{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T18:33:38Z","timestamp":1768674818068,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,11,2]],"date-time":"2006-11-02T00:00:00Z","timestamp":1162425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:p>Little is known about the metabolism and mechanism of action of the trypanocide, isometamidium (ISM), the major drug used for prophylaxis of trypanosomiasis. We have investigated its metabolism and distribution in isolated rat hepatocytes using liquid chromatography\u2010mass spectrometry and confocal laser scanning microscopy (CLSM). Two putative metabolites were formed, which were proposed to be a mono\u2010acetyl derivative and an oxidized metabolite (SII). This is the first demonstration of the hepatic metabolism of ISM, as previous <jats:italic>in vivo<\/jats:italic> studies were hampered by dose\u2010limiting toxicity and insensitive analytical methods. The intrinsic fluorescence of the drug enabled its intracellular uptake to be followed by CLSM. It is taken up rapidly into the nucleolus, nuclear membrane and endoplasmic reticulum within 5\u2003min, and retained in the nucleus for at least 24\u2003h. Persistent binding of ISM to cellular macromolecules may contribute to its prophylactic effect <jats:italic>in vivo<\/jats:italic>. Pretreatment of rats with 3\u2010methylcholanthrene, phenobarbitone (PB) or the widely used pyrethroid pesticide, deltamethrin, resulted in an increase in metabolism of ISM to the proposed SII after 1\u2003h incubation with hepatocytes. 3\u2010methylcholanthrene was the most potent inducer, causing a maximal 19.5\u2010fold induction of SII formation after exposure of hepatocytes to ISM for 1\u2003h compared with formation by control hepatocytes. In comparison, at the 1\u2003h timepoint deltamethrin pre\u2010treatment caused a 10.2\u2010fold induction, and PB only 8.2 fold.<\/jats:p>","DOI":"10.1111\/j.1365-2885.2006.00802.x","type":"journal-article","created":{"date-parts":[[2006,11,2]],"date-time":"2006-11-02T23:03:13Z","timestamp":1162508593000},"page":"547-553","source":"Crossref","is-referenced-by-count":3,"title":["Metabolism of isometamidium in hepatocytes isolated from control and inducer\u2010treated rats"],"prefix":"10.1111","volume":"29","author":[{"given":"I.","family":"BOIBESSOT","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. N. A.","family":"TETTEY","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. G.","family":"SKELLERN","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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