PMID- 28796322 OWN - NLM STAT- MEDLINE DCOM- 20181022 LR - 20181022 IS - 1552-8618 (Electronic) IS - 0730-7268 (Linking) VI - 37 IP - 1 DP - 2018 Jan TI - Ecotoxicological properties of ketoprofen and the S(+)-enantiomer (dexketoprofen): Bioassays in freshwater model species and biomarkers in fish PLHC-1 cell line. PG - 201-212 LID - 10.1002/etc.3943 [doi] AB - The increased use of nonsteroidal anti-inflammatory drugs (NSAIDs) has resulted in their ubiquitous presence in the environment. The toxicological properties of these 2 widely prescribed NSAIDs, namely racemic ketoprofen and its enantiomer S(+)-ketoprofen (dexketoprofen), were evaluated, firstly, by acute and chronic toxicity tests using 3 representative model organisms (Vibrio fischeri, Pseudokirchneriella subcapitata, and Ceriodaphnia dubia) and, secondly, by evaluating the responses of biotransformation systems and multidrug resistance-associated proteins (MRP1/MRP2) using the Poeciliopsis lucida hepatocellular carcinoma 1 (PLHC-1) fish hepatic cell line. Toxicity data from both acute and chronic dexketoprofen exposure indicated higher sensitivity through inhibition of bioluminescence and algal growth and through increased mortality/immobilization compared to racemic ketoprofen exposure. The growth inhibition test showed that racemic ketoprofen and dexketoprofen exhibited different effect concentration values (240.2 and 65.6 mug/L, respectively). Furthermore, racemic ketoprofen and dexketoprofen did not exert cytotoxic effects in PLHC-1 cells and produced compound-, time-, and concentration-specific differential effects on cytochrome P450 1A (CYP1A) and glutathione S-transferase levels. For CYP1A, the effects of racemic ketoprofen and dexketoprofen differed at the transcriptional and catalytic levels. Exposure to racemic ketoprofen and dexketoprofen modulated MRP1 and MRP2 mRNA levels, and these effects were also dependent on compound, exposure time, and concentration of the individual drug. The present study revealed for the first time the interactions between these NSAIDs and key detoxification systems and different sensitivity to the racemic mixture compared to its enantiomer. Environ Toxicol Chem 2018;37:201-212. (c) 2017 SETAC. CI - (c) 2017 SETAC. FAU - Mennillo, Elvira AU - Mennillo E AD - Department of Veterinary Sciences, University of Pisa, San Piero a Grado, Italy. FAU - Arukwe, Augustine AU - Arukwe A AD - Department of Biology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. FAU - Monni, Gianfranca AU - Monni G AD - Department of Veterinary Sciences, University of Pisa, San Piero a Grado, Italy. FAU - Meucci, Valentina AU - Meucci V AD - Department of Veterinary Sciences, University of Pisa, San Piero a Grado, Italy. FAU - Intorre, Luigi AU - Intorre L AD - Department of Veterinary Sciences, University of Pisa, San Piero a Grado, Italy. FAU - Pretti, Carlo AU - Pretti C AD - Department of Veterinary Sciences, University of Pisa, San Piero a Grado, Italy. AD - Interuniversity Center of Marine Biology (CIBM) "G. Bacci," Livorno, Italy. LA - eng PT - Journal Article DEP - 20171011 PL - United States TA - Environ Toxicol Chem JT - Environmental toxicology and chemistry JID - 8308958 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Biomarkers) RN - 0 (Multidrug Resistance-Associated Proteins) RN - 0 (RNA, Messenger) RN - 90Y4QC304K (Ketoprofen) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A1) RN - EC 2.5.1.18 (Glutathione Transferase) SB - IM MH - Aliivibrio fischeri/physiology MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/toxicity MH - Biological Assay/*methods MH - Biomarkers/*metabolism MH - Biotransformation/drug effects MH - Cell Line MH - Cyprinodontiformes/growth & development/*metabolism MH - Cytochrome P-450 CYP1A1/genetics/metabolism MH - *Ecotoxicology MH - *Fresh Water MH - Glutathione Transferase/metabolism MH - Ketoprofen/*chemistry/*toxicity MH - Luminescence MH - Multidrug Resistance-Associated Proteins/metabolism MH - RNA, Messenger/genetics/metabolism MH - Reproduction/drug effects MH - Stereoisomerism MH - Survival Analysis MH - Toxicity Tests, Acute MH - Toxicity Tests, Chronic OTO - NOTNLM OT - Bioassay OT - Biomarker OT - Ecotoxicology OT - Nonsteroidal anti-inflammatory drug OT - PLHC-1 cell OT - Pharmaceutical EDAT- 2017/08/11 06:00 MHDA- 2018/10/23 06:00 CRDT- 2017/08/11 06:00 PHST- 2017/02/02 00:00 [received] PHST- 2017/04/21 00:00 [revised] PHST- 2017/08/08 00:00 [accepted] PHST- 2017/08/11 06:00 [pubmed] PHST- 2018/10/23 06:00 [medline] PHST- 2017/08/11 06:00 [entrez] AID - 10.1002/etc.3943 [doi] PST - ppublish SO - Environ Toxicol Chem. 2018 Jan;37(1):201-212. doi: 10.1002/etc.3943. Epub 2017 Oct 11.