{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T05:57:00Z","timestamp":1769579820506,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug\u2010induced phospholipidosis (DIPL) is characterized by phospholipid storage in the lysosomes of affected tissues. Many severe effects and toxicities have been linked to DIPL. The aim of this study was to determine whether the endogenous opioid system is involved in chloroquine\u2010induced phospholipidosis. The effect of naltrexone as an antagonist of opioid receptors in chloroquine\u2010induced phospholipidosis in rat liver was investigated by morphological, biochemical, and molecular modelling studies. Transmission electron microscopy (TEM) showed that morphological characteristic changes of rat liver, including the number of lamellar bodies, grade of vacuolization and cell steatosis, were markedly attenuated in rats treated with naltrexone alone or in combination with chloroquine, in comparison with chloroquine\u2010treated rats. The results of liquid chromatography mass spectrometry (LC\/MS) showed that the concentrations of phenylacetylglycine (PAG) and hippuric acid (HA) were significantly decreased and increased, respectively, in target groups. Besides, the concentration ratio of PAG\/HA was significantly decreased. Spectrophotometry resulted in a notable decrease in alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities in target groups. The results from the molecular docking and molecular dynamic simulation studies demonstrated clear chloroquine interaction with the active site cavity of the \u00b5\u00a0opioid receptor. These data suggest that administration of naltrexone alone, or in combination with chloroquine, notably attenuates the side effects of chloroquine\u2010induced phospholipidosis, as well as demonstrating an increased probability of the endogenous opioid system involvement in chloroquine\u2010induced phospholipidosis in rat liver.<\/jats:p>","DOI":"10.1111\/1440-1681.13332","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T05:59:25Z","timestamp":1588658365000},"page":"1575-1583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigating the role of endogenous opioid system in chloroquine\u2010induced phospholipidosis in rat liver by morphological, biochemical and molecular modelling studies"],"prefix":"10.1111","volume":"47","author":[{"given":"Mohammad Reza","family":"Malek","sequence":"first","affiliation":[{"name":"Department of Biochemistry Institute of Biochemistry and Biophysics (IBB) University of Tehran  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3436-465X","authenticated-orcid":false,"given":"Shahin","family":"Ahmadian","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Institute of Biochemistry and Biophysics (IBB) University of Tehran  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8001-5565","authenticated-orcid":false,"given":"Ahmad Reza","family":"Dehpour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8993-4859","authenticated-orcid":false,"given":"Azadeh","family":"Ebrahim\u2010Habibi","sequence":"additional","affiliation":[{"name":"Biosensor Research Center, Endocrinology and Metabolism Molecular\u2010Cellular Sciences Institute Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahshid","family":"Shafizadeh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Institute of Biochemistry and Biophysics (IBB) University of Tehran  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaheh","family":"Kashani\u2010Amin","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.08.013"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.08.061"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1293\/tox.21.9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etp.2009.07.007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-4-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp200641e"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"5190","DOI":"10.1016\/S0021-9258(19)70769-8","article-title":"Inhibition of lysosomal phospholipase A and phospholipase C by chloroquine and 4, 4'\u2010bis (diethylaminoethoxy) a, pdiethyldiphenylethane","volume":"255","author":"Matsuzawa Y","year":"1980","journal-title":"J Biol Chem"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2003.36"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.225"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b14-00297"},{"key":"e_1_2_7_12_1","first-page":"5","article-title":"Opioid system modulates the immune function: a review","volume":"1","author":"Liang X","year":"2016","journal-title":"Transl Perioper Pain Med"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(99)00221-X"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.076778"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12279"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2013.2046"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/13547500400018570"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/1354750X.2016.1252958"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7250"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.107.123190"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2004.02347.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2015.04.016"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2015.11.020"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.2174\/138945012799201612"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318238bba6"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200316750"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M073395"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092673"},{"key":"e_1_2_7_29_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0021-9258(18)89718-6","article-title":"Chloroquine\u2010induced phospholipid fatty liver","volume":"260","author":"Hostetler KY","year":"1985","journal-title":"J Biol Chem"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1159\/000485886"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135998"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68010344.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2011.08.003"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu426"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.23899"}],"container-title":["Clinical and Experimental Pharmacology and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1440-1681.13332","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.13332","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1440-1681.13332","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.13332","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T17:15:09Z","timestamp":1693934109000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1440-1681.13332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,25]]},"references-count":35,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1111\/1440-1681.13332"],"URL":"https:\/\/doi.org\/10.1111\/1440-1681.13332","archive":["Portico"],"relation":{},"ISSN":["0305-1870","1440-1681"],"issn-type":[{"value":"0305-1870","type":"print"},{"value":"1440-1681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,25]]},"assertion":[{"value":"2020-01-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}