Hot off the presses, a new article in Scientific Reports builds on the body of research we reviewed in our recent post about acetaminophen toxicity and microRNA. Dr. James Dear’s lab at Edinburgh University, in collaboration with authors from QIAGEN and from multiple institutions in the UK, examined liver and kidney injury following acetaminophen overdose. By profiling the circulating miRNome, they found effective potential biomarkers for injury to both these organs.
Why are circulating biomarkers for organ injury so important in acetaminophen overdose patients? Livery injury markers are critical for understanding which patients would benefit from receiving treatment. Acetylcysteine is an antidote that can effectively prevent liver damage, but it has unpleasant side effects and requires at minimum 21 hours of treatment. If doctors could identify patients with a lower risk for liver injury, those patients could possibly avoid unnecessary treatment with this drug. Additionally, acute kidney injury can predict whether an individual needs an imminent liver transplant, so it’s important to have reliable markers for this condition. Serum creatinine is currently used as a marker, but can be slow to reflect injury and can also result from unrelated conditions like dehydration.
In this study, the collaborators tested patient samples in 3 phases. First, they used a miRNome qPCR array to find which microRNAs were expressed. Then, they used a custom array with assays for these microRNAs to determine which were differently expressed between APAP-TOX (acetaminophen overdose with organ injury) and APAP-no TOX samples (acetaminophen overdose without organ injury). They found 75 microRNAs upregulated in APAP-TOX samples by 3-fold or more, and 46 that were downregulated by the same magnitude in the APAP-no TOX group. Interestingly, certain microRNAs were lower in patients that had more severe illness, such as miR-30b-5p and miR-186-5p. Others, like miR-122-5p and miR-885-5p, were bound to Ago2 at higher levels in patients with liver injury.
Ultimately, the team identified specific circulating microRNAs indicating liver injury, including miR-122-5p, miR-151a-3p, miR-885-5p and miR-382-5p. Additionally, they pinpointed circulating kidney injury markers, including miR-19a-3p, miR-19b-3p and miR-192-5p. Panels like these may someday help identify patients with and without organ injury following drug overdose, which can lead to better treatment selection.
Want to read more about drug-induced liver injury? Check out our Reviews Online article on how gap junction communication propagates APAP-induced hepatotoxicity!
- Vliegenthart, A.D.B. et al. (2015) Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver and kidney injury. Sci. Rep. 5, 15501.