Journal Article

Detection of Cell-Free, Liver-Specific mRNAs in Peripheral Blood from Rats with Hepatotoxicity: A Potential Toxicological Biomarker for Safety Evaluation

Makoto Miyamoto, Mariko Yanai, Shingo Ookubo, Naoko Awasaki, Kenji Takami and Ryoetsu Imai

in Toxicological Sciences

Volume 106, issue 2, pages 538-545
Published in print December 2008 | ISSN: 1096-6080
Published online September 2008 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfn188
Detection of Cell-Free, Liver-Specific mRNAs in Peripheral Blood from Rats with Hepatotoxicity: A Potential Toxicological Biomarker for Safety Evaluation

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To verify the concept that cell-free organ/tissue–specific mRNAs leaking from drug-damaged organs/tissues into peripheral blood could be toxicological biomarkers for identification of the target organs of drug toxicity, we attempted to detect liver-specific mRNAs in peripheral blood from rats with chemical-induced hepatotoxicity. We selected α1-microglobulin/bikunin precursor (Ambp) and albumin mRNAs as tentative liver-specific biomarkers and successfully detected them by reverse transcription (RT)-PCR in peripheral blood 24 h after D-galactosamine HCl (D-gal) or acetaminophen administration. Moreover, albumin mRNA was detected 2 h after D-gal administration, although plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were still unchanged. On the other hand, in peripheral blood from rat with bupivacaine HCl–induced skeletal muscle damage, neither Ambp nor albumin mRNA was detectable while plasma creatine kinase, ALT, and AST levels prominently increased 2 or 12 h after dosing. Furthermore, Ambp mRNA was also detectable in filtered plasma from rats with liver damage, indicating that cell-free Ambp mRNA can be present in peripheral blood. In conclusion, cell-free, liver-specific Ambp, and albumin mRNAs were detectable in peripheral blood from rats with chemical-induced liver damage. It is believed that the detection of cell-free organ/tissue–specific mRNA in peripheral blood is a promising approach in the survey of toxicological biomarkers.

Keywords: biomarker; cell free; hepatotoxicity; liver-specific mRNA; peripheral blood; rat

Journal Article.  4373 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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