Effect of dietary ascorbic acid, cholesterol and PCB on cholesterol and bile acid metabolism in a rat mutant unable to synthesize ascorbic acid

J Nutr. 1989 Mar;119(3):409-15. doi: 10.1093/jn/119.3.409.

Abstract

The effect of acute or chronic ascorbic acid deficiency on the activity of hepatic cholesterol 7 alpha-hydroxylase and fecal excretion of bile acids was investigated in ODS-od/od (OD) rats (a rat mutant unable to synthesize ascorbic acid) fed a purified basal diet or purified diets containing either cholesterol (2%) or polychlorinated biphenyl (PCB) (200 mg/kg). In OD rats, the dietary requirement of ascorbic acid to maintain normal growth and normal levels of cholesterol in serum and liver is about 300 mg of ascorbic acid/kg diet. In OD rats fed the basal diet, acute or chronic ascorbic acid deficiency did not affect the activity of hepatic cholesterol 7 alpha-hydroxylase and fecal excretion of bile acids. However, in OD rats fed diets containing either cholesterol or PCB, acute ascorbic acid deficiency caused a higher level of serum cholesterol, a lower activity of hepatic cholesterol 7 alpha-hydroxylase and a lower excretion of fecal bile acids than in OD rats fed a basal diet containing an adequate level of ascrobic acid. It is concluded that acute ascorbic acid deficiency causes a hypercholesterolemia due to the depression of bile acid synthesis in OD rats fed a purified diet with cholesterol or PCB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / administration & dosage*
  • Ascorbic Acid / biosynthesis
  • Ascorbic Acid Deficiency / metabolism*
  • Bile Acids and Salts / metabolism*
  • Body Weight
  • Cholesterol / blood
  • Cholesterol / metabolism*
  • Cholesterol 7-alpha-Hydroxylase / metabolism
  • Cholesterol, Dietary / pharmacology*
  • Cytochrome P-450 Enzyme System / metabolism
  • Diet
  • Feces / analysis
  • Lipid Metabolism
  • Liver / enzymology
  • Male
  • Organ Size
  • Polychlorinated Biphenyls / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Rats, Mutant Strains

Substances

  • Bile Acids and Salts
  • Cholesterol, Dietary
  • Cytochrome P-450 Enzyme System
  • Cholesterol
  • Polychlorinated Biphenyls
  • Cholesterol 7-alpha-Hydroxylase
  • Ascorbic Acid