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Our previous studies have shown that acetyl <jats:sc>l<\/jats:sc>\u2010carnitine (ALCAR) prevents cardiotoxicity and developmental toxicity induced by verapamil, a CCB used to treat patients with hypertension. Here, we tested whether toxicities of nifedipine, a dihydropyridine CCB used to treat hypertension, can also be mitigated by co\u2010treatment with ALCAR. In the zebrafish embryos at three different developmental stages, nifedipine induced developmental toxicity with pericardial sac edema in a dose\u2010dependent manner, which were surprisingly exacerbated with ALCAR co\u2010treatment. Even with low\u2010dose nifedipine (5\u00a0\u03bc<jats:sc>m<\/jats:sc>), when the pericardial sac looked normal, ALCAR co\u2010treatment showed pericardial sac edema. We hypothesized that toxicity by nifedipine, a vasodilator, may be prevented by ketamine, a known vasoconstrictor. Nifedipine toxicity in the embryos was effectively prevented by co\u2010treatment with low (subanesthetic) doses (25\u2010100\u00a0\u03bc<jats:sc>m<\/jats:sc> added to the water) of ketamine, although a high dose of ketamine (2\u00a0m<jats:sc>m<\/jats:sc> added to the water) partially prevented the toxicity.As expected of a CCB, nifedipine either in the presence or absence of ketamine\u2010reduced metabolic reactive oxygen species (ROS), a downstream product of calcium signaling, in the rapidly developing digestive system. However, nifedipine induced ROS in the trunk region that showed significantly stunted growth indicating that the tissues under stress potentially produced pathologic ROS. To the best of our knowledge, these studies for the first time show that nifedipine and the dietary supplement ALCAR together induce adverse effects while providing evidence on the therapeutic efficacy of subanesthetic doses of ketamine against nifedipine toxicity in vivo.<\/jats:p>","DOI":"10.1002\/jat.3901","type":"journal-article","created":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T22:40:21Z","timestamp":1570660821000},"page":"257-269","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nifedipine toxicity is exacerbated by acetyl <scp>l<\/scp>\u2010carnitine but alleviated by low\u2010dose ketamine in zebrafish in vivo"],"prefix":"10.1002","volume":"40","author":[{"given":"Bonnie L.","family":"Robinson","sequence":"first","affiliation":[{"name":"Division of Neurotoxicology US Food and Drug Administration  Jefferson Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2606-0461","authenticated-orcid":false,"given":"Qiang","family":"Gu","sequence":"additional","affiliation":[{"name":"Division of Neurotoxicology US Food and Drug Administration  Jefferson Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volodymyr","family":"Tryndyak","sequence":"additional","affiliation":[{"name":"Division of Biochemical Toxicology, National Center for Toxicological Research US Food and Drug Administration  Jefferson Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4896-8075","authenticated-orcid":false,"given":"Syed F.","family":"Ali","sequence":"additional","affiliation":[{"name":"Division of Neurotoxicology US Food and Drug Administration  Jefferson Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Dumas","sequence":"additional","affiliation":[{"name":"The Bionetics Corporation  Jefferson Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0283-9729","authenticated-orcid":false,"given":"Jyotshna","family":"Kanungo","sequence":"additional","affiliation":[{"name":"Division of Neurotoxicology US Food and Drug Administration  Jefferson Arkansas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.09.009"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/PEC.0b013e3181b0a504"},{"issue":"2","key":"e_1_2_6_4_1","first-page":"276","article-title":"Comparative effects of bepridil, diltiazem, nifedipine and verapamil on haemodynamic parameters and myocardial oxygen consumption in anaesthetized dogs","volume":"284","author":"Beaughard M.","year":"1986","journal-title":"Archives Internationales de Pharmocodynamie et de Th\u00e9rapie"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/ajem.2000.9264"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.3.1215"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.2478\/jtim-2018-0029"},{"issue":"3","key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/S0026-895X(24)05633-5","article-title":"2,3,7,8\u2010Tetrachlorodibenzo\u2010p\u2010dioxin activation of the aryl hydrocarbon receptor\/aryl hydrocarbon receptor nuclear translocator pathway causes developmental toxicity through a CYP1A\u2010independent mechanism in zebrafish","volume":"66","author":"Carney S. 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