Aminopyrine N-demethylation by rats with liver cirrhosis

Reichen, Jürg; Arts, B. P.; Schafroth, Urs; Zimmermann, A.; Zeltner, T. B.; Zysset, Thomas

doi:10.1016/0016-5085(87)90433-1

Cited by 76 publications

(22 citation statements)

References 32 publications

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“…Cirrhosis was induced in rats weighing 150-180 g by chronic exposure to phenobarbital and carbon tetrachloride for 12 wk according to McLean et al (19) as previously described (18); treatment was withheld 2 wk before the study, a time sufficient for the phenobarbital effects to disappear (8). Untreated littermates kept under identical conditions served as controls.…”

Section: Methodsmentioning

confidence: 99%

“…Aminopyrine and galactose metabolism were studied by breath tests previously described in detail from this laboratory (8,17) On the third day, the animals were anesthetized with pentobarbital (50 mg/kg i.p. ), a blood sample for determination of ALT, alkaline phosphatase and serum bile acids was obtained and portal pressure measured manometrically.…”

Section: Methodsmentioning

confidence: 99%

“…Microsomal fractions were prepared by differential centrifugation and the first 100,000 g supernatant taken as cytosolic fraction (8). Cytochrome P-450 content and the kinetics of ABT were determined by methods referenced previously (8) in homogenate and in the microsomal fraction.…”

Section: Methodsmentioning

confidence: 99%

“…Cytochrome P-450 content and the kinetics of ABT were determined by methods referenced previously (8) in homogenate and in the microsomal fraction. Galactokinase activity was determined in the cytosolic fraction by a radiometric assay described by Shin-Buehring et al (22).…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, little data are available on liver cell volume. We have recently demonstrated a bimodal distribution of liver cell volume in animals with cirrhosis of the liver, about half having maintained and half having decreased liver cell volume (8).…”

Section: Introductionmentioning

confidence: 94%

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Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

Reichen

Egger²,

Ohara³

et al. 1988

J. Clin. Invest.

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We investigated the determinants of hepatic clearance functions in a rat model of liver cirrhosis induced by phenobarbital/CCI4. Aminopyrine N-demethylation (ABT), galactose elimination (GBT), and serum bile acids (SBA) were determined in vivo. The livers were then characterized hemodynamically: intrahepatic shunting (IHS) was determined by microspheres and sinusoidal capillarization by measuring the extravascular albumin space (EVA) by a multiple indicator dilution technique. The intrinsic clearance was determined by assaying the activity of the rate-limiting enzymes in vitro. Hepatocellular volume (HCV) was measured by morphometry.ABT and SBA, but not GBT, differentiated cirrhotic from normal liver. IHS ranged from normal to 10%; all cirrhotic livers showed evidence of sinusoidal capillarization (reduced EVA). The cirrhotic livers showed a bimodal distribution of HCV, HCV being decreased in 50% of the cirrhotic livers.Multivariate analysis showed EVA and portal flow to be the main determinants of microsomal (ABT) and cytosolic (GBT) clearance function; SBA, by contrast, were determined solely by IHS.We conclude that sinusoidal capillarization is the main determinant of hepatic clearance, while serum bile acids reflect intrabepatic shunting. These findings emphasize the importance of alterations of hepatic nutritional flow to explain reduced clearance function in cirrhosis of the liver.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

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Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

Reichen

Egger²,

Ohara³

et al. 1988

J. Clin. Invest.

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31P and1H NMR spectroscopic studies of liver extracts of carbon tetrachloride-treated rats

et al. 1999

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Polycystic liver disease: Quantitation of parenchymal and cyst volumes from computed tomography images and clinical correlates of hepatic cysts

et al. 1988

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Polycystic liver disease is a common manifestation of autosomal dominant polycystic kidney disease. However, factors that regulate hepatic cystogenesis have not been defined, and the effect of cyst formation on hepatic parenchymal mass has not been studied. We validated computed tomographic methods for measuring volumes from computed tomographic images using plastic-agar models and demonstrated that measured volumes were within 10% of actual volumes. The validated methods were used to measure hepatic parenchymal, hepatic cyst and kidney volumes in 25 subjects with polycystic liver disease and nine controls without autosomal dominant polycystic kidney disease. Hepatic cyst volume varied considerably in the 25 subjects with polycystic liver disease (20 to 7,148 ml), but hepatic parenchymal volume was not altered by hepatic cysts and was similar to that of controls (polycystic liver disease vs. controls: 1,357 +/- 185 vs. 1,319 + 340 ml). Total liver volume increased linearly as cyst volume increased (slope = 1.02 +/- 0.05, r = 0.994). Nine of 18 women with polycystic liver disease had massive hepatic cysts (cyst: parenchymal volume greater than 1; range of cyst volumes from 1,354 to 7,148 ml), and the other nine had cyst volumes (20 to 399 ml) similar to men with polycystic liver disease (25 to 1,107 ml). Total kidney volume, a measure of renal cystic disease, did not correlate with either total liver volume or the volume of hepatic cysts. The data indicate that hepatic parenchymal volume is preserved in polycystic liver disease despite massive cystic involvement and that women are uniquely susceptible to massive hepatic cystic disease.

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Aminopyrine N-demethylation by rats with liver cirrhosis

Cited by 76 publications

References 32 publications

Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

31P and1H NMR spectroscopic studies of liver extracts of carbon tetrachloride-treated rats

Polycystic liver disease: Quantitation of parenchymal and cyst volumes from computed tomography images and clinical correlates of hepatic cysts

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