Effect of ursodeoxycholic acid administration on bile acid composition in hamster bile.

The modification in the composition of bile acids in hamster by the administration of high dose of ursodeoxycholic acid (UDCA) was investigated. Male Golden Syrian hamsters were divided into five groups: a control group, two groups that received 0.5 g of UDCA per 100 g of standard diet during 30 and 60 days and another two groups that received 1 g of UDCA per 100 g of standard diet during 30 and 60 days. After ether anaesthesia the gallbladder was removed and bile was immediately aspirated. Bile acids were determined by high performance liquid chromatography (HPLC). Taurolithocholic (TLCA) and glycolithocholic acids (GLCA) increased significantly in all treated groups. The glyco/tauro ratio of 0.69 in controls became more than 1 in treated animals except in the case of lithocholic acid (LCA) conjugates which remained less than 1. UDCA derivatives increased proportionally to the administered dose and the cholic/cheno ratio diminished significantly. A moderate increase of 3- and 7-keto derivatives of chenodeoxycholic acid (CDCA) was observed in all treated groups but the above mentioned increment was especially evident in 3-keto derivatives. A high percentage of UDCA administered in the hamster was likely transformed to CDCA and the glyco conjugates of the bile acids were the predominant species except for the LCA derivatives.

[The effect of galbanic acid on the course of experimental hepatitis]. / Vliianie gal'banovoi kisloty na techenie éksperimental'nogo gepatita.

Administration of galbanic acid isolated from the roots of Ferula kopetdaghensis Eug. Kor. to rats orally in a dose of 50 mg/kg was found to improve the course of toxic hepatitis induced by fourfold subcutaneous injections of a 50% oil solution of CCl4. Galbanic acid produced much more earlier than in control normalization of the activity of the enzymes alanine- and aspartataminotransferase in blood serum, increased glycogen content and improved the parameters of the redox potential of lactic acid-pyruvic acid system in the liver. Galbanic acid exerted the antioxidant effect. In the animals with a developed hepatitis receiving galbanic acid there was a more rapid restoration of intensity of bile secretion, synthesis of bile acids and bilirubin, cholesterol excretion as compared with control.

[Methods of determining the concentration of total lipids and phosphorus in the bile]. / Sposoby opredeleniia kontsentratsii obshchikh lipidov i fosfora v zhelchi.

Standard kits of reagents, manufactured in the CSSR, intended for measurements of the blood serum and urinary lipids and phosphorus, were used for measurements of these component' concentrations in the bile. The levels of the total lipids and phosphorus in the bladder bile, measured with the use of this kit in normal subjects, did not essentially differ from those reported in literature.

[Polyunsaturated phosphatidylcholine and bile lipid composition]. / Fosfatidilcolina polinsatura e composizione lipidica della bile.

The lipid composition of bile and the molar percentages of its components (cholesterol, lecithin [Lec], and bile salts) are influenced by diet composition (for example the content of cholesterol) and during fasting. Molecular species of Lec can be affected by the species of dietary fatty acids (a high n-3 fatty acid content in the diet increases their proportion in biliary Lec). The administration of polyunsaturated Lec (EPL), rich in 18:2-18:2-PC, increases the percentage of linoleic acid at position 2 of biliary lecithin, which is often reduced in subjects with cholesterol gallstones.

[Correction of disorders of bile lipid-mineral composition as a method of preventing cholelithiasis]. / Korrektsiia narushenii lipidno-mineral'nogo sostava zhelchi kak metod profilaktiki zhelchnokamennoi bolezni.

A study of 60 patients with biliary tract diseases revealed different disorders of the lipid and mineral composition of bile of monotypical character but different by severity in patients with dyskinesias, cholecystitis and cholelithiasis. Silibor favours normalization of the lipid composition of bile, a dry protein mixture--the mineral composition quadevit--the mineral and lipid composition of bile.

Mercury-selenium interaction: distribution and excretion of 203Hg2+ in rats after simultaneous administration of selenite or selenate.

In female rats intravenously injected with 203HgCl2 (0.6 mg Hg2+ per kg body wt.) the effect of intraperitoneal administration of selenite or selenate (0.525 mg Se per kg body wt.) on distribution and excretion of 203Hg was studied. The content of 203Hg was lower in kidney and higher in liver and blood in the groups treated with selenate or selenite when compared with rats which received only mercury. The brain content of 203Hg was significantly increased in rats injected with selenite. Both selenium compounds injected immediately after mercury significantly decreased urinary as well as biliary excretion of 203Hg. A transient increase in the rate of biliary excretion of 203Hg during the first 2 h after administration was observed in rats treated with selenate. This finding seems to support the idea that the reduction of selenate to selenite in the body is not rapid but takes at least several hours.

