title: Effect of albumin on transthyretin and amyloidogenic transthyretin Val30Met disposition and tissue deposition in familial amyloidotic polyneuropathy.
abstract: OBJECTIVE
  Transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) is characterized by the systemic accumulation of amyloid fibrils caused by amyloidogenic. Our previous studies demonstrated that albumin played a role in the inhibition of TTR amyloid-formation. The aim of this study was to evaluate the effect of albumin on TTR disposition and tissue deposition in vivo.
  
  
  METHODS
  For pharmacokinetic studies, recombinant wild-type TTR (rTTR) and recombinant amyloidogenic TTR Val30Met (rATTR V30M) were labeled with iodine and administered to Sprague-Dawley rats and analbuminemia rats (NAR: Nagase Analbuminemia Rats). The deposition of ATTR V30M was also analyzed by immunohistochemistry in the transgenic (Tg) rats possessing a human ATTR V30M gene (ATTR V30M Tg rats) and NAR possessing a human ATTR V30M gene (ATTR V30M Tg NAR).
  
  
  RESULTS
  The presence of albumin had no effect on the tissue distribution of either rTTR or rATTR V30M. However, more ATTR V30M was deposited in the hearts, stomachs and small intestines of ATTR V30M Tg NAR rats, compared to ATTR V30M Tg rats.
  
  
  CONCLUSIONS
  Although the disposition of TTR and ATTR V30M was unaffected by the presence of albumin, the deposition of ATTR V30M in some organs was apparently increased in the absence of albumin compared to the presence of albumin. These results show that albumin would contribute to suppressing the tissue deposition of TTR in pathogenesis of FAP, but does not affect the disposition of TTR.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Taguchi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.forename: Tomoe
authors.initials: T
authors.lastname: Kugimiya-Taguchi
authors.forename: Saori
authors.initials: S
authors.lastname: Nagao
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Mineyuki
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
mesh_terms: D000418:Albumins / Q000235:genetics / Q000378:metabolism*; D028227:Amyloid Neuropathies, Familial / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D006801:Humans; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000418:Albumins; D011228:Prealbumin; D011994:Recombinant Proteins
keywords: % of ID; % of injection of dose; (125)I; ATTR; AUC; Albumin; CL; FAP; Familial amyloidotic polyneuropathy; NAR; Nagase Analbuminemia Rats; TTR; Tg; Transthyretin; V(1); V(2); V(dss); amyloidogenic transthyretin; area under the concentration-time curve; clearance; distribution volume; distribution volume of central compartment; distribution volume of peripheral compartment; distribution-phase half-life; elimination-phase half-life; familial amyloidotic polyneuropathy; iodine; t(1/2 α); t(1/2 β); transgenic; transthyretin