Evaluation of miR-122 to Predict High Dose Acetaminophen-Induced Liver Injury in Mice: The Combination Uses of 5-Fluorouracil.

Administration of high doses of acetaminophen (APAP) is known to cause drug-induced liver injury (DILI) in humans. Therefore, the detection or prediction of these side-effects at an early stage using appropriate biomarkers is the need of the hour. Micro RNA (miR)-122 is expected to be a novel biomarker for liver injury. However, more evidence is required in various alternate situations such as its use in combination as APAP is often used along with anticancer drugs. In the present study, we aimed to evaluate the functions of miR-122 as a biomarker for liver injury in comparison with alanine aminotransferase (ALT) in a mice model with the APAP-induced liver injury (AILI). Consequently, there was a dose-dependent increase in miR-122 after administration of APAP intraperitoneally. Similar observations were made for ALT activity. Additionally, the expression of miR-122 increased in a more rapid manner compared to ALT activity. However, there was a variation in the miR-122 expression. Further, we investigated the drug-drug interaction between APAP and 5-fluorouracil using miR-122 and ALT in mice. As a result, the degree of AILI was not changed by the use of 5-fluorouracil in combination with APAP in mice.

Determining Transgene Expression Characteristics Using a Suction Device with Multiple Hole Adjusting a Left Lateral Lobe of the Mouse Liver.

We developed a tissue suction-mediated transfection method (suction method) as a relatively reliable and less invasive technique for in vivo transfection. In this study, we determined hepatic transgene expression characteristics in the mouse liver, using a suction device, collecting information relevant to gene therapy and gene functional analysis by the liver suction method. To achieve high transgene expression levels, we developed a suction device with four holes (multiple hole device) and applied it to the larger portion of the left lateral lobe of the mouse liver. Hepatic transfection with physical stimuli was potentially controlled by activator protein-1 (AP-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). We examined the spatial distribution of transgene expression in the suctioned lobe by 2-dimensional imaging with histochemical staining and 3-dimensional multicolor deep imaging with tissue clearing methods. Through monitoring spatial distribution of transgene expression, the liver suction method was used to efficiently transfect extravascular hepatocytes in the suction-deformable upper lobe of the liver. Moreover, long-term transgene expression, at least 14 d, was achieved with the liver suction method when cytosine-phosphate-guanine (CpG)-free plasmid DNA was applied.