Abstract

This study is aimed at establishing whether there is a public health hazard resulting from consumption of meat and dairy products derived from livestock feeding on tansy ragwort (Senecio jacobea), a widely dispersed plant containing the hepatotoxic pyrrolizidine alkaloids. The toxicity of milk and tissue from cows and goats will be initially determined in feeding studies with rats. We will also study the absorption, excretion, distribution and metabolism of seneciphylline and jacobine, the two principal pyrrolizidine alkaloids from tansy ragwort, in three species of laboratory animals, the rat (susceptible) and the rabbit and guinea pig (resistant), and in two species of lactating farm animals, the cow (susceptible) and the goat (resistant). Particular emphasis will be placed on isolating and characterizing reactive metabolites of the pyrrolizidine alkaloids, establishing whether covalent binding of such metabolites to tissue constituents occurs, and in establishing the biochemical mechanism(s) for toxicity of the alkaloids to mammals.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA022524-08
Application #
3165832
Study Section
Toxicology Study Section (TOX)
Project Start
1977-07-01
Project End
1987-05-31
Budget Start
1985-12-01
Budget End
1987-05-31
Support Year
8
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Oregon State University
Department
Type
Earth Sciences/Resources
DUNS #
053599908
City
Corvallis
State
OR
Country
United States
Zip Code
97339

  Publications

Chung, Woon-Gye; Buhler, Donald R (2004) Differential metabolism of the pyrrolizidine alkaloid, senecionine, in Fischer 344 and Sprague-Dawley rats. Arch Pharm Res 27:547-53
Chung, W G; Buhler, D R (1995) Major factors for the susceptibility of guinea pig to the pyrrolizidine alkaloid jacobine. Drug Metab Dispos 23:1263-7
Chung, W G; Miranda, C L; Buhler, D R (1995) A cytochrome P4502B form is the major bioactivation enzyme for the pyrrolizidine alkaloid senecionine in guinea pig. Xenobiotica 25:929-39
Chung, W G; Buhler, D R (1994) The effect of spironolactone treatment on the cytochrome P450-mediated metabolism of the pyrrolizidine alkaloid senecionine by hepatic microsomes from rats and guinea pigs. Toxicol Appl Pharmacol 127:314-9
Reed, R L; Miranda, C L; Kedzierski, B et al. (1992) Microsomal formation of a pyrrolic alcohol glutathione conjugate of the pyrrolizidine alkaloid senecionine. Xenobiotica 22:1321-7
Miranda, C L; Reed, R L; Guengerich, F P et al. (1991) Role of cytochrome P450IIIA4 in the metabolism of the pyrrolizidine alkaloid senecionine in human liver. Carcinogenesis 12:515-9
Miranda, C L; Chung, W; Reed, R E et al. (1991) Flavin-containing monooxygenase: a major detoxifying enzyme for the pyrrolizidine alkaloid senecionine in guinea pig tissues. Biochem Biophys Res Commun 178:546-52
Williams, D E; Reed, R L; Kedzierski, B et al. (1989) The role of flavin-containing monooxygenase in the N-oxidation of the pyrrolizidine alkaloid senecionine. Drug Metab Dispos 17:380-6
Williams, D E; Reed, R L; Kedzierski, B et al. (1989) Bioactivation and detoxication of the pyrrolizidine alkaloid senecionine by cytochrome P-450 enzymes in rat liver. Drug Metab Dispos 17:387-92
Reed, R L; Ahern, K G; Pearson, G D et al. (1988) Crosslinking of DNA by dehydroretronecine, a metabolite of pyrrolizidine alkaloids. Carcinogenesis 9:1355-61

Showing the most recent 10 out of 17 publications