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Vitamin E and hepatotoxic agents

2*. Lipid peroxidation and poisoning with orotic acid, ethanol and thioacetamide in rats

Published online by Cambridge University Press:  09 March 2007

J. Bunyan ,
M. A. Cawthorne ,
A. T. Diplock  and
J. Green
J. Bunyan
Affiliation:
Beecham Research Laboratories, Vitamins Research Station, Walton Oaks, Tadworth, Surrey
M. A. Cawthorne
Affiliation:
Beecham Research Laboratories, Vitamins Research Station, Walton Oaks, Tadworth, Surrey
A. T. Diplock
Affiliation:
Beecham Research Laboratories, Vitamins Research Station, Walton Oaks, Tadworth, Surrey
J. Green
Affiliation:
Beecham Research Laboratories, Vitamins Research Station, Walton Oaks, Tadworth, Surrey
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Abstract

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1. Fatty liver was induced in 4-month-old male rats by oral dosing with ethanol. The marked increase in liver fat was not accompanied by a rise in lipid peroxides.

2. Homogenates were prepared from the livers of vitamin E-deficient rats and incubated with ethanol. In the concentration range of 10–50 μl/3 ml, ethanol increased the production of malondialdehyde. Methanol, which is not a hepatotoxin, showed a similar effect at 10–35 μl/3 ml homogenate. These findings indicate that the pro-oxidative effect of alcohols in vitro is unrelated to their hepatotoxic action in vivo.

3. Fatty liver was induced in 3.g-month-old, vitamin E-deficient male rats by oral dosingwith ethanol. The effect of pretreatment with vitamin E and N,N'-diphenyl-p-phenylenediamine (DPPD) was studied. D-α-Tocopheryl acetate, given as three doses of 350 mg/kg at 48, 24 and 2 h before the ethanol, failed to decrease the fat accumulation and seemed rather to increase the fat content of the liver. DPPD, given as three doses of 600 mg'kg at similar intervals before the ethanol dose, reduced the fat content of the liver almost to normal.

4. Weanling rats of both sexes were given a vitamin E-deficient diet containing 1% orotic acid for 15 days to induce fatty liver. Dietary supplements of D-a-tocopheryl acetate (500 ppm), selenium (I ppm) or DPPD (100 ppm) did not reduce the lipid accumulation. Lipid peroxides and malondialdehyde levels were lower in the livers of animals treated with orotic acid than in controls, regardless of the presence of vitamin E.

j. Liver necrosis was produced in 9-week-old female vitamin E-deficient rats by the intra-peritoneal injection of zoo mg thioacetamide. Promethazine hydrochloride (Phenergan), given intraperitoneally as two doses (25 mg/kg at the same time as the thioacetamide and 12.5 mg/kg 6 h later), markedly reduced the necrosis. D-α-Tocopheryl acetate, given as two oral doses of 1000mg/kg 48 h and 24 h before the thioacetamide, tended to exacerbate the necrosis.

6. The results are discussed in relation to the question of lipid peroxidation as a cause of hepatotoxicity.

Type
Research Article
Information
British Journal of Nutrition , Volume 23 , Issue 2 , June 1969 , pp. 309 - 317
Copyright
Copyright © The Nutrition Society 1969

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