Hepatic drug transport in the rat

Blom, Anton; Scaf, A. H. J.; Meijer, Dirk K. F.

doi:10.1016/0006-2952(82)90380-x

Cited by 53 publications

(1 citation statement)

References 34 publications

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“…Studies in vivo have usually involved extraction of trapped adducts from liver tissue following administration of the toxin, and while those studies are important in identifying the type(s) of radical generated in the intact animal, attempts at correlating free radical production and damage have been limited to the more versatile systems in vitro (Tomasi et al, 1983;Cheeseman et al, 1985). Although extrapolation ofdata obtained in vitro to the whole animal has been achieved, this is often fraught with difficulties; indeed, there are numerous examples where isolated cells do not mimic the whole organ, let alone the situation in vivo (Blom et al, 1982;Miller et al, 1983;Hughes, 1989;Powell et al, 1989). Thus information on the amount and rate of production of free radicals in the whole animal or the intact liver is lacking.…”

Section: Introductionmentioning

confidence: 99%

The role of the liver in the production of free radicals during halothane anaesthesia in the rat. Quantification of N-tert-butyl-alpha-(4-nitrophenyl)nitrone (PBN)-trapped adducts in bile from halothane as compared with carbon tetrachloride

Hughes

George

Evans

et al. 1991

Biochemical Journal

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Halothane or CCl4 was co-administered with the spin trap N-tert-butyl-alpha-(4-nitrophenyl)nitrone (PBN) to rats fitted with bile duct cannuli or to isolated perfused liver preparations. Rats maintained under halothane anaesthesia generated significant amounts of free radicals, and 5-9 nmol was excreted in bile over 1 h. No adducts were detected in urine or plasma. The hepatic origin of these free radicals was confirmed by studies on isolated perfused livers where the addition of halothane to the perfusate resulted in the biliary elimination of the same PBN-trapped radical adducts. Similarly, following CCl4 administration, the same radical species were eliminated in bile in the whole animal and the perfused liver preparation. In the perfused liver, over 3 h the total biliary elimination of radicals derived from halothane or CCl4 (administered at equimolar concentrations) was approximately the same (5-7 nmol); however, the elimination of halothane-derived radicals was more rapid over the first 1 h.

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Section: Introductionmentioning

confidence: 99%

The role of the liver in the production of free radicals during halothane anaesthesia in the rat. Quantification of N-tert-butyl-alpha-(4-nitrophenyl)nitrone (PBN)-trapped adducts in bile from halothane as compared with carbon tetrachloride

Hughes

George

Evans

et al. 1991

Biochemical Journal

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Transport and Metabolism in the Hepatobiliary System

Meijer

1989

Comprehensive Physiology

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Selective hepatobiliary transport defect for organic anions and neutral steroids in mutant rats with hereditary-conjugated hyperbilirubinemia

et al. 1987

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Mutant rats (TM rats) with abnormal hepatic excretory function were used to study biliary transport of dibromosulfophthalein, ouabain, tributylmethyl ammonium, cholate and taurocholate. In whole animals, dibromosulfophthalein and ouabain clearance is reduced to 7 and 37% of normal, respectively, due to severely impaired excretion from liver to bile. Initial uptake rates of these agents are relatively little affected. In the isolated perfused liver preparation, dibromosulfophthalein is retained within liver and perfusion medium, and the 60-min recovery on bile is reduced to 1.5 vs 75% in normal controls. Biliary excretion of cholate, taurocholate and the quaternary ammonium cation, [14C]tributylmethyl ammonium, is not impaired. These results provide evidence for a selective defect of organic anion and neutral steroid transport in TM rats and confirm that multiple pathways exist for the hepatobiliary excretion of organic anions, neutral steroids, bile acids and cations. Bile flow in whole animals and in the isolated perfused liver is reduced to 50 and 30% of normal, respectively. This suggests that a normal function of the excretory systems for organic anions and neutral steroids is important for the maintenance of normal bile flow.

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Hepatic drug transport in the rat

Cited by 53 publications

References 34 publications

The role of the liver in the production of free radicals during halothane anaesthesia in the rat. Quantification of N-tert-butyl-alpha-(4-nitrophenyl)nitrone (PBN)-trapped adducts in bile from halothane as compared with carbon tetrachloride

The role of the liver in the production of free radicals during halothane anaesthesia in the rat. Quantification of N-tert-butyl-alpha-(4-nitrophenyl)nitrone (PBN)-trapped adducts in bile from halothane as compared with carbon tetrachloride

Transport and Metabolism in the Hepatobiliary System

Selective hepatobiliary transport defect for organic anions and neutral steroids in mutant rats with hereditary-conjugated hyperbilirubinemia

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