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<datestamp>2017-12-21</datestamp>
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<title lang=en>Inhibition of organic anion transporter (OAT) activity by cigarette smoke condensate</title>
<creator>Sayyed, Katia</creator>
<creator>Le Vee, Marc</creator>
<creator>Abdel-Razzak, Ziad</creator>
<creator>Fardel, Olivier</creator>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Lebanese University [Beirut]</contributor>
<contributor>CHU Pontchaillou [Rennes]</contributor>
<contributor>We thank Dr. Yannick Parmentier and Dr. Claire Denizot for helpful support with HEK293 cell clones overexpressing transporters. Katia Sayyed was supported by a grant from AZM Association-UL (Tripoli, Lebanon).</contributor>
<description>International audience</description>
<source>ISSN: 0887-2333</source>
<source>Toxicology in Vitro</source>
<publisher>Elsevier</publisher>
<identifier>hal-01579604</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579604</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579604/document</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579604/file/Sayyed%20et%20al.%20-%20Inhibition%20of%20organic%20anion%20transporter%20%28OAT%29%20acti.pdf</identifier>
<source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579604</source>
<source>Toxicology in Vitro, Elsevier, 2017, 44, pp.27-35. 〈10.1016/j.tiv.2017.06.014〉</source>
<identifier>DOI : 10.1016/j.tiv.2017.06.014</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1016/j.tiv.2017.06.014</relation>
<identifier>PUBMED : 28629854</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/28629854</relation>
<language>en</language>
<subject lang=en>Cigarette Smoke</subject>
<subject lang=en> Drug transporter</subject>
<subject lang=en> Heterocyclic amines</subject>
<subject lang=en> Organic anion transporter</subject>
<subject lang=en> pharmacokinetics</subject>
<subject>[SDV.TOX] Life Sciences [q-bio]/Toxicology</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Cigarette smoke condensate (CSC) has previously been shown to impair activity and expression of hepatic drug transporters. In the present study, we provided evidence that CSC also hinders activity of organic anion transporters (OATs), notably expressed at the kidney level. CSC thus cis-inhibited OAT substrate uptake in OAT1- and OAT3-transfected HEK293 cells, in a concentration-dependent manner (IC50=72.1μg/mL for OAT1 inhibition and IC50=27.3μg/mL for OAT3 inhibition). By contrast, OAT4 as well as the renal organic cation transporter (OCT) 2 were less sensitive to the inhibitory effect of CSC (IC50=351.5μg/mL and IC50=226.2μg/mL, for inhibition of OAT4 and OCT2, respectively). OAT3 activity was further demonstrated to be blocked by some single chemicals present in cigarette smoke such as the heterocyclic amines AαC (IC50=11.3μM) and PhIP (IC50=1.9μM), whereas other major cigarette smoke components used at 100μM, like nicotine, the nitrosamine NNK and the polycyclic aromatic hydrocarbons benzo(a)pyrene and phenanthrene, were without effect. AαC and PhIP however failed to trans-stimulate activity of OAT3, suggesting that they were not substrates for this transporter. Taken together, these data establish OAT1 and OAT3 transporters as targets of cigarette smoke chemicals, which may contribute to smoking-associated pharmacokinetics alterations.</description>
<date>2017</date>
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