{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T04:48:20Z","timestamp":1777265300745,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,7,21]],"date-time":"2016-07-21T00:00:00Z","timestamp":1469059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS079249, NS072097, ES007148, AR055073, ES005022"],"award-info":[{"award-number":["NS079249, NS072097, ES007148, AR055073, ES005022"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>Accidental or intentional exposures to parathion, an organophosphorus (OP) pesticide, can cause severe poisoning in humans. Parathion toxicity is dependent on its metabolism by the cytochrome P450 (CYP) system to paraoxon (diethyl 4\u2010nitrophenyl phosphate), a highly poisonous nerve agent and potent inhibitor of acetylcholinesterase. We have been investigating inhibitors of CYP\u2010mediated bioactivation of OPs as a method of preventing or reversing progressive parathion toxicity. It is well recognized that NADPH\u2013cytochrome P450 reductase, an enzyme required for the transfer of electrons to CYPs, mediates chemical redox cycling. In this process, the enzyme diverts electrons from CYPs to support chemical redox cycling, which results in inhibition of CYP\u2010mediated biotransformation. Using menadione as the redox\u2010cycling chemical, we discovered that this enzymatic reaction blocks metabolic activation of parathion in rat and human liver microsomes and in recombinant CYPs important to parathion metabolism, including CYP1A2, CYP2B6, and CYP3A4. Administration of menadione to rats reduces metabolism of parathion, as well as parathion\u2010induced inhibition of brain cholinesterase activity. This resulted in inhibition of parathion neurotoxicity. Menadione has relatively low toxicity and is approved by the Food and Drug Administration for other indications. Its ability to block parathion metabolism makes it an attractive therapeutic candidate to mitigate parathion\u2010induced neurotoxicity.<\/jats:p>","DOI":"10.1111\/nyas.13156","type":"journal-article","created":{"date-parts":[[2016,7,21]],"date-time":"2016-07-21T19:18:59Z","timestamp":1469128739000},"page":"80-86","source":"Crossref","is-referenced-by-count":24,"title":["Novel approaches to mitigating parathion toxicity: targeting cytochrome P450\u2013mediated metabolism with menadione"],"prefix":"10.1111","volume":"1378","author":[{"given":"Yi\u2010Hua","family":"Jan","sequence":"first","affiliation":[{"name":"Department of Environmental and Occupational Health Rutgers University School of Public Health Piscataway New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason R.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeast Ohio Medical University Rootstown Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela A.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health Rutgers University School of Public Health Piscataway New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Mishin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Rutgers University Ernest Mario School of Pharmacy Piscataway New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane E.","family":"Heck","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Science New York Medical College Valhalla New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra L.","family":"Laskin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Rutgers University Ernest Mario School of Pharmacy Piscataway New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey D.","family":"Laskin","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health Rutgers University School of Public Health Piscataway New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(93)90066-M"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.emc.2014.09.010"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-032305260-3.50050-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.1991.tb112852.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/138955706776073510"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)90733-J"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.21519"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm200054r"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2012.10.020"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2010.02.023"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu205"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2005.02.025"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(97)00180-9"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802612803989219"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2013.06.012"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2015.01.007"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/S0022-3565(25)26712-X","article-title":"Studies on the effect of chlorcyclizine and other drugs on the toxicity of several organophosphate anticholinesterases","volume":"143","author":"Welch R.M.","year":"1964","journal-title":"J. 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