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Adult Sprague\u2013Dawley rats treated with acetaminophen or <jats:sc>d<\/jats:sc>\u2010galactosamine (GalN) showed dose\u2010 and time\u2010dependent histomorphological changes and TUNEL staining in liver consistent with hepatocellular necrosis, apoptosis and inflammation up to 72\u00a0h. Matching changes in serum alanine transaminase (ALT), aspartate transaminase (AST) and cyt c peaked at 24\u00a0h for either drug at the highest dose, cyt c falling rapidly at 48\u00a0hours with ALT and AST remained high. Intracellular transit of cyt c from mitochondria to the cytoplasm in damaged hepatocytes, and then to peripheral circulation, was observed by immunohistochemistry. Correlation coefficients between cyt c and serum diagnostic tests indicate the liver to be the primary source of cyt c. Urinary analysis for cyt c revealed time\u2010dependent increase at 6\u00a0h, peaking at 24\u00a0h in GalN\u2010treated rats in contrast with irregular patterns of urinary ALT and AST activity. Histological changes detected at 6\u00a0h preceded altered ALT, AST and cyt c at 12 and 18\u00a0h, respectively, in GalN\u2010treated rats. These studies demonstrate cyt c to be a useful indicator of hepatic injury in rodents and support its utility as a non\u2010invasive predictor of drug\u2010induced hepatotoxicity, when utilized as a potential urinary biomarker. Published in 2008 by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.1347","type":"journal-article","created":{"date-parts":[[2008,4,16]],"date-time":"2008-04-16T12:18:19Z","timestamp":1208348299000},"page":"815-828","source":"Crossref","is-referenced-by-count":34,"title":["Cytochrome c: a non\u2010invasive biomarker of drug\u2010induced liver injury"],"prefix":"10.1002","volume":"28","author":[{"given":"T. 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