MicroRNA-122 (miR-122) is an interesting and well-known candidate biomarker of direct liver injury but less data about correlation in indirect liver injury. Here, we used CD-1 mice to induced indirect acute liver injury after 1) acute kidney dysfunction induced by bilateral ureter obstruction (BUO) and bilateral nephrectomy (BiNX) 2) cecal ligation and puncture (CLP), in comparison with a direct liver injury model induced by ischemic and reperfusion of liver (liver I/R). Liver was collected and staining for study histology and serum biomarkers; alanine transaminase (ALT), serum creatinine (sCr), pro and anti-inflammatory cytokines were measured at different time points. Serum cytokines, ALT increased approximately 1.5x of baseline at 6 h in indirect liver injury models without miR-122 expression. Then, miR-122 was detected at 24h with high cytokines, ALT and hepatocyte vacuolization in histopathology. By the different time-points of miR-122 and cytokines detection, we hypothesized that cytokines induced miR-122 and test in vitro. HepG2 cells were incubated with cytokines for 24h showed the up-regulation of miR-122. In contrast, in direct liver injury (liver I/R), ALT was increased 5 folds and 22 folds at 0.5h and 1h, respectively. The sensitivity and specificity of miR-122 in comparison with ALT>40U/L as a standard of liver injury were 68% and 70%, respectively. In conclusion, miR-122 might had a limitation in detecting liver injury with ALT less than 100 U/L.

Thesis (M.Sc.)--Chulalongkorn University, 2014