Ratio of microRNA-122/155 in isoniazid-induced acute liver injury in mice

Abstract

Liver injury is a major hindrance to the treatment of tuberculosis (TB) patients due to the primary side effects associated with anti-TB drugs. Several investigations have identified sensitive biomarkers for the early diagnosis of anti-TB drug-induced liver injury (ADLI), including the use of microRNAs (miRNAs/miRs). However, the association between miR-122/155 and ADLI remains unknown. Thus, the present study used reverse transcription-quantitative polymerase chain reaction to observe changes in tissue miR-122/155 expression levels during the course of liver injury in mice. Liver injury was induced by the administration of isoniazid (INH), a first-line anti-TB drug. miR-122/155 expression levels were quantified at seven time points throughout 1 day (0.25, 0.75, 1.5, 6, 12, 18 and 24 h) based on the pharmacokinetics of INH in mice. Notably, over the timecourse of INH-induced liver injury, the tissue miR-122 expression level significantly decreased at 0.25 h, which is the peak concentration time of INH, compared with the control group (P<0.05). The change was more rapid than that of the serum aminotransferase and miR-155, which were significantly increased at 0.75 h. In addition, the pathological score correlated with the ratio of miR-122/miR-155 (r=−0.779; P<0.01). In conclusion, the miR-122/155 ratio may be utilized as a sensitive biomarker for ADLI, which could contribute to the early diagnosis of patients following anti-TB treatment.