title: Circulating microRNAs in drug safety assessment for hepatic and cardiovascular toxicity: the latest biomarker frontier?
abstract: Drug-induced liver and cardiovascular injuries are important aspects of safety evaluations of numerous drugs in development. Therefore, reliable and predictive biomarkers to allow detection of early signs of drug-induced liver and cardiovascular injuries are required in clinical and preclinical pharmaceutical evaluation. MicroRNAs (miRNAs) are reported to be present in body fluids (blood, urine, etc.), and these 'circulating miRNAs' have been proposed as toxicological biomarkers of drug-induced tissue injury in preclinical and clinical practice. To be used as biomarkers of drug toxicity, such miRNAs need to show rapid and injured-tissue-specific upregulation in body fluids after injury, be more sensitive than existing protein markers such as alanine aminotransferase (ALT) and troponins, and be able to identify the toxicants responsible, if possible. In this article, we focus on the current knowledge of circulating miRNAs, which have potential for use in assessment of drug-induced liver and cardiovascular injuries. In addition, we discuss an important question regarding normalization of the expression levels of certain circulating miRNAs in body fluids.
authors.affiliation: Division of Pathological Biochemistry, Department of Biomedical Sciences, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan, osamitsu@med.tottori-u.ac.jp.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Osaki
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kosaka
authors.forename: Futoshi
authors.initials: F
authors.lastname: Okada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000139:chemically induced*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood; D006801:Humans; D035683:MicroRNAs / Q000097:blood*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs