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Hydrolysis rates of pyrrolizidine alkaloids derived from Senecio jacobaea.

Many of the commonly studied pyrrolizidine alkaloids (PAs) are built upon the subgroup retronecine (RET), which is released from the parent molecule by either base catalyzed or enzymatic hydrolysis of the ester linkages. The rate of appearance of RET in a hydrolytic study would thus reflect the rate of hydrolysis for the PA being tested. We have developed a gas chromatographic (GC) method to measure the release of RET from incubations of PAs with the guinea pig carboxylesterase, GPH1. The PAs tested were the following: jacobine (JAB), jacozine (JAZ), retrorsine (RES), and seneciphylline (SNP). The KmS for SNP and JAZ were determined to be 64.9 and 349.2 microM, respectively. In addition, a qualitative assessment of hydrolytic activity toward a radiolabelled mixture of retrorsine/riddelliine (RES/RIL) was performed with HPLC and radiometric detection.

Animals↗

Influence of tansy ragwort (Senecio jacobaea), dietary copper, and feed restriction on the subcellular distribution of minerals in rat liver.

Young male rats were pair-fed diets containing 0 or 5% tansy ragwort (TR), with each diet containing 0 or 50 micrograms/g copper. Other animals given TR-free diets were also maintained as ad libitum controls. After 5 weeks of feeding these diets, the rats were killed for the determination of the trace metal contents of liver fractions. TR with no dietary copper supplement increased the calcium content of all hepatic fractions except nuclei and debris, but had no effect on the subcellular concentrations of copper, zinc, or iron. When 50 micrograms/g copper was included in the TR diet, the subcellular distribution of copper, iron, and calcium was altered. This alteration was shown by an increase (as compared to pair-fed controls given copper-supplemented diet with no TR) in the copper content of all fractions except cytosol, the iron content of all fractions, and the calcium content of mitochondria, microsomes, lysosomes, and cytosol. Feed restriction (pair-fed versus ad libitum controls) using diets with no additional copper produced an increase in the copper and calcium contents of mitochondria; the copper, zinc, and calcium contents of cytosol; and the calcium content of lysosomes. Addition of 50 micrograms/g copper to the diets abolished these effects of feed restriction. These findings suggest that the subcellular distribution of copper, zinc, iron, and calcium in rat liver is subject to perturbation by pyrrolizidine alkaloid-containing diet, dietary copper, and feed restriction.

Animals↗

Effects of dietary supplementation with ethoxyquin, magnesium oxide, methionine hydroxy analog, and B vitamins on tansy ragwort (Senecio jacobaea) toxicosis in beef cattle.

Dried tansy ragwort containing pyrrolizidine alkaloids was fed as 2.5% of a complete (control) diet to Hereford steers, with and without (basal) a mixture of additives. The additives provided a dietary supplement equivalent to 0.1% ethoxyquin, 1% methionine hydroxy analog, 2% MgO, 2.7 mg of vitamin B6/kg of diet, 50 micrograms of vitamin B12/kg of diet, 0.45 g of folic acid/kg of diet, and 0.2 g of cobalt/kg of diet. The additives did not alter tansy ragwort toxicity substantially, as assessed by liver histologic changes, sulfobromophthalein clearance rate, and serum gamma-glutamyl transpeptidase activity. After 281 days, 1 of 4 steers fed the basal diet was alive, whereas 3 of 4 steers in the basal plus additives group were alive, suggesting some protective activity. The chronic lethal dose of tansy ragwort in steers was 3.6% of initial body weight.

Animals↗