Nutritional influences affecting senecio toxicity in laboratory animals Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/bv73c368c

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  • The objective of this research project was to evaluate the toxicity of local pyrrolizidine alkaloid containing plants and to examine the influence of dietary protein, with particular reference to the amino acid cysteine, upon this toxicity. Senecio vulgaris (common groundsel) was shown to be more toxic than Senecio jacobaea (tansy ragwort). On a dry matter basis, common groundsel contained .206% alkaloid while tansy ragwort contained 181% alkaloid. Survival time was less (P ≤ .05) for rats fed 5% common groundsel in the diet than for rats fed 5% tansy ragwort. At equivalent doses, the alkaloid isolated from common groundsel was more toxic when injected intraperitoneally into rats than the alkaloid from tansy ragwort. In two experiments with growing rats, supplemental dietary cysteine was shown to provide partial protective activity against dietary tansy ragwort toxicity as measured by survival time, growth rate, total serum protein, serum albumin and liver weight. One percent methionine had no influence on survival time or performance. The inclusion of 1% dietary cysteine in the ration of mature rats receiving 10% tansy ragwort did not show any protective effects. Females seemed to be more severely affected than males. Japanese quail (Coturnix coturnix japonica) were found to be resistant to the toxic effects of 10% dietary tansy ragwort. Day old White Rock X White Cornish chicks were acutely susceptable to the toxic actions of dietary tansy ragwort, with 1% supplemental dietary cysteine producing a detrimental effect. It has been suggested that sulfhydryl groups may play a role in detoxication of pyrrolizidine alkaloid metabolites, such as conjugation with glutathione and subsequent excretion as mercapturic acids. Two metabolism studies were performed in an attempt to elucidate the protective action of cysteine against pyrrolizidine alkaloid toxicity in growing rats. Supplemental 1% dietary cysteine had no effect upon liver sulfhydryl levels. The cysteine did significantly decrease the level of liver-bound pyrrolic metabolites 2 hours post injection of 100 mg alkaloid/ kg body weight and theoretically the resulting toxicity. It is therefore suggested that either undetectably small alterations in sulfhydryl levels can provide protection or that cysteine is acting in some way other than covalently bonding to the reactive pyrrole. Cysteine had no effect on the in vitro conversion of tansy ragwort alkaloids to pyrrolic metabolites by rat liver microsomes.
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