Anorexia and antagonism of thiamin utilization in poultry treated with furazolidone.
Furazolidone (0.4% w/w in the feed, 10 days) reduced the feed intake and growth in 9 week old chickens, and increased the amount of 5-hydroxytryptamine (5-HT) in the brain. The drug also increased the stimulation of transketolase activity by thiamine pyrophosphate (TPP) in lysed blood cells (TPP effect), and the concentrations of pyruvate and lactate in the blood. Experiments with pair-fed birds showed that the reduction in feed intake in furazolidone-treated chickens could account for the reduced growth. The drug also produced anorexia in ducklings and turkey poults. In chickens, the anorectic action of furazolidone was unaffected by methergoline (1 mg/kg, twice daily, I.M), and in ducklings furazolidone did not consistently produce anorexia, although it always inhibited monoamine oxidase (MAO) activity in the brain. These observations suggest that the anorectic action of the drug was not tryptaminergic in nature. The increase in the TPP effect found in preparations from furazolidone-treated chickens was absent in preparations from pair-fed birds on unmedicated feed. Thus the TPP effect could be used as an indicator of the effect of the drug on the thiamine status of chickens. However, the increase in the concentrations of pyruvate and lactate in blood was found both in furazolidone-treated birds and pair-fed birds on unmedicated feed, showing that they were attributable to the reduction in feed intake. The TPP effect in furazolidone-treated chickens, 14-49 +/- 2.33% (n = 10), was sufficient to suggest a mild deficiency of thiamin pyrophosphate. Thiamin, given at a dosage above the requirement of the vitamin for chickens, did not reduce the anorexia or the TPP effect of furazolidone-treated birds, although it stimulated the feed intake and growth of birds on unmedicated feed. It is proposed that furazolidone  antagonized the utilization of thiamin, perhaps by inhibiting its phosphorylation. Following the withdrawal of furazolidone, the TPP effect returned to the control value and the rate of growth of the birds increased and matched that the controls. Thus the effect of the drug was reversible. Addition of furazolidone to the feed at a concentration of 0.01% w/w for 28 days did not produce anorexia in chickens or affect the amount of 5-HT in the brain. Thus at this level, it is unlikely that the drug would produce adverse effects in poultry.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005260:Female; D005664:Furazolidone / Q000494:pharmacology*; D006815:Hunger / Q000187:drug effects*; D008297:Male; D012701:Serotonin / Q000378:metabolism; D013831:Thiamine / Q000037:antagonists & inhibitors*; D013835:Thiamine Pyrophosphate / Q000097:blood; D014422:Turkeys
D012701:Serotonin; D005664:Furazolidone; D013835:Thiamine Pyrophosphate; D013831:Thiamine