EFFECTS OF LEVELS OF SELECTED VITAMINS ON THE METABOLISM AFLATOXIN IN SOME ANIMAL SPECIES

Abstract

On account of the influence of vitamin A on biological membranes including the smooth endoplasmic reticulum, and on aflatoxin carcinogenicity and toxicity in other animals, the effect of vitamin A status on the metabolism of aflatoxin B1 and G1 in the rabbit was investigated in vitro in the 9,000 xg supernatant fraction of the liver. Male weanling rabbits were fed ad. lib, for 28 days a diet deficient in vitamin A or containing an excess of it preparatory to the enzyme assays. The demethylation of aflatoxin B1 but not G1 was significantly reduced in vitamin A deficiency. An excess of vitamin A had no significant effect on the demethylation of the two aflatoxins. Aflatoxin demethylation activity was generally higher than that of aflatoxin B1. The hydroxylation of aflatoxin B1 as represented by the production of aflatoxicol and aflatoxin M1 as well as the total amount of aflatoxin B1 metabolized, was not significantly altered by either a deficiency or excess of vitamin A. In view of the association of ascorbic acid with the drug metabolizing enzyme symtom and the fact that its metabolism is influenced by vitamin A status, the effect of simultaneous deprivation of dietary vitamins A and C on the hydroxylation and demethylation of aflatoxin B1 was studied in vitro in the 9,000 xg supernatant fraction and slices, respectively, of liver from male weanling guinea pigs deprived of vitamin A, vitamin C or both vitamins for 16 days. There were significant reductions in the amount of aflatoxin B1 metabolized and in the level of one structurally unknown metabolite, AFII, produced. The production of the other unknown metabolite, AF1, was significantly increased in a simultaneous deficiency of the two vitamins but was depressed by a deficiency of vitamin C, aflatoxin M1 production was not significantly altered by dietary deficiency of vitamin A, vitamin C or both vitamins. The demethylation of aflatoxin B1 by the liver slices was significantly reduced only when both vitamins were lacking. In order to ascertain whether the moderating influence of vitamin A status on the response of rats to Aflatoxin poisoning results from altered pattern of in vivo metabolism of the toxin, the liver and intestinal tissues of young male albino rats given a dose of aflatoxin B1 (1 mg/kg, i.p.) 35 days of after the commencement of feeding of vitamin A-deficient regimen, were extracted and the extracted aflatoxin metabolites analysed by thin layer chromatography. Chromatograms of the fluorescent aflatoxin B1 metabolites extracted 2 hr and 6 hr, respectively, after the administration of aflatoxin, revealed that vitamin A deficiency influenced the pattern of the in vivo metabolism of aflatoxin B1 in the liver and the disposition of these metabolites in the intestinal tissue whether or not the bile ducts were ligatured. In view of the role of vitamin A in blood coagulation, the influence of this vitamin on the anticoagulant action of aflatoxin B1 was astudied in rabbits, guinea pigs and rats given 1/20 of their respective LD50 doses of aflatoxins B1 daily as the last five days of feeding with vitamin A deficiency diets. The percentage increases in blood clothing time were significantly higher in vitamin A deficiency animals as compared with the controls in the three species studied. The implications of these results to the response of the animals to aflatoxin poisoning are discussed.