{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T01:01:45Z","timestamp":1787878905462,"version":"build-2784847793"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T00:00:00Z","timestamp":1414454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug\u2010induced QT prolongation has been reported in humans and animals. This potentially lethal effect can be induced by drugs interacting with a cardiac potassium channel, namely hERG (human ether\u2010a go\u2010go\u2010related gene) leading to arrhythmia or <jats:italic>torsade de pointes<\/jats:italic> (TdP). Hence, <jats:italic>in vitro<\/jats:italic> evaluation of therapeutics for their effects on the rapid delayed rectifier current (I<jats:sub>Kr<\/jats:sub>) mediated by the K<jats:sup>+<\/jats:sup> ion channel encoded by hERG is a valuable tool for identifying potential arrhythmic side effects during drug safety testing. Our objective was to evaluate the temperature\u2010induced hERG channel blockade variation by human and veterinary drugs using the IonFlux 16 system. A panel of eight drugs was tested for I<jats:sub>Kr<\/jats:sub> inhibition at both ambient (23\u2009\u00b0C) and physiological (37\u2009\u00b0C) temperatures at various concentrations using IonFlux 16, an automated patch clamp system. Our results established that both amiodarone (IC<jats:sub>50<\/jats:sub>\u2009=\u20090.56\u2009\u03bcM at 23\u2009\u00b0C and 0.30\u2009\u03bcM at 37\u2009\u00b0C) and \u03b2\u2010estradiol (IC<jats:sub>50<\/jats:sub>\u2009=\u200924.72\u2009\u03bcM at 23\u2009\u00b0C and 8.17\u2009\u03bcM at 37\u2009\u00b0C) showed a dose\u2010dependent I<jats:sub>Kr<\/jats:sub> blockade with a higher blockade at 37\u2009\u00b0C. Whereas, blockade of I<jats:sub>Kr<\/jats:sub> by both ivermectin (IC<jats:sub>50<\/jats:sub>\u2009=\u200912.52\u2009\u03bcM at 23\u2009\u00b0C and 24.41\u2009\u03bcM at 37\u2009\u00b0C) and frusemide (IC<jats:sub>50<\/jats:sub>\u2009=\u200912.58\u2009\u03bcM at 23\u2009\u00b0C and 25.55\u2009\u03bcM at 37\u2009\u00b0C) showed a dose\u2010dependent I<jats:sub>Kr<\/jats:sub> blockade with a lower blockade at 37\u2009\u00b0C. Gentamicin, enrofloxacin, xylazine and albendazole did not block I<jats:sub>Kr<\/jats:sub> at both the assessed temperatures. Collectively, these results demonstrate that the effect of temperature variation should be taken into consideration during the evaluation of test drugs for their hERG channel blockade potential. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3074","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T01:37:08Z","timestamp":1414460228000},"page":"799-805","source":"Crossref","is-referenced-by-count":30,"title":["Assessment of temperature\u2010induced hERG channel blockade variation by drugs"],"prefix":"10.1002","volume":"35","author":[{"given":"Rahul R.","family":"Kauthale","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Bombay Veterinary College  Mumbai 400012 Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruta S.","family":"Dadarkar","sequence":"additional","affiliation":[{"name":"Department of Toxicology Piramal Enterprises Limited  Mumbai 400063 Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghib","family":"Husain","sequence":"additional","affiliation":[{"name":"Department of Toxicology Piramal Enterprises Limited  Mumbai 400063 Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas V.","family":"Karande","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Bombay Veterinary College  Mumbai 400012 Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhumanjiri M.","family":"Gatne","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Bombay Veterinary College  Mumbai 400012 Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1975.tb07591.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-011-9360-z"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/08998280.2010.11928628"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1054\/drup.2000.0167"},{"key":"e_1_2_7_6_1","first-page":"1602","article-title":"Pharmacokinetics of intravitreal carbenicillin, cefazolin, and gentamicin in rhesus monkeys","volume":"24","author":"Barza M","year":"1983","journal-title":"Invest. 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