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.
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Rindi, G., Patrini, C., Nauti, A. et al. Three Thiamine Analogues Differently Alter Thiamine Transport and Metabolism in Nervous Tissue: An In Vivo Kinetic Study Using Rats. Metab Brain Dis 18, 245–263 (2003). https://doi.org/10.1023/B:MEBR.0000020187.98238.58
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DOI: https://doi.org/10.1023/B:MEBR.0000020187.98238.58