title: Effect of tacrolimus and partial hepatectomy on transthyretin metabolism in rats.
abstract: Liver transplantation, which serves as treatment of familial amyloidotic polyneuropathy (FAP), and domino liver transplantation, which utilizes resected livers from patients with FAP for treatment of liver diseases, may induce changes in transthyretin (TTR), a pathogenic FAP-related protein. To evaluate this possibility, we performed a 70% hepatectomy or administered tacrolimus to Dark Agouti (DA) rats for 7 days and then measured changes in liver TTR mRNA levels and changes in serum TTR concentrations. After hepatectomy, TTR mRNA levels decreased by 77%; at day 3, they returned to preoperative levels. Except for slightly elevated serum TTR concentrations 12 h after operation, serum TTR levels remained unchanged. Thus, partial hepatectomy did not influence serum TTR concentrations. After tacrolimus administration, TTR mRNA declined by 56% 12 h after the experiment started; however, after day 3, a rebound phenomenon occurred until day 7. Tacrolimus may facilitate serum TTR degradation, although production of TTR in the liver also increased. This finding -- that TTR, the source of FAP-inducing amyloid, did not increase after transplantation -- may help post-transplantation treatment of patients who have FAP and other liver diseases.
authors.affiliation: Department of Pediatric Surgery and Transplantation, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Manuel E
authors.initials: ME
authors.lastname: Zeledon R
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Asonuma
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Xuguo
authors.initials: X
authors.lastname: Sun
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Junko
authors.initials: J
authors.lastname: Fujii
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Inomata
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D005786:Gene Expression Regulation; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D015233:Models, Statistical; D011228:Prealbumin / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016559:Tacrolimus / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D011228:Prealbumin; D012333:RNA, Messenger; D001219:Aspartate Aminotransferases; D016559:Tacrolimus