The Effect of Prior Treatment with Phenobarbitone, Dicophane (DDT) and β-Diethylaminoethyl Phenylpropyl Acetate (SKF 525A) on Experimental Intoxication of Sheep with the Plant Myoporum deserti Cunn

Abstract

Single oral doses of 2.25 and 5 g/kg body weight of powdered leaf of Myoporum deserti, the main toxic principle of which was tfehydrongaione, caused death of sheep within 1 to 3 days of dosing. Post-mortem findings included liver necrosis, haemorrhagic inflammation of the lower alimentary tract, subcutaneous and subserous haemorrhages, fatty degeneration of the tubular epithelium of the kidneys and of the myocardium and sometimes terminal pulmonary oedema. If SKF 525A was given to sheep before dosing with 1 g/kg of toxic leaf, the toxicity was significantly reduced compared with controls, suggesting that the hepatotoxic oils required metabolism by the hepatic microsomal drug metabolizing enzymes in order to produce toxicity. However, pretreatment with phenobarbitone or DDT compounds used to enhance the activity of these enzymes did not significantly increase the toxicity of the plant for the sheep. The zonal distribution of the liver lesion in control sheep was mainly periportal although midzonal and centrilobular lesions occurred in some livers. In the phenobarbitone and DDT treated animals the liver lesion was consistently periportal necrosis while in the SKF 525A treated animals the injury was centrilobular. This suggested that the level of the hepatic drug metabolizing enzymes at the time of poisoning was involved in determining the toxicity of the plant for the animal and the zonal distribution of injured cells in the liver. The findings are similar to previously reported observations of the effects of these drug pre treatments on ngaiotie toxicity in the mouse.