Abstract
The toxic effects of helenalin and tenulin were investigated in dogs and mice, and Helenium microcephalum was studied in sheep. The compounds tested were toxic to dogs in the following order: mexicanin-E, helenalin, helenalin propionate, and tenulin. In addition, the toxicity of helenalin was enhanced by prior administration of furosemide or acetyl-promazine maleate to dogs. The electrocardiographic (ECG II) manifestations of helenalin or tenulin toxicity in dogs or Helenium microcephalum toxicity in sheep were: increased P, R, T, and U wave voltages; ST segment deviations; AV dissociation; bundle branch block; and ventricular aberration. Pathophysiologic effects in dogs include tachycardia, hypotension, and respiratory distress. Lesions observed in both dogs and sheep included hepatocellular necrosis, bile stasis, renal tubular nephrosis, myocardial necrosis, and edema, necrosis, and hemorrhage of the gall bladder. Edema and necrosis also occurred in the rumen and reticulum in sheep. Single oral administration of helenalin or tenulin to mice produced a significant (p < 0.05) thiol depletion and subsequent induction (significant for the helenalin treated mice) in stomach, small intestine, kidney, and liver, compared to physiological saline (0.9% NaCl; 5 ml/kg) treated controls. Multiple daily doses of helenalin also significantly increased thiols in the small intestine and kidney, but decreased thiols in the liver of mice. Concurrent administration of ethoxyquin (0.5%)-methionine hydroxy-analog (0.5%) in the diet proved effective in raising liver, stomach, and small intestine thiols and in reducing the toxicity of helenalin and tenulin in mice. Nonprotein thiol levels in sheep treated with Helenium microcephalum ranged from 2.19 (mu)M/g to 6.7 (mu)M/g (+OR-) 1.66 (mu)M/g in the liver and 3.74 (mu)M/g to 5.63 (mu)M/g (+OR-) 0.96 (mu)M/g in the kidney at necropsy; control values were 7.25 (mu)M/g (+OR-) 0.293 (mu)M/g in the liver and 2.77 (mu)M/g (+OR-) 0.275 (mu)M/g in the kidney of untreated sheep. It is concluded that helenalin, tenulin, and Helenium microcephalum in the sheep produce qualitatively similar toxic effects on the electrocardiogram and in the pathological lesions. Furthermore, there is an important relationship between the toxicity of helenalin or tenulin and the thiol status of the liver, kidney, stomach and small intestine.
Anderson, Anthony Car (1984). Studies in the toxicity of helenalin, tenulin, and Helenium microcephalum. Texas A&M University. Texas A&M University. Libraries. Available electronically from
https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -411126.