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• W2099212933 abstract "Relationships can be demonstrated between the acute hepatotoxicity of some pyrrolizidine alkaloids and the amounts of pyrrolic metabolites found in livers of rats given the alkaloids. Liver pyrrole levels are proportional to doses of an alkaloid administered two hours earlier. While alkaloids differ widely in toxicity, the amounts of pyrrolic metabolites in livers a few hours after LD50 doses are relatively constant, suggesting that toxic effects are caused by such metabolites, though the possibility of additional toxic metabolites is not excluded. The toxicity of an alkaloid and the liver pyrrole level is affected by sex, diet and predosing with compounds which affect the hepatic microsomal enzymes. Retrorsine and monocrotaline are considerably more toxic to male rats than to females. Pretreatment with phenobarbitone increases the susceptibility of female rats but in males the toxicity of retrorsine is halved by a week's phenobarbitone pretreatment. Short-term pretreatment of male rats with phenobarbitone causes increases in liver levels of pyrrolic metabolites from retrorsine which are evidently not due to altered microsomal enzyme activity. Pretreatment of male rats with SKF 525A, or prefeeding a sucrose diet, reduces both the toxicity and the liver pyrroles after retrorsine. Retrorsine N-oxide is considerably less toxic when administered intraperitoneally than when given orally. This is discussed in relation to distribution and metabolism." @default.
• W2099212933 created "2016-06-24" @default.
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• W2099212933 date "1972-09-01" @default.
• W2099212933 modified "2023-09-25" @default.
• W2099212933 title "Acute hepatotoxicity and pyrrolic metabolites in rats dosed with pyrrolizidine alkaloids" @default.
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• W2099212933 doi "https://doi.org/10.1016/0009-2797(72)90027-0" @default.
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