Cholelithiasis in hamsters: effects of cholic acid and calcium on gallstone formation.

Dietary cholic acid (0.1%) and/or calcium (2.6% as calcium carbonate) were added to a semipurified diet containing cholesterol and ethynyl estradiol to determine whether the incidence of pigment and/or cholesterol gallstones would be changed. Male golden Syrian hamsters were fed the experimental diets for 96 days (Group 1, control; Group 3, cholic acid plus calcium) or only an average of 60 days (Group 2, 0.1% cholic acid). Animals in Group 2 became ill (weight loss, low food intake, diarrhea) possibly due to cholic acid (or deoxycholic acid) toxicity. Cholesterol gallstones and crystals were absent in all experimental groups. The incidence of pigment gallstones was: control, Group 1, 12/16; 0.1% cholic acid, Group 2, 3/13; and 0.1% cholic acid plus calcium, Group 3, 11/22. Cholic acid with or without calcium produced an elevation of both liver and plasma cholesterol: Group 2, 80.1 mg/g and 501 mg/dl; Group 3, 103.7 mg/g and 475 mg/dl vs Group 1, 65 mg/g and 209 mg/dl, respectively. The lithogenic indices of the bile were lower in Groups 2 and 3 compared to Group 1, controls, 0.45 and 0.58 vs 1.16, respectively. The extent of the portal tract pathology could not be correlated with the presence or absence of pigment gallstones or with the levels of lithocholic acid in the hamster bile. In summary, when semipurified diets were supplemented with ethynyl estradiol and cholic acid, with and without calcium supplementation, no cholesterol gallstones formed and the incidence of pigment gallstones was not altered.

Influence of legume intake on biliary lipids and cholesterol saturation in young Chilean men. Identification of a dietary risk factor for cholesterol gallstone formation in a highly prevalent area.

Chileans and North American Indians have one of the highest prevalence rates of cholesterol gallstones in the world. The most common theory to explain this has been the operation of some as yet undefined genetic risk factor in these populations. Searching for some common environmental factor for gallstones in Chileans and North American Indians, we found that beans and other legumes are common foods consumed by both populations. In this study we tested the hypothesis that legume intake may favor the production of biliary cholesterol supersaturation. We studied 20 young men subjected to a diet containing 120 g/day of legumes and a control diet without legumes for a period of 1 mo each. Both diets supplied identical quantities of energy, carbohydrates, protein, total fat, fiber, and cholesterol. Low-density lipoprotein cholesterol concentration decreased by 16% (p less than 0.001) after the legume diet. Biliary cholesterol saturation increased in 19 of the 20 subjects; the mean of the group markedly increased from 110% to 169% (p less than 0.001) after the legume diet. These results are consistent with the hypothesis that legume intake is a potential risk factor for cholesterol gallstone disease.

Effect of hyocholic acid on the prevention and dissolution of biliary cholesterol crystals in mice.

Gallstone prevention and dissolution were studied in a mouse model of cholesterol cholelithiasis using hyocholic acid (3 alpha, 6 alpha, 7 alpha-trihydroxy-5 beta-cholanic acid). Addition of hyocholic acid, 0.1 or 0.3%, in the lithogenic diet (1% cholesterol + 0.5% cholic acid) prevented the formation of cholesterol monohydrate crystals in 70 and 90% of cases, respectively. On the other hand, chow diet supplemented with 0.1 or 0.3% hyocholic acid dissolved cholesterol crystals in lithiasic mice in, respectively, 80 and 100% of cases within 12 days. In both protocols, biles were largely supersaturated with cholesterol; lecithin-cholesterol lamellar liquid crystals were responsible for the transport of the excess cholesterol content. The percentage of hydrophilic bile salts (hyocholic acid, hyodeoxycholic acid, beta-muricholic acid) in bile, although moderate (15-50% of total bile salts), appears to induce such liquid crystalline dispersion. This study demonstrates that the balance between hydrophilic and hydrophobic bile salts plays a major role in the prevention and dissolution of cholesterol crystals. It is also shown that the desaturation of biliary cholesterol is not a prerequisite for gallstone dissolution.

