Resistance of the Suckling Guinea Pig to Lithocholic Acid-Induced Cholestasis†

Lewittes, Malka; Tuchweber, B; Weber, Andrée; Roy, Claude; Yousef, Ibrahim M.

doi:10.1002/hep.1840040322

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…The hepatocytic ultrastructure revealed characteristic features described earlier for normal guinea pigs [24], The only conspicu ous change was the accumulation of lipid droplets in the 12-hour group ( fig. 1).…”

Section: Liver Weight Composition and Morphologymentioning

confidence: 60%

“…and a PE-50 catheter was inserted into the right jugular vein. The common bile duct was then cannulated with a PE-50 catheter as described elsewhere [24). Animals were kept anesthe tized during the entire experiment and body temper ature was kept at 37 °C with a heating lamp.…”

Section: Methodsmentioning

confidence: 99%

“…The mechanisms responsible for this development are not known, but on the basis of the observations of Simon et al [39], we postulate a greater number of bile acid car rier proteins at canalicular membrane sites. In earlier studies with lithocholate we showed that binding of the bile acid to cyto solic protein in newborn liver was signifi cantly less than that in adult liver [24], Other investigators have determined the content of cytosolic bile acid binding protein (S) and found that in newborns it is lower than in adult animals [40], Thus, the diminished protein available for binding would in fluence the free pool of bile acid that could be released from hepatocyte via back diffu sion across sinusoidal membranes [41] or across canalicular membranes by precocious maturation of the canalicular carrier protein.…”

Section: Discussionmentioning

confidence: 99%

“…I4C radioactivity in bile was assessed by liquid scintilla tion spectrometry, as described earlier [24].…”

Section: A Nalytical Proceduresmentioning

confidence: 99%

“…However, when developing rats and guinea pigs are given lithocholic acid, their susceptibility to cholestasis is signifi cantly lower than that of adults. This is asso ciated with reduced binding of lithocholate to cytosolic protein and a more efficient secretion of the bile acid in the bile of new borns [24,25], The precise mechanism of this resistance to cholestasis is not clearly defined, but it was suggested that the bile acid pool size may play a role by increasing the secretory capacity for the toxic bile acid [25].…”

Section: Introductionmentioning

confidence: 99%

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Development of Bile Secretory Function in the Neonatal Guinea Pig

Tuchweber

Ducruet²,

Perea³

et al. 1990

Neonatology

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Maturation of hepatic bile formation and lipid secretion were examined in neonatal guinea pigs in an attempt to explain the earlier observation that the neonate (15 days old) is less susceptible to lithocholate-induced cholestasis than the adult. Bile flow and bile acid secretion were lowest at 12 h postpartum and increased to attain a maximum at 15 days. Thereafter, values decreased to a level which was not significantly different from that at 3 days of age. Bile acid analysis indicated the presence of chenodeoxycholic acid, 7-ketolithocholic acid and ursodeoxycholic acid in bile at all ages. But, at 15 days ursodeoxycholic acid was a major contributor to total bile acid secretion. Phospholipid and cholesterol secretion increased between the 1st and the 3rd day of age but decreased markedly at 15 days. This indicated an uncoupling of biliary lipid secretion and endogenous bile acids which was related in part to the nature of the bile acids secreted. Serum bile acid levels were markedly increased at 15 days of age. This hypercholanemia may reflect a rapid expansion of the bile acid pool including an enhanced bile acid secretion which could explain in part the resistance to the lithocholate cholestasis by increasing the secretory capacity for the toxic bile acid.

