Three thiamine analogues differently alter thiamine transport and metabolism in nervous tissue: An in vivo kinetic study using rats

G. Rindi, C. Patrini, A. Nauti, R. Bellazzi, P. Magni

Research output: Contribution to journalArticlepeer-review

Abstract

Thiamine (T) analogues pyrithiamine, oxythiamine or amprolium in amounts 10-1000 times higher than labelled T, were i.p. injected into rats together with 14C-T (30 μg; 46.25 KBq). The radioactivity associated with T and its phosphoesters in the plasma and cerebral cortex, brainstem, cerebellum, and sciatic nerve were determined at time intervals from 0.25 to 240 h from injection. The experimental data obtained were processed with a mathematical compartmental model that calculated the fractional rate constants. These are the amount of content in a given compartment that is replaced in 1 h and expressed in per hour. The results showed that all three analogues inhibited thiamine entry from plasma. Instead, oxythiamine enhanced T phosphorylation to T pyrophosphate (TPP); amprolium and oxythiamine enhanced TPP dephosphorylation to monophosphate (TMP); pyrithiamine reduced TPP dephosphorylation and TMP formation, while none of the analogues modified TMP dephosphorylation to T. In conclusion, in living rats, the action of T analogues was much more complex than could be expected from their structure and action in vitro.

Original languageEnglish
Pages (from-to)245-263
Number of pages19
JournalMetabolic Brain Disease
Volume18
Issue number4
DOIs
Publication statusPublished - Dec 2003

Keywords

  • Compartmental model
  • Kinetics in vivo
  • Nervous tissue
  • Thiamine
  • Thiamine analogues
  • Thiamine phosphoesters

ASJC Scopus subject areas

  • Clinical Neurology
  • Biochemistry
  • Neuroscience(all)

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