Enhancement by Secretin of the Apparently Maximal Hepatic Transport of Bilirubin in the Rat

Ricci, Giovanni; Michiels, R; Fevery, Johan; Groote, J. De

doi:10.1002/hep.1840040414

Cited by 17 publications

(4 citation statements)

References 38 publications

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“…Ductular reabsorption is almost nonexistent in this species (11), and secretin causes only a slight increase of bile flow, apparently originating at the hepatocellular level (22). Choleresis produced by cefmetazole in our experiments could be explained by stimulation of an electrolyte transport mechanism or by the osmotic activity of cefmetazole in bile.…”

Section: Methodsmentioning

confidence: 46%

Biliary excretion and choleretic effect of cefmetazole in rats

González

Fernández

Mariño

et al. 1989

Antimicrob Agents Chemother

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The effect of cefmetazole, a broad-spectrum cephalosporin, on bile flow and composition in rats was studied. Intravenous injection of cefmetazole at doses ranging from 40 to 400 ,umol/kg of body weight led to an increase in its biliary concentration and excretion rate, with a maximum at 30 min after injection. Excretion of cefmetazole into bile was associated with a marked choleresis. The magnitude of the increase in bile flow was dose dependent, with a maximal increase at a dose of 200 ,umol/kg. Cefmetazole administration did not affect the secretion of bile acids or their osmotic activities, whereas the bile acid-independent bile flow increased by 49% at a dose of 200 ,umol/kg. Cefmetazole administration at a dose of 200 timol/kg significantly increased the biliary outputs of sodium, potassium, chloride, and bicarbonate (+36, +56, +28, and +31%, respectively) compared with outputs of controls. A linear relationship was observed between bile flow and cefmetazole excretion, 44 pil of bile being produced per ,umol of cefmetazole excreted into bile. Our results demonstrate that cefmetazole induces choleresis by stimulating bile acid-independent bile flow. This effect appears to be partly due to the osmotic properties of cefmetazole transported into bile.Cefmetazole sodium [7-,-cyanomethylthioacetamide-7-amethoxy -is a semisynthetic derivative of cephamycin. This cephalosporin has a broad antimicrobial spectrum, is efficient against gram-positive and gram-negative bacteria, and shows high resistance to attack by different P-lactamases (23,31). Several studies have confirmed its usefulness in the treatment of different kinds of infections and in prophylactic administration after surgical wounds (11). Since the drug was first released for clinical use, its pharmacokinetics and metabolism in humans and different animals have been described elsewhere (23,25,26). The antibiotic is excreted via urine and bile, with significant species differences in the participation of both routes (18,26,27). The biliary excretion of cefmetazole has been shown to be closely related to the bile/plasma ratio of bile acids (27) and dependent on the amount of bile flow and liver function (26).Appropriate antibiotic therapy in treatment of biliary tract infections must take into account the transfer of the drug into bile. The purpose of this study was to examine the effects of biliary elimination of cefmetazole on the formation of bile in rats. The influences of cefmetazole on the bile acid-dependent and -independent components of bile flow and on bile composition were evaluated. [vol/vol]); flow rate, 1.0 ml/min. The detection limit was 0.1 ,ug of cefmetazole per ml; the variation coefficient varied between 3.7 and 4.2% of the high and low concentrations assayed, respectively (12, 23).The possible existence of a correlation between the variables studied was investigated by linear regression analysis,

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Section: Methodsmentioning

confidence: 46%

Biliary excretion and choleretic effect of cefmetazole in rats

González

Fernández

Mariño

et al. 1989

Antimicrob Agents Chemother

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“…the effect on dibromosulfophthalein is the oppo site [14], Differences are also apparent be tween species for the same organic anion and even appear at strain level [34], Regarding the influence of bile flow on bilirubin secre tion, it has also been suggested that there is a relationship between them in the rat [16]. Data recently obtained by Ricci et al [3,39] in the conscious rat are conflicting; on the one hand, a decrease in canalicular bile flow after administration of somatostatin is not accompanied by a decrease in the Tm of bili rubin [3], on the other hand, the administra tion of secretin induced an increase in both the Tm of bilirubin and bile flow [39], More over, a lack of these effects of secretin was reported in isolated rat liver [39]. In both conscious rat and isolated rat liver, however, secretin was seen to induce an increase in hepatic UDP glucuronyl transferase activity [39].…”

