Effect of food restriction on hepatotoxicity of carbon tetrachloride in rats.
Five-week-old Sprague-Dawley rats of both sexes were assigned to two types of feeding condition. One was fed ad libitum (AL) on commercial chow and another was fed a restricted amount of the chow (FR), approximately 75% of that fed in the AL condition. In each feeding condition, animals were orally administered carbon tetrachloride (CCl4) at levels of 0 (control), 0.1 or 0.2 ml/kg 6 days a week for 8 weeks. Lesions of the liver (hepatic cellular degeneration and fibrosis) and of the kidney (proximal tubular vacuolation and glomerular sclerosis) induced by CCl4 were aggravated in the FR group. The FR-control showed a higher metabolic activity of aniline in the liver than the AL-control group. Plasma lipid-peroxide (LPO) level was higher in the AL-control group than in the FR-control group. With CCl4 0.2 ml/kg treatment, however, the plasma LPO level was reversed between the AL and the FR groups. Taking together these somewhat unexpected results, it was concluded that (1) 25% food restriction increases toxicity of repeatedly administered CCl4 in rats, and (2) aggravation of CCl4 toxicity may be partly due to enhanced metabolic activation of CCl4 resulting from food restriction.
Seki
M
M
Laboratory of Toxicology, Hatano Research Institute, Kanagawa, Japan.
Kasama
K
K
Imai
K
K
D000818:Animals; D001711:Biotransformation; D002251:Carbon Tetrachloride / Q000493:pharmacokinetics / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D002149:Energy Intake; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride