Graduate School of Biomedical Sciences, MS in Clinical Investigation Program
Theses, UMMS; MicroRNAs; Acetaminophen
Pharmacology, Toxicology and Environmental Health
To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice.
Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters.
We distinguished numerous, unique plasma miRNAs both up- and down-regulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and down-regulated miRNAs, included, but were not limited to, 574-5p, 466g, 466f-3p, 375, 29c, and 148a. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point ( P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point ( P = 0.011).
We identified unique plasma miRNAs both up- and down-regulated in lethally dosed APAP poisoned mice.
Ward, Jeanine, "MicroRNA Markers of Acetaminophen Toxicity: A Master's Thesis" (2012). University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 625.