Abstract-Changes of cholesterol, phospholipid, triglyceride or bile acid levels in serum, liver, bile and feces after the treatment with alloxan were examined in Wistar strain male rats. Serum cholesterol, phospholipid and triglyceride levels and liver cholesterol level markedly increased but liver phospholipid and triglyceride levels remained un changed. The lipid levels in serum very low density and low density lipoproteins were elevated but those in high density lipoprotein were not. Bile flow was not changed but biliary secretion of cholesterol, phospholipid and bile acids markedly increased. Among the biliary bile acid components, cholic acid markedly increased but the amount of chenodeoxycholic acid was similar to that of normal rats. Fecal excretion of deoxy cholic acid increased but that of lithocholic and hyodeoxycholic acids decreased, and a-, Q and oi-muricholic acids did not change, thus, the total amount of fecal bile acids remained unchanged.Hepatic cholesterol synthesis was markedly depressed, while cholesterol 7a-hydroxylase activity did not change and cytochrome P-450 content was elevated by about 40 %. From such evidence, it was apparent that synthesis of cholic acid increased while that of chenodeoxycholic acid decreased and the total amount of bile acids synthesized did not change in the diabetic rats. Furthermore, marked increase of the pool size of cholic acid and hepatic secretion of cholic acid stimulated the absorption of lipids and produced a hyperlipidemia in the diabetic rats.Serum cholesterol and triglyceride levels in diabetics increase markedly and this increase is related to a high incidence of atherosclerosis (1, 2) and cholesterol gallstones (3). Diabetic rats, treated with alloxan or streptozotocin, also developed marked hyperlipidemia (4-10) with a higher incidence of cardiovascular lesions when fed a high cholesterol diet (7). The mechanism by which marked hyperlipidemia is produced in diabetic rats is not fully under stood, but Bierman et al. (6) have postulated that the intake of dietary fat is related to the manifestration of hyperlipidemia, and Nervi et al. (9) found an increase in biliary secretion and daily synthesis of bile acids in alloxan diabetic rats and concluded that hypercholester olemia is due to an increase in cholesterol absorption. We examined cholesterol or bile acid level in serum, liver, bile and feces of alloxan diabetic rats in an attempt to elucidate the mechanism underlying hypercholesterolemia.
MATERIALS AND METHODSMale Wistar rats weighing approximately 300 g were kept in an air-conditioned room (25 --1 °C, 50-60% humidity) lighted 12 hr a day (08:00 to 20:00) and maintained on a com
The effects of cholesterol feeding on serum and liver cholesterol levels, fecal and biliary bile acid levels, bile acid pool size and bile acid composition were examined in 2-, 12-and 24-month-old male
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