Abstract
A metabolic product was formed from ochratoxin B by rat liver microsomal fractions in the presence of NADPH. It was isolated from the incubation mixture by extraction, thin-layer chromatography, high-pressure liquid chromatography, and crystallization. On the basis of mass and nuclear magnetic resonance spectroscopy, the structure is suggested to be 4-hydroxyochratoxin B. The Km for the formation of 4-hydroxyochratoxin B was determined, and the hydroxylation of ochratoxin A was not altered by the presence of ochratoxin B. Rats were given ochratoxin A or B, or a mixture of both intraperitoneally. The ratios of the three metabolites, ochratoxin A, (4R)-4-hydroxyochratoxin A, and ochratoxin alpha, excreted in the urine did not change in the presence of ochratoxin B. Ochratoxin B was metabolized to 4-hydroxyochratoxin B and ochratoxin beta, but in a different ratio than for the ochratoxin A metabolites. When given intraperitoneally, ochratoxin beta was excreted within 24 h. In rats treated with ochratoxin A alone, the food intake was reduced by 50%, and histologically severe lesions, degeneration, and necrosis were observed in the proximal tubules. When ochratoxin A and B given in combination, the animals were clinically unaffected and histologically there was only slight damage of proximal tubules. These observations indicate that ochratoxin B considerably reduces the toxic effects of ochratoxin A.
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- Creppy E. E., Størmer F. C., Kern D., Röschenthaler R., Dirheimer G. Effects of ochratoxin A metabolites on yeast phenylalanyl-tRNA synthetase and on the growth and in vivo protein synthesis of hepatoma cells. Chem Biol Interact. 1983 Nov;47(2):239–247. doi: 10.1016/0009-2797(83)90160-6. [DOI] [PubMed] [Google Scholar]
- Creppy E. E., Størmer F. C., Röschenthaler R., Dirheimer G. Effects of two metabolites of ochratoxin A, (4R)-4-hydroxyochratoxin A and ochratoxin alpha, on immune response in mice. Infect Immun. 1983 Mar;39(3):1015–1018. doi: 10.1128/iai.39.3.1015-1018.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doster R. C., Sinnhuber R. O., Pawlowski N. E. Acute intraperitoneal toxicity of ochratoxin A and B derivatives in rainbow trout (Salmo gairdneri). Food Cosmet Toxicol. 1974 Aug;12(4):499–505. doi: 10.1016/0015-6264(74)90063-7. [DOI] [PubMed] [Google Scholar]
- Elling F. Demonstration of ochratoxin A in kidneys of pigs and rats by immunofluorescence microscopy. Acta Pathol Microbiol Scand A. 1977 Mar;85A(2):151–156. doi: 10.1111/j.1699-0463.1977.tb00412.x. [DOI] [PubMed] [Google Scholar]
- Hansen C. E., Dueland S., Drevon C. A., Størmer F. C. Metabolism of ochratoxin A by primary cultures of rat hepatocytes. Appl Environ Microbiol. 1982 Jun;43(6):1267–1271. doi: 10.1128/aem.43.6.1267-1271.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanisawa M., Suzuki S. Induction of renal and hepatic tumors in mice by ochratoxin A, a mycotoxin. Gan. 1978 Aug;69(4):599–600. [PubMed] [Google Scholar]
- Krogh P., Hald B., Pedersen E. J. Occurrence of ochratoxin A and citrinin in cereals associated with mycotoxic porcine nephropathy. Acta Pathol Microbiol Scand B Microbiol Immunol. 1973 Dec;81(6):689–695. doi: 10.1111/j.1699-0463.1973.tb02261.x. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Patterson D. S., Roberts B. A., Small B. J. Metabolism of ochratoxins A and B in the pig during early pregnancy and the accumulation in body tissues of ochratoxin A only. Food Cosmet Toxicol. 1976 Oct;14(5):439–442. doi: 10.1016/s0015-6264(76)80183-6. [DOI] [PubMed] [Google Scholar]
- Steyn P. S., Holzapfel C. W. The synthesis of ochratoxins A and B metabolites of Aspergillus ochraceus Wilh. Tetrahedron. 1967 Nov;23(11):4449–4461. doi: 10.1016/s0040-4020(01)88843-8. [DOI] [PubMed] [Google Scholar]
- Støren O., Holm H., Størmer F. C. Metabolism of ochratoxin A by rats. Appl Environ Microbiol. 1982 Oct;44(4):785–789. doi: 10.1128/aem.44.4.785-789.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Størmer F. C., Hansen C. E., Pedersen J. I., Hvistendahl G., Aasen A. J. Formation of (4R)- and (4S)-4-hydroxyochratoxin A from ochratoxin A by liver microsomes from various species. Appl Environ Microbiol. 1981 Dec;42(6):1051–1056. doi: 10.1128/aem.42.6.1051-1056.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Størmer F. C., Pedersen J. I. Formation of 4-hydroxyochratoxin A from ochratoxin A by rat liver microsomes. Appl Environ Microbiol. 1980 May;39(5):971–975. doi: 10.1128/aem.39.5.971-975.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Størmer F. C., Støren O., Hansen C. E., Pedersen J. I., Aasen A. J. Formation of (4R)- and (4S)-4-hydroxyochratoxin A and 10-hydroxyochratoxin A from Ochratoxin A by rabbit liver microsomes. Appl Environ Microbiol. 1983 Apr;45(4):1183–1187. doi: 10.1128/aem.45.4.1183-1187.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van der Merwe K. J., Steyn P. S., Fourie L. Mycotoxins. II. The constitution of ochratoxins A, B, and C, metabolites of Aspergillus ochraceus Wilh. J Chem Soc Perkin 1. 1965 Dec;:7083–7088. doi: 10.1039/jr9650007083. [DOI] [PubMed] [Google Scholar]
- Visconti A., Bottalico A. High levels of ochratoxins A and B in moldy bread responsible for mycotoxicosis in farm animals. J Agric Food Chem. 1983 Sep-Oct;31(5):1122–1123. doi: 10.1021/jf00119a050. [DOI] [PubMed] [Google Scholar]


