{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T10:31:18Z","timestamp":1777717878579,"version":"3.51.4"},"reference-count":17,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2017,8,18]],"date-time":"2017-08-18T00:00:00Z","timestamp":1503014400000},"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":["Int J Toxicol"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>Immunohistochemical staining for the lysosome-associated membrane protein 2 (LAMP-2) has been proposed previously as an alternative to electron microscopy to identify hepatic phospholipidosis. This study used LAMP-2 immunohistochemistry (IHC) to diagnose phospholipidosis in rats exhibiting renal tubular injury. Rats were administered toreforant, a histamine H4 receptor antagonist by oral gavage at a dose of 3, 10, or 100 mg\/kg\/d for 6 months. Hematoxylin and eosin staining revealed renal tubular epithelial cell vacuolation, hypertrophy, degeneration, and luminal dilation in the 100 mg\/kg\/d group animals. Renal tubular injury was confirmed using kidney injury marker 1 (KIM-1) IHC. The involvement of phosopholipidosis in the renal injury was investigated by LAMP-2. Adipophilin IHC was included to differentiate phospholipidosis from lipidosis. Increased LAMP-2 staining was observed in the 100 mg\/kg\/d group animals when compared to vehicle group animals. Lysosome-associated membrane protein-2 staining was most prominent in the outer stripe of the outer medulla where KIM-1 staining was also most prominent. By contrast, adipophilin staining was not increased. Phospholipidosis was also confirmed by electron microscopy. These data support the use of LAMP-2 IHC as a diagnostic tool and suggest an association between phospholipidosis and the renal tubular injury caused by toreforant.<\/jats:p>","DOI":"10.1177\/1091581817726040","type":"journal-article","created":{"date-parts":[[2017,8,18]],"date-time":"2017-08-18T07:24:41Z","timestamp":1503041081000},"page":"386-394","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["An Immunohistochemical Investigation of Renal Phospholipidosis and Toxicity in Rats"],"prefix":"10.1177","volume":"36","author":[{"given":"Jing Ying","family":"Ma","sequence":"first","affiliation":[{"name":"Janssen Research and Development, LLC, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Snook","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, LLC, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheryl","family":"Garrovillo","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, LLC, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Johnson","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, LLC, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"La","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, LLC, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2017,8,18]]},"reference":[{"key":"bibr1-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1177\/153537020122600903"},{"key":"bibr2-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.5.4.567"},{"key":"bibr3-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.08.013"},{"key":"bibr4-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701481956"},{"issue":"2","key":"bibr5-1091581817726040","first-page":"1013","volume":"2","author":"Thurmond RL","year":"2017","journal-title":"Ann Pharmacol Pharm"},{"key":"bibr6-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2008.11.010"},{"key":"bibr7-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.7.4135"},{"key":"bibr8-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00433.x"},{"key":"bibr9-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1623"},{"key":"bibr10-1091581817726040","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-97-6-839"},{"key":"bibr11-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/282540"},{"key":"bibr12-1091581817726040","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-212-44019"},{"issue":"4","key":"bibr13-1091581817726040","first-page":"459","volume":"10","author":"Sun EL","year":"1997","journal-title":"In Vitro Toxicol"},{"issue":"5","key":"bibr14-1091581817726040","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1128\/AAC.43.5.1003","volume":"43","author":"Mineot-Leclercq MP","year":"1999","journal-title":"Antimicrob Agents Chemother"},{"key":"bibr15-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq267"},{"key":"bibr16-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1177\/1091581811430167"},{"key":"bibr17-1091581817726040","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2014.06.014"}],"container-title":["International Journal of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1091581817726040","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1091581817726040","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1091581817726040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:23:39Z","timestamp":1777458219000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1091581817726040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,18]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1177\/1091581817726040"],"URL":"https:\/\/doi.org\/10.1177\/1091581817726040","relation":{},"ISSN":["1091-5818","1092-874X"],"issn-type":[{"value":"1091-5818","type":"print"},{"value":"1092-874X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,18]]}}}