Pharmacology and toxicology of carbon tetrachloride in the sheep. IV. Reduction and augmentation of toxicity by selenium

Abstract

Susceptibility of sheep to toxic effects of carbon tetrachloride (CCl4) was assessed by determining the increase in plasma levels of isocitric dehydrogenase (ICD) and glutamic transaminase (GOT) and by other criteria. Susceptibility was increased by oral administration of 1 mg of selenium (Se) as sodium selenite plus 100 i.u. of tocopherol acetate on alternate days for 120 days, 2 mg Se per day for 21 days, and 6 mg Se per day for 6 days, before dosing with CCl4. Susceptibility was reduced by smaller total amounts of Se, and by oral doses of 6 mg Se per day for 3 days, a single oral or intramuscular dose of 5 or 12 mg c. 20 hr, or 5 or 12 mg orally 10–20 min, before dosing with CCl4. One 5 mg dose at 20 hr and a second 20 min before CCl4 was more effective than either alone. Sheep from two different sources differed considerably in their susceptibility to CCl4. In the more susceptible sheep Se administration reduced susceptibility to a level comparable with that shown by the naturally resistant animals. Administration of Se to sheep dosed with CCl4 and then given a high-protein diet resulted in lower GOT levels, milder clinical signs, and a great reduction in mortality. In field tests on properties with a recent history of CCl4 poisoning, oral administration of 5 mg Se about 20 min before CCl4 significantly reduced susceptibility. Administration of Se to fluke-infested sheep did not protect the liver fluke (Fasciola hepatica) against CCl4.

The Preventive Effect of Nicotinic Acid on Carbon Tetrachloride Toxicity in Sheep

“…Kanics & Rubinstein (1968) showed that carbon tetrachloride poisoned animals were unable to resynthetize liver glycogen and it seems possible that animals surviving acute experiments have a decreased liver glycogen content for a long time. Kondos & McClymont (1967) used sodium selenite and tocopherol acetate to prevent carbon tetrachloride toxicity in sheep. The resuMs were principally the same as in the P'resent study.…”

“…Later it was shown that nicotinic acid also reduced the histopathological liver changes in carbon tetrachloride poisoned sheep (Gallagher 1960). Other agents effective in preventing the toxic effects of carbon tetrachloride are antioxidants (Gallagher 1961, 1962, Kondos & McClymont 1967. Gallagher (1962) found that in animals treated with antioxidants the pyridine nucleotides in the liver were maintained at normal levels despite carbon tetrachloride administration.…”