Alcohol protects against cholesterol gallstone formation.

Epidemiologic studies have suggested that alcohol intake may protect against cholelithiasis. Gallstone formation was studied in 20 prairie dogs fed a 0.4% cholesterol-supplemented liquid diet. In ten animals, ethanol provided 35% of total calories. In ten pair-fed controls, ethanol was replaced with isocaloric maltose. After 3 months the gallbladders were inspected for gallstones, and gallbladder bile was analyzed. Cholesterol macroaggregates were present in all controls and pigment concretions were noted in five. No stones were observed in ethanol-fed animals. Bile in the ethanol group contained less cholesterol than the controls (5.60 +/- 0.71 vs. 9.16 +/- 0.61 mmol/L, p less than 0.05) while phospholipids, total bile acids, and bilirubin were unchanged. The resulting cholesterol saturation index was reduced in the ethanol group (0.81 vs. 1.22, p less than 0.05). The ratios of trihydroxy to dihydroxy bile acids were also different (2.07 +/- 0.25 in ETOH vs. 3.29 in controls, p less than 0.05). The bile calcium concentration was higher in control animals presumably secondary to the use of complex sugars (5.36 +/- 0.37 vs. 3.77 +/- 0.32 mmol/L, p less than 0.05). These results confirm that ethanol inhibits cholesterol gallstone formation. They further suggest that this effect is dependent on reductions of biliary cholesterol and selective changes in bile acid concentrations.

Gallstone prevention in prairie dogs: comparison of chow vs. semisynthetic diets.

The effects of a standard rodent chow were compared with those of a semisynthetic diet of known composition (with and without added cholesterol) in the prairie dog model of cholesterol cholelithiasis. Gallstone incidence was 40% higher in animals fed a semisynthetic diet plus cholesterol compared to chow plus cholesterol. The semisynthetic diet plus cholesterol caused significant increases in tissue cholesterol levels (serum, liver and bile) and lithogenic index, but significant decreases in the activity of hepatic 3-hydroxy-3-methyl-glutaryl coenzyme A reductase and cholesterol 7 alpha-hydroxylase compared to chow plus cholesterol. Histologic study of liver sections revealed that the semisynthetic diet plus cholesterol resulted in moderate to marked portal tract changes characterized by bile duct proliferation, inflammatory infiltration and fibrosis, whereas the cholesterol-supplemented chow diet caused only slight bile duct proliferation with minimal inflammation and fibrosis in the portal areas. Dietary hyodeoxycholic acid prevented cholesterol gallstones and biliary cholesterol crystals when added to either chow plus cholesterol or semisynthetic plus cholesterol diets. The hyodeoxycholic acid supplements also prevented the development of severe histopathologic alterations along the portal tracts. Biliary cholesterol levels were elevated in prairie dogs fed cholesterol plus hyodeoxycholic acid; these animals had liquid crystals in the bile, and hyodeoxycholic acid and its 6 beta-isomer became the major biliary bile acids. A semisynthetic diet plus cholesterol is superior to a high cholesterol chow diet for gallstone formation and prevention studies, but in prolonged feeding experiments, the potential hepatotoxicity of this diet in the prairie dog must be appreciated.

Biliary and urinary excretion of metals in humans.

Fifteen metals (lead, cadmium, arsenic, inorganic mercury, organic mercury, iron, manganese, magnesium, chromium, zinc, copper, nickel, cobalt, tin, and aluminum) were determined in the hepatic bile and urine collected simultaneously from three Japanese individuals (2 males, 1 female). The presence of these metals was classified as follows: hepatic biliary concentrations were higher than urinary concentrations (lead, arsenic, and iron); urinary concentrations were higher than hepatic biliary concentrations (cadmium, inorganic mercury, tin, cobalt, magnesium, chromium, copper, zinc, and nickel); hepatic biliary concentrations were almost equal to urinary concentrations (manganese and organic mercury); and relationship between hepatic biliary and urinary concentrations changed occasionally (aluminum). Eight essential metals (iron, manganese, magnesium, zinc, chromium, copper, nickel, and cobalt) were detected at considerable concentrations in hepatic bile. Accounting for the daily flow volume of hepatic bile and the reabsorption of these metals, the supplementation of these metals should occur during treatment of diseases accompanied by loss of hepatic bile.