Chimeric mice with humanized liver that are repopulated with human hepatocytes are useful to study hepatitis B and C viruses, predict drug metabolism and pharmacokinetics (PK), and evaluate hepatotoxicity. Understanding the characteristics of chimeric mice is important for making predictions in humans. In general, chimeric mice with more than 70% of replacement indexes (RIs), a value representing the occupancy ratio of the region of the human liver to that of the mouse liver, are used. However, chimeric mice with RIs less than 70% are also useful in understanding the species differences between mice and humans. In this study, to elucidate the effects of proliferating human hepatocytes and remaining mouse hepatocytes on bile acid concentrations in detail, we investigated the differences in the total concentrations of bile acids and their compositions in chimeric mice with different RIs. The total concentrations of bile acids in their sera increased as the RIs increased. The ratios of primary to secondary bile acids, percentages of glycine conjugates, and hydrophobicity indexes, obtained upon classifying bile acids based on their compositions in the serum and comparing them with those in normal mice and humans, were found to approach the values observed in humans as the RIs increased. The percentages of taurine conjugates were high in chimeric mice with high RIs, although their values were close to those in humans. These results could be fundamental in providing knowledge to accurately predict human PK and toxicity in chimeric mice with humanized liver.

Cadmium (Cd) is an environmental toxic heavy metal that causes renal dysfunction. Cd triggers renal dysfunction through proximal tubular cell toxicity. Our previous study demonstrated that Cd changed the activities of various transcription factors in human proximal tubular HK-2 cells. Interestingly, several GATA family members were included in the transcription factors whose activities were decreased by Cd treatment. The GATA family has diverse roles in cell proliferation, tissue development, disease regulation, and carcinogenesis. In this study, we examined whether knockdown of GATA family members affected the viability of HK-2 cells. The single knockdown of GATA1, GATA3 or GATA6 using siRNA significantly decreased HK-2 cell viability. In particular, GATA6 knockdown led to the greatest effect on HK-2 cells viability. Cd increased mRNA levels of GATA3 and GATA6 but did not affect that of GATA1. The GATA family may regulate the expression of downstream factors involved in common pathway. Therefore, the effect of combined knockdown of GATA1/3/6 on the viability of HK-2 cells was examined. Our results indicated that the effect on HK-2 cell viability following knockdown of multiple GATA family members was comparable to the single knockdown of GATA6. These results suggest, therefore, that multiple GATA family members may be involved in modulating Cd renal toxicity through a common pathway.

We prepared blended oil using soybean oil (SR10) and rapeseed oil (SR01), and evaluated the quality of deteriorated pure and blended oils (with weight/volume ratio of soybean oil to rapeseed oil of 2:1, 1:1, and 1:2) by heat treatment and aeration. The ratio of the acid value following deterioration (AV) to its initial value (AV₀) i.e., the value of AV/AV₀ was in the order SR10 (3.29) << SR01 (7.50). On the other hand, the ratio of the carbonyl value after deterioration (CV) to its initial value (CV₀) i.e., the value of CV/CV₀ decreased with increase in the proportion of rapeseed oil in the blended oil (SR01 (3.12) << SR10 (4.15)). We thus establish that the fatty acid component of the blended oil is a very important factor in the deterioration of edible oil by heat treatment and aeration. Next, we evaluated the improvement in the quality of deteriorated oil by calcium silicate adsorbent (Ca:Si = 1:3, CAS30) treatment i.e., adsorption. It is established that CAS30 exhibited the ability to remove AV and CV from deteriorated oil (treatment temperature: 80 °C < 100 °C). Moreover, we investigated the removal mechanism of AV and CV, and determined good positively or negatively linear relationship between AV or CV removal by CAS30 and the proportion of unsaturated fatty acid in deteriorated pure and blended oils. In summary, the results obtained from treatment with CAS30 provided useful information on improvement in the quality of deteriorated blended oil.