Biomolecules & Therapeutics  
Circulating Plasma and Exosomal microRNAs as Indicators of Drug-Induced Organ Injury in Rodent Models
Young-Eun Cho1,4, Sang-Hyun Kim2, Byung-Heon Lee3 and Moon-Chang Baek1,*
Departments of 1Molecular Medicine, 2Pharmacology, 3Biochemistry and Cell Biology, CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea, 4Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA
E-mail: mcbaek@knu.ac.kr
Tel: +82-53-420-4948, Fax: +82-53-420-4944
Received: August 4, 2016; Revised: November 4, 2016; Accepted: December 13, 2016; Published online: February 17, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant N-acetyl-cysteine. Circulating miR-146a and miR-206 were increased in cisplatin-induced nephrotoxicity and bupivacaine-induced myotoxicity, respectively. Taken together, these results indicate that circulating plasma and exosomal miRNAs can be used as potential biomarkers specific for drug-induced liver, kidney or muscle injury.
Keywords: miRNAs, Exosomes, Liver-specific injury, N-acetyl cysteine, Biomarkers


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