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Modifications of liver bile acids pool during modulation of rat hepatocarcinogenesis by phenobarbital and nafenopin

Modifications of liver bile acids pool during modulation of rat hepatocarcinogenesis by... As previously demonstrated, chronic administration of phenobarbital (0.05% in the drinking water) and of nafenopin (0.1% in the diet) increases the incidence and the kinetics of appearance of liver cancers. If bile acids play a key role in liver carcinogenesis, it might thus be expected that treatments like phenobarbital or nafenopin, which positively modulate that process, also modify their hepatic pool. The aim of the present study was to analyze the modifications of the liver bile acid pool during the modulation of liver carcinogenesis by phenobarbital and nafenopin. The animals were submitted to the hepatocarcinogenic initiation-selection (IS) procedure adapted from Solt and Farber. As compared to basal diet, the chronic feeding of phenobarbital significantly increased the total concentrations of liver bile acids both at weeks 9 and 17. That increase was mainly due to a change in the concentration of β-muricholic acid and hyodeoxycholic acid and, to a lesser extent, of chenodeoxycholic acid and α-muricholic acid. In contrast, feeding a diet containing nafenopin led to a significant decrease in the concentration of liver bile acids, due to a complete disappearance of chenodeoxycholic acid and muricholic acid, and a decrease in the concentration of hyodeoxycholic acid. Carcinomas appearing in IS phenobarbital-treated rats contain fewer bile acids than the surrounding parenchyma (because of the decrease in deoxycholic acid and ursodeoxycholic acid) whereas the malignant tumors appearing in IS nafenopin-treated rats have essentially the same pattern of bile acids as the surrounding parenchyma. During modulation of liver carcinogenesis by phenobarbital and nafenopin, changes in bile acid metabolism definitively take place but they are both quantitatively and qualitatively different. Therefore, the perturbations of liver bile acid homeostasis occurring in such a carcinogenic protocol do not seem to be implicated in the positive modulation induced by phenobarbital or nafenopin treatment. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Toxicology Springer Journals

Modifications of liver bile acids pool during modulation of rat hepatocarcinogenesis by phenobarbital and nafenopin

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References (22)

Publisher
Springer Journals
Copyright
Copyright © Springer-Verlag 1994
Subject
Biomedicine; Pharmacology/Toxicology; Occupational Medicine/Industrial Medicine; Environmental Health; Biomedicine, general
ISSN
0340-5761
eISSN
1432-0738
DOI
10.1007/s002040050087
Publisher site
See Article on Publisher Site

Abstract

As previously demonstrated, chronic administration of phenobarbital (0.05% in the drinking water) and of nafenopin (0.1% in the diet) increases the incidence and the kinetics of appearance of liver cancers. If bile acids play a key role in liver carcinogenesis, it might thus be expected that treatments like phenobarbital or nafenopin, which positively modulate that process, also modify their hepatic pool. The aim of the present study was to analyze the modifications of the liver bile acid pool during the modulation of liver carcinogenesis by phenobarbital and nafenopin. The animals were submitted to the hepatocarcinogenic initiation-selection (IS) procedure adapted from Solt and Farber. As compared to basal diet, the chronic feeding of phenobarbital significantly increased the total concentrations of liver bile acids both at weeks 9 and 17. That increase was mainly due to a change in the concentration of β-muricholic acid and hyodeoxycholic acid and, to a lesser extent, of chenodeoxycholic acid and α-muricholic acid. In contrast, feeding a diet containing nafenopin led to a significant decrease in the concentration of liver bile acids, due to a complete disappearance of chenodeoxycholic acid and muricholic acid, and a decrease in the concentration of hyodeoxycholic acid. Carcinomas appearing in IS phenobarbital-treated rats contain fewer bile acids than the surrounding parenchyma (because of the decrease in deoxycholic acid and ursodeoxycholic acid) whereas the malignant tumors appearing in IS nafenopin-treated rats have essentially the same pattern of bile acids as the surrounding parenchyma. During modulation of liver carcinogenesis by phenobarbital and nafenopin, changes in bile acid metabolism definitively take place but they are both quantitatively and qualitatively different. Therefore, the perturbations of liver bile acid homeostasis occurring in such a carcinogenic protocol do not seem to be implicated in the positive modulation induced by phenobarbital or nafenopin treatment.

Journal

Archives of Toxicology – Springer Journals

Published: Jun 1, 1994

Keywords: Bile acids; Liver carcinogenesis; Metabolic disorder

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