Determination of total and conjugated glucuronic acid in serum and urine employing a modified naphthoresorcinol reagent

Mazzuchin, A.; Walton, R. J.; Thibert, R.J.

doi:10.1016/0006-2944(71)90082-2

Cited by 13 publications

(2 citation statements)

References 24 publications

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“…Mouse chow was analyzed for ascorbate in the same manner as tissue samples. Glucuronic acid in urine was measured as described previously (45). Collagen synthesis was measured using Masson and picrosirius red staining in multiple sections from each of 5 Slc23a1 +/+ and 5 Slc23a1 -/-newborn pups (46).…”

Section: Methodsmentioning

confidence: 99%

Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice

et al. 2010

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Levels of the necessary nutrient vitamin C (ascorbate) are tightly regulated by intestinal absorption, tissue accumulation, and renal reabsorption and excretion. Ascorbate levels are controlled in part by regulation of transport through at least 2 sodium-dependent transporters: Slc23a1 and Slc23a2 (also known as Svct1 and Svct2, respectively). Previous work indicates that Slc23a2 is essential for viability in mice, but the roles of Slc23a1 for viability and in adult physiology have not been determined. To investigate the contributions of Slc23a1 to plasma and tissue ascorbate concentrations in vivo, we generated Slc23a1 -/-mice. Compared with wild-type mice, Slc23a1 -/-mice increased ascorbate fractional excretion up to 18-fold. Hepatic portal ascorbate accumulation was nearly abolished, whereas intestinal absorption was marginally affected. Both heterozygous and knockout pups born to Slc23a1 -/-dams exhibited approximately 45% perinatal mortality, and this was associated with lower plasma ascorbate concentrations in dams and pups. Perinatal mortality of Slc23a1 -/-pups born to Slc23a1 -/-dams was prevented by ascorbate supplementation during pregnancy. Taken together, these data indicate that ascorbate provided by the dam influenced perinatal survival. Although Slc23a1 -/-mice lost as much as 70% of their ascorbate body stores in urine daily, we observed an unanticipated compensatory increase in ascorbate synthesis. These findings indicate a key role for Slc23a1 in renal ascorbate absorption and perinatal survival and reveal regulation of vitamin C biosynthesis in mice.

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Section: Methodsmentioning

confidence: 99%

Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice

et al. 2010

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“…On the basis of the retention times of other modified peptides, a corresponding AG-glycated peptide would have eluted earlier still from the cation exchange column, suggesting that detection of the unique glucuronylated species was not a result of in-source fragmentation of an AG-glycated precursor ion. This seemingly novel adduct is attributed tentatively to a somewhat rare, nonenzymic, posttranslational modification occurring in vivo by the slow reaction of HSA with glucuronic acid in plasma (Mazzuchin et al, 1971;Smith et al, 1990). In a separate study using similar analytical methods, we found glucosylated Lys525 (Barnaby et al, 2011) in vivo (data not shown).…”

Section: Circulating Protein Adducts In Diclofenac Patientsmentioning

confidence: 99%

Mass Spectrometric Characterization of Circulating Covalent Protein Adducts Derived from a Drug Acyl Glucuronide Metabolite: Multiple Albumin Adductions in Diclofenac Patients

Hammond

Meng

Jenkins

et al. 2014

J Pharmacol Exp Ther

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Covalent protein modifications by electrophilic acyl glucuronide (AG) metabolites are hypothetical causes of hypersensitivity reactions associated with certain carboxylate drugs. The complex rearrangements and reactivities of drug AG have been defined in great detail, and protein adducts of carboxylate drugs, such as diclofenac, have been found in liver and plasma of experimental animals and humans. However, in the absence of definitive molecular characterization, and specifically, identification of signature glycation conjugates retaining the glucuronyl and carboxyl residues, it cannot be assumed any of these adducts is derived uniquely or even fractionally from AG metabolites. We have therefore undertaken targeted mass spectrometric analyses of human serum albumin (HSA) isolated from diclofenac patients to characterize drug-derived structures and, thereby, for the first time, have deconstructed conclusively the pathways of adduct formation from a drug AG and its isomeric rearrangement products in vivo. These analyses were informed by a thorough understanding of the reactions of HSA with diclofenac AG in vitro. HSA from six patients without drug-related hypersensitivities had either a single drug-derived adduct or one of five combinations of 2-8 adducts from among seven diclofenac N-acylations and three AG glycations on seven of the protein's 59 lysines. Only acylations were found in every patient. We present evidence that HSA modifications by diclofenac in vivo are complicated and variable, that at least a fraction of these modifications are derived from the drug's AG metabolite, and that albumin adduction is not inevitably a causation of hypersensitivity to carboxylate drugs or a coincidental association.

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Preclinical pharmacology of the anthrapyrazole analog oxantrazole (NSC-349174, Piroxantrone)

Frank

Mathiesen

Szurszewski

et al. 1989

Cancer Chemother. Pharmacol.

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Oxantrazole (now designated as piroxantrone) is an anthrapyrazole analog under evaluation as a potentially useful anthracycline-like antitumor agent. In preparation for phase I clinical trials, we characterized certain aspects of oxantrazole preclinical pharmacology, including plasma stability, murine pharmacokinetics, in vitro/in vivo metabolism, and DNA damage following incubation with human tumor cells in culture. Oxantrazole was relatively unstable in fresh mouse and dog plasma and particularly unstable in fresh human plasma (t 1/2 less than 5 min at 37 degrees C). Its decomposition in plasma was prevented by the addition of ascorbic acid, suggesting oxidative degradation. Following rapid i.v. administration of oxantrazole to mice, plasma elimination was best described by a two-compartment open model with an elimination-phase half-life, total body clearance, and steady-state volume of distribution of 330 min, 458 ml/min per m2, and 87.9 l/m2, respectively. The c x t value calculated following i.v. administration of 90 mg/m2 oxantrazole to mice was 177 micrograms-min/ml. This value was subsequently used in a pharmacologically guided dose-escalation scheme for the oxantrazole phase I clinical trial. Oxantrazole was converted to a polar conjugate, presumably a beta-glucuronide, by rat but not mouse hepatic microsomal preparations and in vivo by the mouse. Oxantrazole introduced protein-associated DNA strand breaks following incubation with a human rhabdomyosarcoma cell line. Repair of the damage was complete by 15 h. Clinical pharmacologic studies are currently under way in conjunction with the phase I clinical trial of oxantrazole.

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Determination of total and conjugated glucuronic acid in serum and urine employing a modified naphthoresorcinol reagent

Cited by 13 publications

References 24 publications

Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice

Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice

Mass Spectrometric Characterization of Circulating Covalent Protein Adducts Derived from a Drug Acyl Glucuronide Metabolite: Multiple Albumin Adductions in Diclofenac Patients

Preclinical pharmacology of the anthrapyrazole analog oxantrazole (NSC-349174, Piroxantrone)

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