Effect of dietary ascorbic acid, cholesterol and PCB on cholesterol and bile acid metabolism in a rat mutant unable to synthesize ascorbic acid.
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.
Horio
F
F
Department of Agricultural Chemistry, Nagoya University, Japan.
Ozaki
K
K
Oda
H
H
Makino
S
S
Hayashi
Y
Y
Yoshida
A
A
D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000096:biosynthesis; D001206:Ascorbic Acid Deficiency / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D001835:Body Weight; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004032:Diet; D005243:Feces / Q000032:analysis; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D009929:Organ Size; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains
D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D011078:Polychlorinated Biphenyls; D002790:Cholesterol 7-alpha-Hydroxylase; D001205:Ascorbic Acid