Influence of obesity on sulfonamide disposition in Zucker rats

Kaul, Sushma; Ritschel, W. A.

doi:10.1007/bf03190091

Cited by 4 publications

(3 citation statements)

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“…Both the femoral artery and vein were catheterized in order to obtain samples and to administer the test compound, respectively. A single bolus of BSP (1.26 mg/kg bodyweight) or SA (4.23 mg/kg bodyweight) was administered (these doses do not saturate the transport systems; therefore, the kinetics can be adequately estimated 11,13,14 ). Blood samples were collected at 0–8 min for BSP and 0–45 min for SA from the femoral artery cannula (using a heparinized syringe).…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics Of Organic Anions In Rats With Arterial Calcinosis

Quaglia

Hofer

Torres

2002

Clin Exp Pharmacol Physiol

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1. Ageing induces calcium accumulation in the vascular system. The simplest experimental way of producing high degrees of arterial calcium overload is by administration of an overdose of vitamin D(3) to rats. The aim of the present study was to evaluate the pharmacokinetics of organic anions in rats with arterial calcinosis induced by an overdose of vitamin D(3). 2. We used bromosulfophthalein (BSP) and sulfanilamide (SA) as models of organic anions with preferential biliary and renal excretion, respectively. 3. Increases in the clearance and elimination rate constant of BSP were observed in treated rats. The clearance and the elimination rate constant for SA were also increased in rats with arterial calcinosis. 4. Variations in arterial hepatic blood flow, aspartate aminotransferase activity and liver calcium accumulation were not observed in treated rats. In contrast, treated rats had a lower renal blood flow and increased renal calcium levels. 5. In summary, rats with arterial calcinosis showed an increase in total body clearance of both BSP and SA, probably associated with modifications in their metabolism and/or in organ extraction. Alterations to hepatic and renal blood flow do not account for these phenomena.

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Section: Methodsmentioning

confidence: 99%

Pharmacokinetics Of Organic Anions In Rats With Arterial Calcinosis

Quaglia

Hofer

Torres

2002

Clin Exp Pharmacol Physiol

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“…Pharmacokinetic studies Blood concentration-time data following intravenous administration of the sulfonamides were taken from our previous report (29) for the calculation of phannacokinetic parameters. In the experiments, 6 groups of female lean Zucker rats (6 animals/group), with a mean weight range of 220-343 g, were cannulated via the right jugular vein.…”

Section: Extent Of Protein Bindingmentioning

confidence: 99%

Quantitative structure — pharmacokinetic relationship of a series of sulfonamides in the rat

Kaul

Ritschel

1990

Eur. J. Drug Metab. Pharmacokinet.

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The pharmacokinetics of a series of sulfonamides were investigated after intravenous administration of a 7 mg/kg dose of individual sulfonamides to cannulated female lean Zucker rats. The concentrations of the sulfonamides in blood were determined by colorimetry. The blood concentration-time curves were fitted to a biexponential equation. The partition coefficient, log P, and pKa values of the sulfonamides were taken from the literature, log P and pKa values differed markedly across the series. The extent of protein binding varied enormously, increasing with partition coefficient. There was no significant relationship between the volume of distribution and partition coefficient. However, when the influence of protein binding on volume of distribution was eliminated, a significant linear relationship emerged. Total clearance formed a relatively complex nonlinear relationship with partition coefficient. The relationship of elimination half-life and partition coefficient was inverse of that between clearance and partition coefficient because of a lack of significant relationship between volume of distribution and partition coefficient.

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“…Inhibition of CAVA has been identified as a novel anti-obesity strategy, over the other because of their serious cardiovascular or central nervous system (CNS) side effects. Several studies have provided insight that inhibition of CAVA with sulfonamide/sulfamate drug has potential as anti-obesity (Kaul and Ritschel 1988 ). However, better inhibitors are needed to overcome the problem of selectivity, since CAVA share a close homology, with other CA isoform, to design selective inhibitors of CAVA is challenging (Iqbal et al 2015 ; Swenson 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Cloning, expression, purification and characterization of human mitochondrial carbonic anhydrase VA

et al. 2016

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Carbonic anhydrase VA (CAVA) is a mitochondrial enzyme that catalyzes the reversible hydration of CO2 to produce HCO3 − and proton. CAV is primarily involved in several biosynthetic processes such as ureagenesis, gluconeogenesis and lipogenesis by providing bicarbonate ion. Here, we report a new strategy for cloning, expression and purification for CAVA in the bacterial system followed by its biophysical characterization. The cDNA of CAVA, a 801 nucleotide long that encodes a 267-amino acid polypeptide of molecular mass of 30-kDa (excluding signal peptide), was sub-cloned in the expression vector pET21c and transformed into Escherichia coli strain BL21 (DE3) for expression. The recombinant protein was purified in two steps by Ni–NTA and DEAE weak anion-exchange chromatography under native condition from the supernatant, while inclusion bodies (IBs) were used to get protein under the denatured condition with a relatively high yield. CAVA was purified under denatured conditions in a single step using Ni–NTA chromatography. SDS-PAGE showed a band of 30-kDa, which was further confirmed as CAVA by Western blot and MALDI-TOF/MS. We further performed enzyme activity to ensure that both forms of purified proteins are enzymatically active. Measurements of secondary structure of the native, denatured and renatured proteins were carried out using circular dichroism. The purified protein can be further used for structural and biochemical studies.

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Influence of obesity on sulfonamide disposition in Zucker rats

Cited by 4 publications

References 50 publications

Pharmacokinetics Of Organic Anions In Rats With Arterial Calcinosis

Pharmacokinetics Of Organic Anions In Rats With Arterial Calcinosis

Quantitative structure — pharmacokinetic relationship of a series of sulfonamides in the rat

Cloning, expression, purification and characterization of human mitochondrial carbonic anhydrase VA

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