Changes in nutritional status associated with obstructive jaundice and biliary drainage in rats (original) (raw)
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Effective Treatment of Unconjugated Hyperbilirubinemia With Oral Bile Salts in Gunn Rats
Gastroenterology, 2009
We tested the hypothesis that oral administration of bile salts, which are known to increase the biliary excretion of unconjugated bilirubin (UCB), decreases unconjugated hyperbilirubinemia in the Gunn rat model. Methods: Adult Gunn rats were fed a standard diet or the same diet supplemented with 0.5 weight % ursodeoxycholic acid (UDCA) or cholic acid (CA) for 1 or 6 weeks. UCB and urobilinoids, a family of intestinal UCB breakdown products, were determined in plasma, feces, or both. After 6 weeks of treatment, tracer 3 H-UCB was administered intravenously to determine steady-state UCB kinetics over the next 60 hours. Results: One-week treatment with UDCA or CA decreased plasma UCB concentrations by 21% and 30%, respectively (each P < .01). During the first 4 days of treatment, both UDCA and CA increased the combined fecal excretion of UCB and urobilinoids (؉52% and ؉32%, respectively; each P < .01). Prolongation of treatment to 6 weeks caused a persistent decrease in plasma UCB concentrations to ϳ40% below baseline (each bile salt P < .001). 3 H-UCB kinetic studies showed that UDCA and CA administration decreased UCB pool size (؊33% and ؊32%, respectively; each P < .05) and increased UCB fractional turnover (؉33% and ؉25%, respectively; each P < .05). Conclusions: Dietary bile salt administration induces a large, persistent decrease in plasma UCB concentrations in Gunn rats. Both UDCA and CA enhance UCB turnover by increasing its fecal disposal. These results support the application of oral bile salt treatment in patients with unconjugated hyperbilirubinemia.
Fat Absorption and Metabolism in Bile Duct Ligated Rats
Annals of Nutrition and Metabolism, 2001
Background: Bile excretion is obstructed in children with extrahepatic bile duct atresia (EHBA) resulting in fat malabsorption and disturbed lipid metabolism. Aim: Investigate if the bile duct ligated rat exhibits similar deviations as patients with EHBA under different feeding conditions. Methods: 6 bile duct ligated Wistar rats and 12 matched paired controls were randomised over 3 feeding groups. Rats were killed 16 or 30 days postsurgery. Faeces, blood and livers were collected. Fat absorption was evaluated, markers for cholestasis and the fatty acid composition of serum phospholipids (PL) and cholesterol esters (CE) were determined. Fatty acid desaturation activities in liver microsomes were measured. Results: Cholestatic bile duct ligated rats have a lower fat absorption coefficient and a lower fraction of 18:2n-6 and 18:3n-3 in serum triglycerides than their controls. This demonstrates that bile duct ligated rats suffer from fat malabsorption. In contrast to the observations in serum triglycerides, 18:2n-6 and 18:3n-3 were not reduced in serum PL and CE of cholestatic rats. Overflow of 18:2n-6 rich biliary PL in the general circulation could contribute to this observation. In agreement with what was found in man, serum PL of cholestatic rats have a higher 16:0/18:0 ratio, increased monoenes and reduced unsaturated fatty acids. However, no differences were observed in microsomal desaturation activities. Conclusion: Cholestatic bile duct ligated rats exhibit similar deviations in serum fatty acid composition as found in patients with EHBA, therefore they can be used as a model for this human disease.
Study of the long-term effects of selective biliary obstruction (SBO)
Research in Experimental Medicine, 1981
Selective biliary obstruction (SBO) is a model of partial cholestasis in the rat in which the bile duct draining the median lobe is ligated and transected; the remaining biliary tree remains intact. Other authors introduced this experimental model and studied morphological and biochemical modifications in the liver after 2 days from surgery. They suggest that an adaptation may o c c u r. Choosing some markers of cholestasis and some other markers of various cytoplasmic organelles, we studied the long-term effects that occur in serum and in total liver homogenate of selectively obstructed rats as compared to controls. Alkaline phosphatase activity and bile acids content, which were significantly higher than controls in serum and in total liver homogenate of the median lobe after 2 and 8 days from SBO, returned to normal range values after 30 days. Cytochrome-oxidase and glucose-6-phosphatase activity in total homogenate of the SBO median lobe remains perfectly similar to the control values in time. Results, together with morphological observations, suggest that cholestasis is present immediately after operation, then decreases gradually and disappears finally. The obstructed median lobe seems to cope with cholestasis.
Significance of Altered Bilirubin Subfractions in Bile Following Hepatectomy
Journal of Surgical Research, 2002
Materials and methods. Rats underwent either laparotomy or partial hepatectomy (Hx). Daily intraperitoneal injections of lipopolysaccharide (LPS) or natural saline were administered for 3 days following surgery. Total serum bilirubin levels and proportions of BDG and bilirubin in bile were measured until Day 5 after the operation. Hepatic levels of UDPglucuronic acid (UDP-GA), UDP-glucose, NAD ؉ , and total adenine nucleotides (TAN) and activities of UDPglucuronyltransferase (UDP-GT) and UDP-glucose dehydrogenase were measured on Day 4.
British Journal of Surgery, 1990
Renal failure complicating obstructive jaundice (OJ) is probably linked to reduction of the extracellular water compartment. To elucidate the mechanism by which OJ leads to isotonic water depletion we studied a group of rabbits with OJ after common bile duct ligation (n = 17) and another group of sham operated rabbits (n = 14) for 10 days. Water intake and balance for two study periods (1–4 and 7–10 days after operation) were calculated. Renal function, sodium balance and plasma atrial natriuretic factor were determined on the fourth and tenth days after operation. Water intake and balance were lower in the OJ group both in the first study period (230 versus 519 ml/days 1–4, P<0–001; and—2·4 versus 279 ml/days 1–4, P < 0·0001 respectively) and in the second study period (260 versus 865 ml/days 7–10, P< 0·0001; and 11 versus 379 ml/days 7–10, P< 0·000 7 respectively). Sodium intake was negligible in the OJ group both on day four (0·73 versus 7·75 mM/24 h, P<0·0001) and...