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Effect of Dietary Ascorbic Acid, Cholesterol and PCB on Cholesterol and Bile Acid Metabolism in a Rat Mutant Unable to Synthesize Ascorbic Acid¹

Department of Agricultural Chemistry, Nagoya University, Nagoya 464-01 Japan ^* Aburahi Laboratories, Shionogi Research Laboratories, Shionogi & Co., Ltd., Gotanda, Koga-gun, Shiga 520-34, Japan

The effect of acute or chronic ascorbic acid deficiency on the activity of hepatic cholesterol 7-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-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-hydroxylase and a lower excretion of fecal bile acids than in OD rats fed a basal diet containing an adequate level of ascorbic 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.

KEY WORDS: • ascorbic acid • ODS-od/od rat • cholesterol • bile acid • cholesterol 7-hydroxylase

¹ Supported in part by the grant of Elizabeth Arnold Fuji Foundation.

² To whom reprint requests should be addressed.

Manuscript received 10 December 1987. Revision accepted 27 October 1988.