Effect of pyridoxine on the disposition and lymphopenic effects of 2-acetyl-4(5)-tetrahydroxybutyl imidazole in the rat.
1. 2-Acetyl-4(5)-tetrahydroxybutyl imidazole (THI) administered orally to rats markedly decreased the peripheral blood lymphocyte count within 16-24 h. The lymphopenic effect of THI was prevented by co-administration of pyridoxine. 2. 14C-THI, administered orally, was absorbed in a dose-dependent manner and excreted unmetabolized. These processes were not affected by co-administration of pyridoxine. 3. In contrast, the rate of excretion of 14C-THI administered i.v. was increased by both dietary and parenterally-administered pyridoxine, and pyridoxine decreased the amount of radiolabel associated with lymphoid tissues. 4. The results show that the lymphopenic effect of THI is not sustained once it is excreted, and indicate that pyridoxine and THI may compete for the same binding site in lymphoid tissues.
Phillips
J A
JA
DHSS Department of Toxicology, St Bartholomew's Hospital Medical College, London, UK.
Paine
A J
AJ
D000818:Animals; D001667:Binding, Competitive; D004032:Diet; D005215:Fasting; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D007700:Kinetics; D008198:Lymph Nodes / Q000378:metabolism; D008231:Lymphopenia / Q000139:chemically induced*; D008297:Male; D010581:Peyer's Patches / Q000378:metabolism; D011736:Pyridoxine / Q000494:pharmacology*; D051381:Rats; D013154:Spleen / Q000378:metabolism
D007093:Imidazoles; C049929:2-acetyl-4(5)-tetrahydroxybutylimidazole; D011736:Pyridoxine