Takahiro Mikami

Age, sex and source of hamster affect experimental cholesterol cholelithiasis

In the present study, we examined the effect of the following factors on a hamster model of cholesterol cholelithiasis: (i) the source of the golden Syrian hamsters (Sasco, Omaha, NE or Charles River, Wilmington, MA), (ii) the sex of the experimental animals and (iii) their age (4 wkvs. 8 wk of age). All hamsters were fed a semipurified diet which contained cholesterol (0.3%) and palmitic acid (1.2%). No cholesterol gallstones formed in any of the female hamsters regardless of age or source. The 4-week-old male hamsters from Sasco had the greatest incidence of gallstones (93%). The 8-week-old male hamsters tended to have a lower incidence of cholesterol gallstones than the younger ones, regardless of the commercial supplier (67vs. 93% for Sasco and 27vs. 40% for Charles River). Female hamsters has higher liver and serum cholesterol levels than the male hamsters; Charles River hamsters had lower serum cholesterol concentrations than the Sasco animals. Total biliary lipid concentrations were highest in Sasco male hamsters, but biliary cholesterol (mol%) was lower in the males than in the females (4.2–4.5%vs. 6.1–7.1%) regardless of age. The cholesterol saturation indices were higher in the Sasco females than the corresponding males; these values were lower in the Sasco hamsters than the Charles River animals, regardless of age or sex. The male Sasco hamsters had a higher total biliary bile acid concentration (98.9 mg/mL) than the Sasco females (58.9 mg/mL) and the Charles River animals (24.6% mg/mL for males and 38.2 mg/mL for females). The percentage of chenodeoxycholic acid in bile was significantly lower, and the percentage of cholic acid was higher in all females as compared to males. We conclude that there is a sex, age and “strain” difference in cholesterol cholelithiasis in hamsters; it is important to consider these factors when working with the hamster model of gallstone disease. All female hamsters were markedly resistant to the induction of cholesterol gallstone disease.

Effects of dietary fat and fatty acids on sterol balance in hamsters

Sterol balance studies, using both isotopic and chromatographic techniques, were carried out in hamsters fed semipurified diets to detect changes in sterol metabolism during the early period of the lithogenic stimulus. The balance studies examined animals in the first two weeks on the experimental lithogenic diets. The variables were as follows: dose of cholesterol (group 1, 0.05% vs. group 2, 0.2%); dietary fat (fatty acid) (group 2, butterfat vs. group 4, palmitic acid); source of hamster [group 2, Sasco (Omaha, NE) vs. group 3, Charles River (Wilmington, MA)]; average weight of animals (group 4, 60 g vs. group 5, 119 g). Animals in groups 1, 2, 3 and 5 maintained almost constant weight throughout the two-week balance study. Liver and plasma cholesterol levels increased in groups 2–5 with increasing dose of dietary cholesterol. The highest levels were found in group 4 (liver cholesterol, 32.7 mg/g; plasma cholesterol, 367 mg/dL). Sterol balance measurements showed that bile acid synthesis remained low (range 0.55–1.01 mg/d) for all groups regardless of the intake of dietary cholesterol (range, 3.27–20.90 mg/d). The dietary cholesterol absorbed from the intestine (range, 2.91–18.91 mg/d) was stored in the liver; this storage was reflected in the negative values for cholesterol balance for all groups (range, −0.70 to −14.97 mg/d). These studies did not reveal any correlations between parameters of sterol balance and cholelithiasis.