Abstract
The effects of chronic ethanol administration on different steps of the metabolism of thiamine (T), thiamine mono- (TMP) and thiamine pyrophosphate (TPP) in the cerebellum, brainstem, cerebral cortex and sciatic nerve were evaluated in vivo. The radioactivity of T and its phosphoesters was determined in plasma and in the selected nervous structures under steady-state conditions and at fixed time intervals (0.5–192 h) after an i.p. injection of [ 14C]T (30 μg: 1.25 μCi) to rats chronically (35 days) ethanol-treated (daily dose of 4.7 g· kg −1 b.wt. by gastric gavage) and pair-fed controls similarly treated with a sucrose solution isoenergetic with ethanol. All rats were given a nutritionally adequate diet supplying an excess of thiamine, which produced a virtually steady content of thiamine compounds in the tissues. By using a compartmental mathematical model, fractional rate constants, turnover rates and turnover times were calculated. Ethanol caused a reduction of the rate of thiamine compound enzymatic transformations (T phosphorylation to TPP, TPP dephosphorylation to TMP and TMP to T), and a facilitation of the regional uptake of T and TMP, associated to a less relevant influence on their release. Isoenergetic sucrose prevailingly caused an increased rate of thiamine metabolic steps (except phosphorylation in the brainstem and cerebral cortex), with negligible modifications of T and TMP uptake and release. Thus the changes induced by ethanol were virtually opposite to those caused by sucrose.
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