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Section: Liver Weight Composition and Morphologymentioning

confidence: 60%

Section: Methodsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…I4C radioactivity in bile was assessed by liquid scintilla tion spectrometry, as described earlier [24].…”

Section: A Nalytical Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of Bile Secretory Function in the Neonatal Guinea Pig

Tuchweber

Ducruet²,

Perea³

et al. 1990

Neonatology

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Parenteral nutrition–associated liver disease and the role for isolated intestine and intestine/liver transplantation†

2006

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Parenteral nutrition-associated liver disease (PNALD) is the most devastating complication of long-term parenteral nutrition therapy. Because its progression is typically insidious and its long-term consequences are generally underappreciated, PNALD is often recognized too late, when liver injury is irreversible. When end-stage liver disease (ESLD) develops in these patients, most potential interventions are futile and transplantation of both an intestine and a liver becomes the only viable option, despite the relatively poor outcomes associated with this combined procedure. Although likely multifactorial in origin, the etiology of PNALD is poorly understood. Early clinical intervention with a combination of nutritional, medical, hormonal, and surgical therapies can be effective in preventing liver disease progression. If these interventions fail, intestinal transplantation should be performed expeditiously before development of ESLD mandates simultaneous inclusion of a liver graft as well. (HEPATOLOGY 2006;43:9-19.)

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Hepatic Bile Salt Sulfotransferases in the Rat

Kane,

Chen

1991

J. pediatr. gastroenterol. nutr.

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SummaryBile salt sulfotransferase (BSS) activity for the fetal bile acid, 3β‐hydroxy‐5‐cholenoate, was first detected in the fetus at 18–19 days of gestation and was twofold greater than for glycolithocholate. The near‐term (20–21 days of gestation) and newborn pup BSS activity was only 5–10% of that in maternal liver. The 3β‐hy‐droxy‐5‐cholenoate sulfotransferase activity rose by the second day of life to levels observed in the mature male, and to activities greater than the mature female by the time of weaning at 3 weeks of age. Sex differences in 3β‐hydroxy‐5‐cholenoate sulfotransferase activity developed during adolescence (28–35 days of age), resulting in fivefold greater activity in the mature female compared with the male. Two isoenzyme activities (BSS I and BSS II) were identified in both sexes during development by DEAE‐Sephadex A‐50 ion‐exchange chromatography of liver cytosol. In the fetal and newborn liver, only one isoenzyme activity was distinctly identified for both monohydroxy bile acids, corresponding to BSS I in older rats. After the first week of life, both BSS I and BSS II exhibited activity like glycolithocholate, but only one peak of activity was identified for 3β‐hydroxy‐5‐cholenoate, corresponding to BSS I. The 3β‐hydroxy‐5‐cholenoate sulfotransferase activity in the mature male was only 20% of the mature female because of a decline in BSS I activity in the male during adolescence. BSS I and II were further purified by taurocholate‐Sepharose 4B chromatography. BSS I had a low affinity toward taurocholate passing through the column, whereas BSS II was absorbed and could be eluted from the column with 0.2 M NaCl. BSS I had four times the activity for 3β‐hydroxy‐5‐cholenoate vs. glycolithocholate, whereas the relative activity of BSS II for 3β‐hydroxy‐5‐cholenoate was only 6% of that for glycolithocholate. BSS I was completely inhibited by 0.1 m M 3‐ketolithocholate, whereas BSS II activity was inhibited only 13%. BSS I activity was enhanced by Co2+ and Zn2+, whereas BSS II activity was inhibited by these divalent ions. We concluded that the monohydroxy bile acids were sulfated by two distinct isoenzymes that could be separated by taurocholate‐Sepharose 4B chromatography. 3β‐Hydroxy‐5‐choleno‐ate was sulfated by BSS I, an isoenzyme regulated by gonadal hormones, which appeared to explain the marked sex differences in 3β‐hydroxy‐5‐cholenoate sulfotransferase activities in mature rats.

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Resistance of the Suckling Guinea Pig to Lithocholic Acid-Induced Cholestasis†

Cited by 12 publications

References 23 publications

Development of Bile Secretory Function in the Neonatal Guinea Pig

Development of Bile Secretory Function in the Neonatal Guinea Pig

Parenteral nutrition–associated liver disease and the role for isolated intestine and intestine/liver transplantation†

Hepatic Bile Salt Sulfotransferases in the Rat

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