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Species variations in the threshold molecular-weight factor for the biliary excretion of organic anions.

ABSTRACT: 1. The excretion in the bile and urine after intravenous injection of 16 organic anions having molecular weights between 355 and 752 was studied in female rats, guinea pigs and rabbits. 2. These compounds were mostly excreted unchanged, except for three of them, which were metabolized to a slight extent (<7% of dose). 3. The rat excreted all the compounds extensively (22-90% of dose) in the bile. 4. In guinea pigs four of the compounds with mol.wt. 355-403 were excreted in the bile to the extent of 7-16% of the dose, four with mol.wt. 407-465 to the extent of 25-44% and eight compounds with mol.wt. 479-752 to the extent of 44-100%. 5. In rabbits four compounds with mol.wt. 355-465 were excreted in the bile to the extent of 1-8% of the dose, two compounds with mol.wt. 479 and 495 to the extent of 24 and 22%, and six compounds with mol.wt. 505-752 to the extent of 31-94%. 6. These results, together with those of other investigations from this laboratory, are discussed and the conclusion is reached that there is a threshold molecular weight for appreciable biliary excretion (i.e. more than 10% of dose) of anions, which varies with species: about 325+/-50 for the rat, 400+/-50 for the guinea pig and 475+/-50 for the rabbit. 7. Anions with molecular weights greater than about 500 are extensively excreted in the bile of all three species. 8. That proportion of the dose of these compounds which is not excreted in the bile is excreted in the urine, and in the three species, bile and urine are complementary excretory pathways, urinary excretion being greatest for the compounds of lowest molecular weight and tending to decrease with increasing molecular weight. 9. Some implications of this interspecies variation in the molecular-weight requirement for extensive biliary excretion are discussed.

SUBMITTER: Hirom PC

PROVIDER: S-EPMC1174264 | biostudies-other | 1972 Oct

REPOSITORIES: biostudies-other

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Project description:Background and objectivesIdiopathic uric acid nephrolithiasis, which is closely associated with obesity and the metabolic syndrome, is increasing in prevalence. Unduly acidic urine pH, the quintessential pathophysiologic feature of this disease, is in part explained by inadequate excretion of the principal urinary buffer ammonium. The role of net acid excretion in the pathogenesis of uric acid nephrolithiasis is incompletely understood.Design, setting, participants, & measurementsWe compared acid-base parameters of patients with idiopathic uric acid nephrolithiasis with matched control subjects under controlled diets in an inpatient metabolic unit. Measurements included fasting blood and 24-hour urine chemistries and 24-hour urine metabolomic analysis. Comparisons between groups included analysis of covariance models controlling for urine pH or body mass index.ResultsSubjects with idiopathic uric acid nephrolithiasis had lower urine pH (5.5 versus 5.9; P<0.001) and higher net acid excretion (60 versus 43 mEq/24 h; P<0.001), with the excess H+ carried by nonammonium buffers. In all subjects, there was a positive relationship of net acid excretion with higher body mass index in spite of strictly controlled equivalent dietary acid intake. This relationship was most evident among control subjects (r=0.36; P=0.03). It was attenuated in patients with idiopathic uric acid nephrolithiasis whose net acid excretion remained fixedly high and ammonium excretion remained low relative to net acid excretion, resulting in low urine pH over a wide body mass index range. Urinary metabolomics was performed to attempt to identify excess organic acids presented to the kidney in idiopathic uric acid nephrolithiasis. Among the tricarboxylic acid cycle intermediates and amino acid and lipid metabolites analyzed, 26 organic anions with acid dissociation constants values in the range of urine pH showed greater protonation. However, protons carried by the identified organic acids did not entirely account for the higher titratable acidity seen in idiopathic uric acid nephrolithiasis.ConclusionsHigher acid load to the kidney, resulting in higher urinary net acid excretion, is an important factor in the pathogenesis of idiopathic uric acid nephrolithiasis.

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Species variations in the threshold molecular-weight factor for the biliary excretion of organic anions.

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