Plasma Concentration of 36 (Poly)phenols and Prospective Body Weight Change in Participants from the EPIC Cohort.

INTRODUCTION: Dietary intake of (poly)phenols has been linked to reduced adiposity and body weight (BW) in several epidemiological studies. However, epidemiological evidence on (poly)phenol biomarkers, particularly plasma concentrations, is scarce. We aimed to investigate the associations between plasma (poly)phenols and prospective BW change in participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: This study included 761 participants with data on BW at baseline and after 5 years of follow-up. Plasma concentrations of 36 (poly)phenols were measured at baseline using liquid chromatography-tandem mass spectrometry. Associations were assessed through general linear mixed models and multinomial logistic regression models, using change in BW as a continuous or as a categorical variable (BW loss, maintenance, gain), respectively. Plasma (poly)phenols were assessed as log2-transformed continuous variables. The false discovery rate (FDR) was used to control for multiple comparisons. RESULTS: Doubling plasma (poly)phenol concentrations showed a borderline trend towards a positive association with BW loss. Plasma vanillic acid showed the strongest association (-0.53 kg/5 years; 95% confidence interval [CI]: -0.99, -0.07). Similar results were observed for plasma naringenin comparing BW loss versus BW maintenance (odds ratio: 1.1; 95% CI: 1.0, 1.2). These results did not remain significant after FDR correction. CONCLUSION: Higher concentrations of plasma (poly)phenols suggested a tendency towards 5-year BW maintenance or loss. While certain associations seemed promising, they did not withstand FDR correction, indicating the need for caution in interpreting these results. Further studies using (poly)phenol biomarkers are needed to confirm these suggestive protective trends.

Study of the Distribution of Acetaminophen and Its Metabolites in Rats, from the Whole-Body to Isolated Organ Levels, by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging after On-Tissue Chemical Derivatization.

During drug development, detailed investigations of the pharmacokinetic profile of the drug are required to characterize its absorption, distribution, metabolism, and excretion properties. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is an established technique for studies of the distribution of drugs and their metabolites. It has advantages over autoradiography, which is conventionally used for distribution studies: it does not require the radiolabeling of drugs and can distinguish between the drug and its metabolites directly in the tissue. However, its lack of sensitivity in certain cases remains challenging. Novel procedures, such as on-tissue chemical derivatization (OTCD), could be developed to increase sensitivity. We used OTCD to enhance the sensitivity of MALDI-MSI for one of the most widely used drugs, acetaminophen, and to study its distribution in tissues. Without derivatization, this drug and some of its metabolites are undetectable by MALDI-MSI in the tissues of treated rats. We used 2-fluoro-1-methylpyridinium p-toluene sulfonate as a derivatization reagent, to increase the ionization yield of acetaminophen and some of its metabolites. The OTCD protocol made it possible to study the distribution of acetaminophen and its metabolites in whole-body sections at a spatial resolution of 400 µm and in complex anatomical structures, such as the testis and epididymis, at a spatial resolution <50 µm. The OTCD is also shown to be compatible with the quantification of acetaminophen by MALDI-MSI in whole-body tissues. This protocol could be applied to other molecules bearing phenol groups and presenting a low ionization efficiency.

On-tissue chemical derivatization reagents for matrix-assisted laser desorption/ionization mass spectrometry imaging.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a key tool for the analysis of biological tissues. It provides spatial and quantitative information about different types of analytes within tissue sections. Despite the increasing improvements of this technique, the low detection sensitivity of some compounds remains an important challenge to overcome. Poor sensitivity is related to weak ionization efficiency, low abundance of analytes and matrix ions, or endogenous interferences. On-tissue chemical derivatization (OTCD) has proven to be an important solution to these issues and is increasingly employed in MALDI MSI studies. OTCD reagents, synthesized or commercially available, have been essentially used for the detection of small exogenous or endogenous molecules within tissues. Optimally, an OTCD reaction is performed in mild conditions, in an acceptable range of time, preserves the integrity of the tissues, and prevents the delocalization. In addition to their reactivity with a targeted chemical function, some OTCD reagents can also be used as a matrix, which simplifies the sample preparation procedure. In this review, we present an exhaustive overview of OTCD reagents and methods used in MALDI MSI studies.