Graduate Thesis Or Dissertation
 

Influence of dietary factors on tansy ragwort toxicosis in rats and horses

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  • Several experiments were conducted to investigate the effect of dietary factors such as amino acids, B vitamins, butylated hydroxyanisole (BHA) and phenobarbital on pyrrolizidine alkaloid toxicosis in rats and horses. The influence of St. John's wort, bracken, comfrey, and alfalfa on tansy ragwort toxicity was also examined. Effects of dietary tansy ragwort (Senecio jacobaea), comfrey (Symphytum officinale), bracken (Pteridium acquilinum) and alfalfa (Medicago sativa) on hepatic drug-metabolizing enzymes in rats were measured. Tansy ragwort and bracken increased (P<0.05) the activity of glutathione transferase and epoxide hydrolase. Comfrey and alfalfa increased (P<0.05) the activity of aminopyrine Ndemethylase. Feeding bracken or St. John's wort (Hypericum perforatum) in conjunction with tansy ragwort did not influence chronic toxicity of tansy ragwort as assessed by rat survival time. Dietary tansy ragwort resulted in increased (P<0.05) hepatic copper levels; the other plants did not affect copper levels. The results do not suggest any major interaction in the toxicity of tansy ragwort with bracken or St. John's wort. Dietary supplementation of rats with branched chain amino acids (BCAA: leucine, isoleucine, valine) did not alter their susceptibility to chronic poisoning by tansy ragwort (Senecio jacobaea), which contains hepatotoxic pyrrolizidine alkaloids (PA). Phenobarbital in the diet, which alters liver microsomal enzyme activity, also did not alter susceptibility to PA poisoning. A combination of BHA, cysteine and BCAA did increase (P<.05) survival time of rats fed tansy ragwort. Dietary BHA and cysteine increased the survival times of rats injected with the PA monocrotaline, with evidence that addition of vitamin B₁₂ and folic acid improved the effectiveness of this treatment. In a chronic feeding trial with tansy ragwort, a combination of BHA and cysteine increased (P<.05) the survival times of rats, showing protective activity against PA poisoning. A mixture of B-complex vitamins, or vitamin B₁₂-folic acid, was not effective in improving the response. Dried tansy ragwort, which contains pyrrolizidine alkaloids, was fed as 10% of a complete diet to horses, with and without a mixture of additives. The additives provided a dietary supplement equivalent to 1% cysteine, 0.75% BHA, 200 ppb vitamin B₁₂ and 5 ppm folic acid. The additives did not alter tansy ragwort toxicity, as assessed by survival time, liver histology, bromosulphalein clearance rate and serum gamma glutamyl transpeptidase activity. In horses fed tansy ragwort, bromosulphalein clearance rate was a sensitive indicator of liver damage, and declined to a level of about 20% of control values. Gamma glutamyl transpeptidase levels showed considerable variability but in general were elevated in animals fed tansy ragwort. Liver iron and copper levels were elevated, and liver zinc declined in tansy ragwort-fed horses.
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