{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:55:35Z","timestamp":1792083335394,"version":"4.4.0"},"reference-count":20,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T00:00:00Z","timestamp":1233446400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:p>Recently, it was reported that the intraperitoneal administration of 30 mg\/kg\/day troglitazone to heterozygous superoxide dismutase 2 gene knockout (Sod2+\/\u2212) mice for twenty-eight days caused liver injury, manifested by increased serum ALT activity and hepatic necrosis. Therefore, we evaluated the reproducibility of troglitazone-induced liver injury in Sod2+\/\u2212 mice, as well as their validity as an animal model with higher sensitivity to mitochondrial toxicity by single-dose treatment with acetaminophen in Sod2+\/\u2212 mice. Although we conducted a repeated dose toxicity study in Sod2+\/\u2212 mice treated orally with 300 mg\/kg\/day troglitazone for twenty-eight days, no hepatocellular necrosis was observed in our study. On the other hand, six hours and twenty-four hours after an administration of 300 mg\/kg acetaminophen, plasma ALT activity was significantly increased in Sod2+\/\u2212 mice, compared to wild-type mice. In particular, six hours after administration, hepatic centrilobular necrosis was observed only in Sod2+\/\u2212 mice. These results suggest that Sod2+\/\u2212 mice are valuable as an animal model with higher sensitivity to mitochondrial toxicity. On the other hand, it was suggested that the mitochondrial damage alone might not be the major cause of the troglitazone-induced idiosyncratic liver injury observed in humans.<\/jats:p>","DOI":"10.1177\/0192623308329282","type":"journal-article","created":{"date-parts":[[2009,3,30]],"date-time":"2009-03-30T16:22:07Z","timestamp":1238430127000},"page":"193-200","source":"Crossref","is-referenced-by-count":90,"title":["Sensitivity of Liver Injury in Heterozygous\n                    <i>Sod2<\/i>\n                    Knockout Mice Treated with Troglitazone or Acetaminophen"],"prefix":"10.1177","volume":"37","author":[{"given":"Kazunori","family":"Fujimoto","sequence":"first","affiliation":[{"name":"Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Shizuoka, Japan"},{"name":"Graduate School of Bioagricultural Sciences, Nagoya University, Aichi, 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