{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:37:37Z","timestamp":1786631857153,"version":"build-2736575974"},"reference-count":42,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":2695,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Trichloroacetic acid, an oxidative metabolite of trichloroethylene (TRI), is a ligand of the peroxisome proliferator-activated receptor \u03b1 (PPAR) \u03b1, which is involved in lipid homeostasis and anti-inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We examined the role of mouse and human PPAR\u03b1 in TRI-induced hepatic steatosis and toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male wild-type (mPPAR\u03b1), Ppar\u03b1-null, and humanized PPAR\u03b1 (hPPAR\u03b1) mice on an Sv\/129 background were exposed via inhalation to 0, 1,000, and 2,000 ppm TRI for 8 hr\/day for 7 days. We assessed TRI-induced steatosis or hepatic damage through biochemical and histopathological measurements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Plasma alanine aminotransferase and aspartate aminotransferase activities increased in all mouse lines after exposure to 1,000 and 2,000 ppm TRI. Exposure induced hepatocyte necrosis and inflammatory cells in all mouse lines, but hepatic lipid accumulation was observed only in Ppar\u03b1-null and hPPAR\u03b1 mice. No differences were observed in TRI-mediated induction of hepatic PPAR\u03b1 target genes except for a few genes that differed between mPPAR\u03b1 and hPPAR\u03b1 mice. However, TRI significantly increased expression of triglyceride (TG)-synthesizing enzymes, diacylglicerol acyltransferases, and PPAR\u03b3 in Ppar\u03b1-null and hPPAR\u03b1 mice, which may account for the increased TG in their livers. TRI exposure elevated nuclear factor-kappa B (NF\u03baB) p52 mRNA and protein in all mice regardless of PPAR\u03b1 genotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NF\u03baB-p52 is a candidate molecular marker for inflammation caused by TRI, and PPAR\u03b1 may be involved in TRI-induced hepatosteatosis. However, human PPAR\u03b1 may afford only weak protection against TRI-mediated effects compared with mouse PPAR\u03b1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1289\/ehp.1001928","type":"journal-article","created":{"date-parts":[[2010,8,13]],"date-time":"2010-08-13T11:21:15Z","timestamp":1281698475000},"page":"1557-1563","source":"Crossref","is-referenced-by-count":34,"title":["Differential Response to Trichloroethylene-Induced Hepatosteatosis in Wild-Type and PPAR\u03b1-Humanized Mice"],"prefix":"10.1021","volume":"118","author":[{"given":"Doni Hikmat","family":"Ramdhan","sequence":"first","affiliation":[{"name":"Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michihiro","family":"Kamijima","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan"},{"name":"Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan"},{"name":"Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisao","family":"Naito","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Nagoya University Graduate 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