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Updated: May 21, 2026
Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: a research study
Jeanine Ward1, Shashi Bala, Jan Petrasek
1Department of Emergency Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, United States.
Aim:
To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice.
Methods:
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.
Results:
We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5 p, 466 g, 466 f-3p, 375, 29 c, and 148 a, have been shown to be associated with asthma in prior studies. Interestingly, a relationship between APAP and asthma has been previously well described in the literature, with an as yet unknown mechanism of pathology. 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).
Conclusion:
We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.
Insights
Researchers identified unique plasma microRNA (miRNA) profiles linked to acetaminophen (APAP) poisoning in mice. These specific miRNAs are also associated with asthma development, suggesting a potential connection between APAP toxicity and respiratory conditions.
Area of Science:
- Biochemistry
- Toxicology
- Genetics
Background:
- Acetaminophen (APAP) overdose is a leading cause of acute liver failure.
- The precise mechanisms linking APAP toxicity to other conditions like asthma remain unclear.
- Plasma microRNAs (miRNAs) are emerging as potential biomarkers for various disease states.
Purpose of the Study:
- To identify specific plasma miRNA signatures associated with lethal acetaminophen toxicity in a murine model.
- To compare miRNA profiles between lethal and sublethal APAP dosing to pinpoint toxicity-specific markers.
Main Methods:
- Plasma samples were collected from mice subjected to lethal (500 mg/kg) or sublethal (150 mg/kg) acetaminophen doses.
- Commercially available murine miRNA libraries were utilized for comprehensive screening.
- Differential expression analysis was performed to identify unique miRNA profiles between dosing groups.
Main Results:
- Numerous unique plasma miRNAs were found to be differentially expressed (up- and downregulated) in mice with lethal APAP toxicity compared to sublethal doses.
- Several identified miRNAs, including miR-574-5p, miR-466g, miR-466f-3p, miR-375, miR-29c, and miR-148a, have prior associations with asthma.
- Lethal APAP dosing led to significantly elevated alanine aminotransferase levels and a 90% mortality rate within 48 hours.
Conclusions:
- Distinct plasma miRNA profiles are associated with acetaminophen-induced hepatotoxicity.
- The identified miRNAs correlate with asthma development, suggesting a potential molecular link between APAP poisoning and respiratory pathology.
