{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T22:26:09Z","timestamp":1785191169093,"version":"3.55.0"},"reference-count":38,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T00:00:00Z","timestamp":1537833600000},"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":[[2018,10]]},"abstract":"<jats:p>d-galactosamine (d-GalN) is a well-known hepatotoxic agent that causes liver injury. Conversely, hepatic macrophages play a crucial role in maintaining liver tissue integrity. Macrophage functions were investigated in hepatic lesions induced by a single intraperitoneal injection of d-GalN (800 mg\/kg body weight [BW]) in 6-week-old F344 rats. Blood and liver samples were examined at 8 hr and on 1, 2, 3, and 5 days postsingle injection (PSI). Hepatic lesions consisting of degeneration\/sporadic foci of coagulation necrosis, inflammatory cell reaction, and reparative fibrosis were seen on PSI days 1 and 2, reflected by significantly increased serum levels of aspartate transaminase and alanine transaminase and upregulation of CD68 M1 (tumor necrosis factor-\u03b1, interleukin [IL]-6, and interferon-\u03b3) and CD163 M2 (transforming growth factor-\u03b21, IL-10, monocyte chemoattractant protein-1, and IL-4) macrophage-related factors. Double immunofluorescence staining on PSI day 2 demonstrated that 82% of hepatic macrophages expressed of CD163\/CD68 simultaneously; 65\u201375% of MHC class II macrophages showed co-expression of CD163 or CD68 and 95% CD204-expressing macrophages reacted to CD163 or CD68. These findings showed that both M1- and M2-macrophages contributed to the development of hepatic lesions induced by d-GalN and provided information about macrophage activation, indicating the importance of analysis of macrophage phenotypes for hepatotoxicity based on M1\/M2-polarization.<\/jats:p>","DOI":"10.1177\/0192623318801574","type":"journal-article","created":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T22:45:56Z","timestamp":1537915556000},"page":"764-776","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":40,"title":["M1\/M2-macrophage Polarization-based Hepatotoxicity in\n                    <scp>d<\/scp>\n                    -galactosamine-induced Acute Liver Injury in Rats"],"prefix":"10.1177","volume":"46","author":[{"given":"Nahid","family":"Rahman","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Prefecture University, Izumisano, Osaka, 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