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1.
Toxicol Lett ; 348: 85-96, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34044057

ABSTRACT

The skin epidermis is continuously exposed to external aggressions, including environmental pollution. The cosmetic industry must be able to offer dedicated products to fight the effects of pollutants on the skin. We set up an experimental model that exposed skin explants maintained in culture to a pollutant mixture. This mixture P representing urban pollution was designed on the basis of the French organization 'Air Parif' database. A chamber, called Pollubox®, was built to allow a controlled nebulization of P on the cultured human skin explants. We investigated ultrastructural morphology by transmission electron microscopy of high pressure frozen skin explants. A global transcriptomic analysis indicated that the pollutant mixture was able to induce relevant xenobiotic and antioxidant responses. Modulated detoxifying genes were further investigated by laser micro-dissection coupled to qPCR, and immunochemistry. Both approaches showed that P exposure correlated with overexpression of detoxifying genes and provoked skin physiological alterations down to the stratum basale. The model developed herein might be an efficient tool to study the effects of pollutants on skin as well as a powerful testing method to evaluate the efficacy of cosmetic products against pollution.


Subject(s)
Air Pollutants/toxicity , Environmental Pollution/adverse effects , Skin/drug effects , Humans , Microscopy, Electron, Transmission , Receptors, Aryl Hydrocarbon/physiology , Skin/metabolism , Skin/pathology , Skin/ultrastructure , Xenobiotics/toxicity
2.
Toxicology ; 248(2-3): 151-7, 2008 Jun 27.
Article in English | MEDLINE | ID: mdl-18450356

ABSTRACT

Organophosphorus chemical warfare agents (nerve agents) are to be feared in military operations as well as in terrorist attacks. Among them, VX (O-ethyl-S-[2-(diisopropylamino)ethyl] methylphosphonothioate) is a low volatility liquid that represents a percutaneous as well as an inhalation hazard if aerosolized. It is a potent irreversible cholinesterase (ChE) inhibitor that causes severe signs and symptoms, including respiratory dysfunction that stems from different mechanisms. VX-induced pulmonary oedema was previously reported in dogs but mechanisms involved are not well understood, and its clinical significance remains to be assessed. An experimental model was thus developed to study VX-induced cardiovascular changes and pulmonary oedema in isoflurane-anaesthetized swine. In the course of this study, we observed a fast and unexpected rebound of plasma ChE activity following inhibition provoked by the intravenous injection of 6 and 12 microg kg(-1) of VX. In whole blood ChE activity, the rebound could stay unnoticed. Further investigations showed that the rebound of plasma esterase activity was neither related to spontaneous reactivation of ChE nor to VX-induced increase in paraoxonase/carboxylesterase activities. A bias in Ellman assay, haemoconcentration or severe liver cytolysis were also ruled out. All in all, these results suggest that the rebound was likely due to the release of butyrylcholinesterase into the blood stream from ChE producing organs. Nature of the organ(s) and mechanisms involved in enzyme release will need further investigations as it may represent a mechanism of defence, i.e. VX scavenging, that could advantageously be exploited.


Subject(s)
Chemical Warfare Agents/toxicity , Cholinesterase Inhibitors/toxicity , Cholinesterases/blood , Organothiophosphorus Compounds/toxicity , Animals , Butyrylcholinesterase/blood , Dose-Response Relationship, Drug , Injections, Intravenous , Male , Pulmonary Edema/chemically induced , Pulmonary Edema/metabolism , Pulmonary Edema/pathology , Swine
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