite augmentation of hepatic perfusion, DA infusion failed to preserve hepatocyte integrity both in vivo and ex vivo. In vitro findings demonstrated that high-dose DA may hamper the function of NF-κB signaling machinery and eventually undermine functional integrity of hepatocytes in liver grafts.
authors.affiliation: Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan.|Department of Emergency Medicine, E-Da Hospital, Kaohsiung, Taiwan.|The School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.affiliation: Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.affiliation: Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Department of Food Science, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Wu
authors.affiliation: Department of Food Science, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors.forename: Kun-Cho
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Shian
authors.initials: MS
authors.lastname: Tsai
authors.affiliation: Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Po-Han
authors.initials: PH
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008102:Liver Circulation; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009926:Organ Preservation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D002316:Cardiotonic Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D004298:Dopamine