{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:59:24Z","timestamp":1777913964140,"version":"3.51.4"},"reference-count":42,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"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":[[2016,2]]},"abstract":"<jats:p>\n                    Hepatic macrophages play crucial roles in hepatotoxicity. We investigated immunophenotypes of macrophages in liver injury induced in rats by thioacetamide (TAA; 300 mg\/kg, intraperitoneal) after hepatic macrophage depletion; hepatic macrophages were depleted by liposomal clodronate (CLD; 10 ml\/kg, i.v.) one day before TAA injection. Samples were obtained on post-TAA injection days 0, 1, 2, 3, 5, and 7. TAA injection induced coagulation necrosis of hepatocytes on days 1 through 3 and subsequent reparative fibrosis on days 5 and 7 in the centrilobular area, accompanied by increased numbers of M1 macrophages (expressing cluster of differentiation [CD]68 and major histocompatibility complex class II) and M2 macrophages (expressing CD163 and CD204) mainly on days 1 through 3. TAA + CLD treatment markedly decreased the numbers of M1 and M2 macrophages mainly on days 1 through 3; CD163\n                    <jats:sup>+<\/jats:sup>\n                    Kupffer cells were most sensitive to CLD depletion. In TAA + CLD\u2013treated rats, interestingly, coagulation necrosis of hepatocytes was prolonged with more increased levels of hepatic enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase) to TAA-treated rats; reparative fibrosis was incomplete and replaced by dystrophic calcification in the injured area, indicating the aggravated damage. Furthermore, in TAA + CLD\u2013treated rats, inflammatory factors (monocyte chemoattractant protein [MCP]-1, interferon-\u03b3, tumor necrosis factor-\u03b1, and interleukin-10) and fibrosis-related factors (transforming growth factor-\u03b21, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1) were decreased at messenger RNA levels, indicating abnormal macrophage functions. It was clearly demonstrated that hepatic macrophages have important roles in tissue damage and remodeling in hepatotoxicity.\n                  <\/jats:p>","DOI":"10.1177\/0192623315621191","type":"journal-article","created":{"date-parts":[[2016,3,8]],"date-time":"2016-03-08T07:08:56Z","timestamp":1457420936000},"page":"246-258","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":27,"title":["Depletion of Hepatic Macrophages Aggravates Liver Lesions Induced in Rats by Thioacetamide (TAA)"],"prefix":"10.1177","volume":"44","author":[{"given":"Hossain M.","family":"Golbar","sequence":"first","affiliation":[{"name":"Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Izawa","sequence":"additional","affiliation":[{"name":"Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavindra K.","family":"Wijesundera","sequence":"additional","affiliation":[{"name":"Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Bondoc","sequence":"additional","affiliation":[{"name":"Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anusha H.","family":"Tennakoon","sequence":"additional","affiliation":[{"name":"Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuru","family":"Kuwamura","sequence":"additional","affiliation":[{"name":"Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyoji","family":"Yamate","sequence":"additional","affiliation":[{"name":"Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,3,8]]},"reference":[{"key":"bibr1-0192623315621191","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"bibr2-0192623315621191","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198443"},{"key":"bibr3-0192623315621191","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00430"},{"key":"bibr4-0192623315621191","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2011.9"},{"key":"bibr5-0192623315621191","first-page":"140","volume":"83","author":"Damoiseaux J. 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