Small RNAs in anti-tuberculosis drug-induced liver injury

The antimicrobials isoniazid and pyrazinamide, used for the treatment of tuberculosis are known to cause drug-induced liver injury in humans. This limits the effectiveness of tuberculosis treatment, resulting in incomplete cure, relapse and the development of antimicrobial resistance. MicroRNAs are known to be good biomarkers of disease, with the microRNA miR-122 being diagnostic for liver injury. In this study zebrafish larvae were exposed to the anti-tuberculosis drugs isoniazid and pyrazinamide at concentrations which demonstrated liver injury by microscopy and histology. The aim of this study is to understand small RNA changes occurring in anti-tuberculosis drug-induced liver injury and to attempt to identify novel microRNA biomarkers of liver injury. Overall design: Zebrafish larvae were exposed to 6 mM pyrazinamide or 10 mM isoniazid for 24 hours from 4 to 5 days post fertilisation. Control zebrafish larvae were maintained in system water. After drug exposure, larvae were anaesthetised and RNA collected for small RNA sequencing. A total of 24 samples were analysed, 8 in each treatment group. A total of 30 zebrafish larvae were pooled for each sample.