{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:57:35Z","timestamp":1791824255153,"version":"4.3.4"},"reference-count":38,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2012,1,30]],"date-time":"2012-01-30T00:00:00Z","timestamp":1327881600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p>To provide mechanistic insight in the induction of phospholipidosis and the appearance of the proposed biomarker di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP), rats were treated with 150 mg\/kg amiodarone for 12 consecutive days and analyzed at three different time points (day 4, 9, and 12). Biochemical analysis of the serum revealed a significant increase in cholesterol and phospholipids at the three time points. Bio-analysis on the serum and urine detected a time-dependent increase in BMP, as high as 10-fold compared to vehicle-treated animals on day 12. Paralleling these increases, micro-array analysis on the liver of treated rats identified cholesterol biosynthesis and glycerophospholipid metabolism as highly modulated pathways. This modulation indicates that during phospholipidosis-induction interactions take place between the cationic amphiphilic drug and phospholipids at the level of BMP-rich internal membranes of endosomes, impeding cholesterol sorting and leading to an accumulation of internal membranes, converting into multilamellar bodies. This process shows analogy to Niemann-Pick disease type C (NPC). Whereas the NPC-induced lipid traffic jam is situated at the cholesterol sorting proteins NPC1 and NPC2, the amiodarone-induced traffic jam is thought to be located at the BMP level, demonstrating its role in the mechanism of phospholipidosis-induction and its significance for use as a biomarker.<\/jats:p>","DOI":"10.1177\/0192623311432290","type":"journal-article","created":{"date-parts":[[2012,1,31]],"date-time":"2012-01-31T03:18:07Z","timestamp":1327979887000},"page":"491-503","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":46,"title":["Phospholipidosis in Rats Treated with Amiodarone: Serum Biochemistry and Whole Genome Micro-Array Analysis Supporting the Lipid Traffic Jam Hypothesis and the Subsequent Rise of the Biomarker BMP"],"prefix":"10.1177","volume":"40","author":[{"given":"Natalie","family":"Mesens","sequence":"first","affiliation":[{"name":"Genetic and Exploratory Toxicology, Drug Safety Sciences, Janssen Pharmaceutical Companies of Johnson & Johnson, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miek","family":"Desmidt","sequence":"additional","affiliation":[{"name":"Genetic and Exploratory Toxicology, Drug Safety Sciences, Janssen Pharmaceutical Companies of Johnson & Johnson, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert R.","family":"Verheyen","sequence":"additional","affiliation":[{"name":"Genetic and Exploratory Toxicology, Drug Safety Sciences, Janssen Pharmaceutical Companies of Johnson & Johnson, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie","family":"Starckx","sequence":"additional","affiliation":[{"name":"Genetic and Exploratory Toxicology, Drug Safety Sciences, Janssen Pharmaceutical Companies of Johnson & Johnson, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegrid","family":"Damsch","sequence":"additional","affiliation":[{"name":"Genetic and Exploratory Toxicology, Drug Safety Sciences, Janssen Pharmaceutical Companies of Johnson & Johnson, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald De","family":"Vries","sequence":"additional","affiliation":[{"name":"Genetic and Exploratory Toxicology, Drug Safety Sciences, Janssen Pharmaceutical Companies of Johnson & Johnson, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Verhemeldonck","sequence":"additional","affiliation":[{"name":"Genetic and Exploratory Toxicology, Drug Safety Sciences, Janssen Pharmaceutical Companies of Johnson & Johnson, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacky Van","family":"Gompel","sequence":"additional","affiliation":[{"name":"Genetic and Exploratory Toxicology, Drug Safety Sciences, Janssen Pharmaceutical Companies of Johnson & Johnson, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Lampo","sequence":"additional","affiliation":[{"name":"Genetic and Exploratory Toxicology, Drug Safety Sciences, Janssen Pharmaceutical Companies of Johnson & Johnson, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieve","family":"Lammens","sequence":"additional","affiliation":[{"name":"Genetic and Exploratory Toxicology, Drug Safety Sciences, Janssen Pharmaceutical Companies of Johnson & Johnson, 2340 Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,1,30]]},"reference":[{"key":"bibr1-0192623311432290","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M003822"},{"key":"bibr2-0192623311432290","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2006.10.015"},{"key":"bibr3-0192623311432290","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M600488-JLR200"},{"key":"bibr4-0192623311432290","doi-asserted-by":"publisher","DOI":"10.1177\/0192623309352496"},{"key":"bibr5-0192623311432290","unstructured":"De Duve C. 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