Short communicationAffinity of chlordecone and chlordecol for human serum lipoproteins
Introduction
Chlordecone (CLD) is a chlorinated Persistent Organic Pollutant (POP) particularly recalcitrant to biological degradation (Cabidoche et al., 2009; Chaussonnerie et al., 2016; Matolcsy et al., 1988). Its wide use as an insecticide from 1972 to 1993 resulted in high contamination levels of banana plantation soils (Cabidoche et al., 2009; Levillain et al., 2012) which is predicted to last for several centuries (Cabidoche et al., 2009). Comprehensive ecosystem analysis revealed that CLD is one of the most frequently detected chlorinated pesticide in wild birds, reared animals, fishes in nearby contaminated areas or even at the coast (Cavelier, 1980).
In view of this, contamination in humans was inevitable, and impregnation was demonstrated by the Kannari study reporting that more than 90% of the total samples collected from French West Indies population contained mean CLD levels of 1.24 μg.L-1 in Guadeloupe and 1.84 μg.L-1 in Martinique (Dereumeaux and Saoudi, 2018). Epidemiological studies suggest that contamination may have a serious impact on health, including increased incidence of prostate cancer (Multigner et al., 2016) as well as neurodevelopment disorders (Cordier et al., 2015). To evaluate the mode of action of CLD requires a better understanding of its bioavailability in vivo.
It is known that unlike other organochlorine pesticides, CLD concentrations are higher in liver than in fatty tissues in animals (Delannoy et al., 2019). Studies revealed that chlordecol (CLD-OH), a metabolite of CLD, was highly concentrated in the bile, which is also the means by which cholesterol is transported to the intestine for excretion (Soine et al., 1984, 1983). Cholesterol is taken up by the liver in the form of lipoproteins that circulate in the blood, which may also be the means of transport for CLD. Indeed, binding studies using 14C-CLD found that CLD was able to bind to lipoproteins, with a relative distribution of plasma protein ≥ HDL > LDL ≥ VLDL (Soine et al., 1982), suggesting a potential difference of affinity for the different lipoprotein fractions. The objective of this study was to perform real-time analysis of molecular interaction between CLD or CLD-OH and isolated human lipoproteins, LDL and HDL, using switchSENSE® technology.
Section snippets
Preparation of lipoproteins
Lipoproteins from pooled human plasma were prepared by sequential ultracentrifugation (LDL, d1.006 g/mL – d1.063 g/mL, HDL, d1.063- d1.21 g/mL) (Schumaker and Puppione, 1986). Lipoproteins were dialyzed against 40 mM NaCl containing 10 mM Na2HPO4 solution, pH 7.4, stored at 4 °C under N2 before use within 1 week following preparation. Protein concentration was determined using the modified Lowry assay (Markwell et al., 1981). Lipoprotein samples (10 μg protein) were denatured in Laemmli buffer,
Characterization and conjugation of lipoproteins to DNA chip
The purity of the lipoprotein samples was confirmed by the presence of apolipoprotein (apo)B100 in LDL and apoAI in HDL detected by Coomassie Blue staining following separation by SDS-PAGE (Supplementary data 1).
The lipoproteins were covalently conjugated with 48-mer ssDNA and the conjugates were successfully purified by anion-exchange chromatography (Supplementary data, 2).
High frequency dynamic electrical switching mode allowed the measure of hydrodynamic friction to assess absolute size and
Discussion
CLD is metabolized following a 2-step reaction: reduction of CLD to CLD-OH and subsequent conjugation to sulfonide and glucuronide compounds leading to more hydrophilic compounds. The efficiency of each step is highly dependent of the species (Molowa et al., 1986a, 1986b). For humans, previous papers reported amounts between 10 to 58% of conjugated CLD and 2-10% of conjugated CLD-OH (Boylan et al., 1979; Fariss et al., 1980). Overall, the levels of CLD relative to CLD-OH vary within 25% to 75%.
Conclusion
In conclusion, the present study on the affinity of CLD and CLD-OH for LDL and HDL lipoproteins using the switchSENSE® technology provide useful data on the specificity of interaction of CLD with LDL and CLD-OH with HDL, allowing the development of a distribution model of CLD and CLD-OH in human tissues and a better understanding of CLD bioavailabity in humans. These results are a key step for a better understanding of CLD bioavailability.
CRediT authorship contribution statement
Matthieu Delannoy: Writing - original draft, Writing - review & editing, Validation, Investigation, Resources. Jean-Michel Girardet: Writing - original draft, Writing - review & editing, Methodology, Software, Validation, Formal analysis, Investigation, Resources, Data curation, Visualization, Funding acquisition. Fathia Djelti: Writing - original draft. Frances T. Yen: Writing - original draft, Writing - review & editing, Validation, Investigation, Resources. Céline Cakir-Kiefer: Writing -
Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgements
The authors thank Régis Badin and Henri-Joël Affian for lipoprotein preparation. This study received financial support from the scientific research council A2F (University of Lorraine). Biomolecular interactions were investigated with the switchSENSE® technology available at the ASIA platform (University of Lorraine - INRAE; https://a2f.univ-lorraine.fr/asia/).
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Transfer of persistent organic pollutants in food of animal origin – Meta-analysis of published data
2021, ChemosphereCitation Excerpt :The distribution of POPs to organs is realized through blood. Different blood constituents such as lipoproteins (HDL, VLDL, IDL, LDL) and albumins are known to vehicles POPs (Casarett and Doull, 2008; Soine et al., 1982, Delannoy et al., in press). Distribution of these lipophilic POPs result in preferential accumulation of lipophilic POPs in lipid-rich organs.
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Co-senior authors.