Hepatic uptake and metabolism of benzoate: a multiple indicator dilution, perfused rat liver study

Multiple, noneliminated references ((51)Cr-labeled erythrocytes, (125)I-albumin, [(14)C]- or [(3)H]sucrose, and [(2)H](2)O), together with [(3)H]hippurate or [(14)C]benzoate, were injected simultaneously into the portal vein of the perfused rat liver during single-pass delivery of benzoate (5-1,000...

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Bibliographic Details
Published in:American journal of physiology: Gastrointestinal and liver physiology 2001-06, Vol.280 (6), p.G1124-G1136
Main Authors: Schwab, A J, Tao, L, Yoshimura, T, Simard, A, Barker, F, Pang, K S
Format: Article
Language:English
Subjects:
Animals
Benzoates - metabolism
Benzoates - pharmacokinetics
Glycine - metabolism
Hippurates - metabolism
In Vitro Techniques
Indicator Dilution Techniques
Kinetics
Liver - metabolism
Male
Models, Biological
Perfusion
Rats
Rats, Sprague-Dawley
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Summary:Multiple, noneliminated references ((51)Cr-labeled erythrocytes, (125)I-albumin, [(14)C]- or [(3)H]sucrose, and [(2)H](2)O), together with [(3)H]hippurate or [(14)C]benzoate, were injected simultaneously into the portal vein of the perfused rat liver during single-pass delivery of benzoate (5-1,000 microM) and hippurate (5 microM) to investigate hippurate formation kinetics and transport. The outflow dilution data best fit a space-distributed model comprising vascular and cellular pools for benzoate and hippurate; there was further need to segregate the cellular pool of benzoate into shallow (cytosolic) and deep (mitochondrial) pools. Fitted values of the membrane permeability-surface area products for sinusoidal entry of unbound benzoate were fast and concentration independent (0.89 +/- 0.17 ml. s(-1). g(-1)) and greatly exceeded the plasma flow rate (0.0169 +/- 0.0018 ml. s(-1). g(-1)), whereas both the influx of benzoate into the deep pool and the formation of hippurate occurring therein appeared to be saturable. Results of the fit to the dilution data suggest rapid uptake of benzoate, with glycination occurring within the deep and not the shallow pool as the rate-determining step.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.2001.280.6.g1124