Section: Discussionmentioning

confidence: 96%

“…Data recently obtained by Ricci et al [3,39] in the conscious rat are conflicting; on the one hand, a decrease in canalicular bile flow after administration of somatostatin is not accompanied by a decrease in the Tm of bili rubin [3], on the other hand, the administra tion of secretin induced an increase in both the Tm of bilirubin and bile flow [39], More over, a lack of these effects of secretin was reported in isolated rat liver [39]. In both conscious rat and isolated rat liver, however, secretin was seen to induce an increase in hepatic UDP glucuronyl transferase activity [39]. It is difficult at this stage to decide whether the increase in the Tm of bilirubin depends on the increase in secretin-induced bile flow or whether there is no relation between both aspects.…”

Section: Discussionmentioning

confidence: 99%

Influence of Dehydrocholate on Bilirubin Transport into Bile in the Rat

Marin¹,

González²,

Esteller³

1986

Digestion

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The effect of an intravenous infusion of sodium dehydrocholate on the maximum biliary transport (Tm) of bilirubin was studied in Wistar rats anesthetized with sodium pentobarbitone. Infusion of the synthetic bile salt at 0.24 μmol/min/100 g gave rise to a marked increase in bile flow (69%). The biliary output of taurocholate, phospholipid or cholesterol, compounds which from mixed micelles in bile, was not modified. Neither did the Tm of bilirubin undergo any significant changes, with drops in the bile concentration of the pigment. Our experimental results revealed that bile flow induced by dehydrocholate is not a determining factor of the Tm of bilirubin in the rat.

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“…gates at saturating conditions [6,7] was also increased after treatment of animals with secretin [2] and glucagon [4],…”

Section: Introductionmentioning

confidence: 99%

Subcellular Localization of UDP-Glucuronyltransferase by Differential Centrifugation

Ricci

Michiels²,

Muñoz³

et al. 1989

Enzyme

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Subcellular fractionation of liver homogenates from treated rats was carried out in order to study the mechanism of action of the gastrointestinal polypeptides on glucoronidation. Rats were treated for 90 min with an intravenous infusion of secretin (0.4 cU/h/100 g body weight), glucagon (100 μg/h/100 g body weight) and vasoactive intestinal polypeptide (VIP) (300 ng/h/100 g body weight); controls were sham-treated rats. For comparison, another group of animals was treated with a daily injection of phenobarbitone (10 mg/kg), a well-established enzyme inducer. Treatment with the different polypeptides produced minor changes in the subcellular localization of the enzyme. The bulk of activity was always recovered in the microsomal fraction, as identified by both differential centrifugation and the enrichment in specific activity of glucose-6-phosphatase, esterase and NADPH-cytochrome c reductase. Secretin produced a specific increase of bilirubin glucuronidation, more evident in all nuclear fractions. Glucagon increased both bilirubin and p-nitrophenol glucuronidation in all subcellular fractions. VIP had a selective action on p-nitrophenol conjugation of similar extent in nuclear and microsomal fractions. The type of changes observed is suggestive of physicochemical modifications occurring into the cell, perhaps at the membrane environment of different organelles, able to modify the overall conjugation of different substrates by the cell.

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Enhancement by Secretin of the Apparently Maximal Hepatic Transport of Bilirubin in the Rat

Cited by 17 publications

References 38 publications

Biliary excretion and choleretic effect of cefmetazole in rats

Biliary excretion and choleretic effect of cefmetazole in rats

Influence of Dehydrocholate on Bilirubin Transport into Bile in the Rat

Subcellular Localization of UDP-Glucuronyltransferase by Differential Centrifugation

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