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A simple method to measure sulfonation in man using paracetamol as probe drug.

ABSTRACT: Sulfotransferase enzymes (SULT) catalyse sulfoconjugation of drugs, as well as endogenous mediators, gut microbiota metabolites and environmental xenobiotics. To address the limited evidence on sulfonation activity from clinical research, we developed a clinical metabolic phenotyping method using paracetamol as a probe substrate. Our aim was to estimate sulfonation capability of phenolic compounds and study its intraindividual variability in man. A total of 36 healthy adult volunteers (12 men, 12 women and 12 women on oral contraceptives) received paracetamol in a 1 g-tablet formulation on three separate occasions. Paracetamol and its metabolites were measured in plasma and spot urine samples using liquid chromatography-high resolution mass spectrometry. A metabolic ratio (Paracetamol Sulfonation Index-PSI) was used to estimate phenol SULT activity. PSI showed low intraindividual variability, with a good correlation between values in plasma and spot urine samples. Urinary PSI was independent of factors not related to SULT activity, such as urine pH or eGFR. Gender and oral contraceptive intake had no impact on PSI. Our SULT phenotyping method is a simple non-invasive procedure requiring urine spot samples, using the safe and convenient drug paracetamol as a probe substrate, and with low intraindividual coefficient of variation. Although it will not give us mechanistic information, it will provide us an empirical measure of an individual's sulfonator status. To the best of our knowledge, our method provides the first standardised in vivo empirical measure of an individual's phenol sulfonation capability and of its intraindividual variability. EUDRA-CT 2016-001395-29, NCT03182595 June 9, 2017.

SUBMITTER: Marto N

PROVIDER: S-EPMC8079418 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The critical micelle concentration (CMC) is an important parameter of widely used surfactants and needs to be measured in the application and development of surfactants. Fluorometric method is a widely used method determining CMC values owing to the advantages of highly sensitivity, fast response and wide application range. There are two common methods (I and II) of preparing samples for CMC fluorometric determination. In the process of developing CMC probes with aggregation-induced emission (AIE) characteristics, we found that methods I and II were not suitable for CMC probes with AIE charateristics and developed a new sample preparation method (III), which is not only suitable for CMC probes with AIE characteristic but also decreases operation procedures and errors owing to omitting the addition of micro amount of dyes into each sample. To ascertain if method III is also suitable for other CMC probes without AIE characteristics, the CMC values of surfactants were determined by fluorometric method using widely used pyrene without AIE charateristic as probe and methods I-III to prepare samples. The obtained experimental results proved that method III not only was suitable for preparation of samples for CMC determination of surfactants using pyrene as probe but also led to the least average deviation (methods I-III led to ±0.13, ±0.34 and ±0.05 mM deviation for the CMC determination of sodium dodecyl sulfate (SDS), respectively). The CMC determination using pyrene as probe is based on its change in the ratio (I FIII/I FI) of its emission peaks I and III with surfactant concentration. Unexpectedly, it was found that the I FIII/I FI value of pyrene in surfactant solutions is sensitive to the measurement conditions changing exciting light energy, such as slit widths and sample-measured number. In addition, it was found that surfactant SDS or cetrimonium bromide from different suppliers not only has significantly different CMC values but also leads to very different I FIII/I FI values of pyrene in a certain concentration of surfactant, which can be used as a simple method to distinguish the same surfactant with different CMC values.

Project description:Background: As costs decline, the size and scope of microarray experiments have increased. In multi-centre studies there is a need to ensure consistency of data pre-processing across centres. Similarly, in smaller scale studies the evolution of microarray platforms means that there is often a need to compare data generated on earlier microarrays to that generated on newer ones. It is important in such studies to ensure that platform-dependent biases are removed so that meta-analysis of different datasets can be performed reliably. In both these cases the optimal scenario is to have a small subset of samples repeated at each site or on each platform. These replicates can then be used to learn a relationship between probe intensities on the two platforms. Results: I introduce here a simple, linear-modelling-based method for normalizing data from multiple-platforms by using replicate hybridizations. A dataset of 20 rat liver samples is used as a benchmark. Eight samples are hybridized to two separate versions of Affymetrix microarrays, while the other 12 are hybridized to one, for a total of 28 arrays. Our linear modelling method removes platform bias as assessed using both unsupervised machine-learning and two-group statistical analyses. The method is computationally efficient and works well for data pre-processed by the GCRMA, RMA and MAS5 algorithms and using either default or alternative probe-mappings. The method is very stable towards the number of replicate samples used, with even two replicates greatly reducing platform-specific bias. Conclusions: A simple linear-modelling method can remove platform-specific bias independent of the pre-processing algorithm and ProbeSet-mapping used. This technique can readily be extended to multi-site experiments, and suggests the benefits of including a small number of replicate hybridizations in each new study as a normalization control. Twenty rats livers were processed, eight on both RAE230-A and RAE230-2 arrays, 8 on only RAE230-A arrays, and 4 on RAE230-2 arrays only.

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A simple method to measure sulfonation in man using paracetamol as probe drug.

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