摘要
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 574-5p, 466g, 466f-3p, 375, 29c, and 148a, 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.
AIM： To investigate plasma microRNA （miRNA） profiles indicative of hepatotoxicity in the setting of lethal acet- aminophen （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 mi- croRNA 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 com- pared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5p, 466g, 466f-3p, 375, 29c, and 148a, 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 sub- lethal APAP dosing groups at the 12 h time point （P 〈 0.001）. There was 90% mortality in the lethally com- pared 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.
基金
Supported by PHS grant DK075635 to Szabo G and McNeil Consumer Healthcare, a division of McNeil-PCC Inc. to Ward J
