A systems biology approach to understanding elevated serum alanine transaminase levels in a clinical trial with ximelagatran

作者：Andersson Ulf^*; Lindberg Johan; Wang Shunghuang; Balasubramanian Raji; Marcusson Stahl Maritha; Hannula Mira; Zeng Chenhui; Juhasz Peter J; Kolmert Johan; Backstrom Jonas; Nord Lars; Nilsson Kerstin; Martin Steve; Glinghammar Bjorn; Cederbrant Karin; Schuppe Koistinen Ina

来源：Biomarkers, 2009, 14(8): 572-586.

DOI：10.3109/13547500903261354

• Liver injury
• systems biology
• alanine aminotransferase
• pyruvate
• ximelagatran

Ximelagatran was developed for the prevention and treatment of thromboembolic conditions. However, in long-term clinical trials with ximelagatran, the liver injury marker, alanine aminotransferase (ALT) increased in some patients. Analysis of plasma samples from 134 patients was carried out using proteomic and metabolomic platforms, with the aim of finding predictive biomarkers to explain the ALT elevation. Analytes that were changed after ximelagatran treatment included 3-hydroxybutyrate, pyruvic acid, CSF1R, Gc-globulin, L-glutamine, protein S and alanine, etc. Two of these analytes (pyruvic acid and CSF1R) were studied further in human cell cultures in vitro with ximelagatran. A systems biology approach applied in this study proved to be successful in generating new hypotheses for an unknown mechanism of toxicity.

• 出版日期2009