Conclusions
Kuhuang could alleviate CPZ-induced cholestatic liver injury by activating PPARγ to reduce oxidative stress. Applying kuhuang for the treatment of CPZ-induced liver injury could be suggested.
Methods
The TE livers (n = 25) were divided into 5 groups (n = 5 livers/group) as 3D, 3D + CPZ, 3D + CPZ + KH, 3D + CPZ + GW9662 (a PPARγ inhibitor) and 3D + CPZ + KH + GW9662. The treatments with kuhuang (1 mg/mL) and GW9662 (10 μmol/L) were given to the desired groups on the 7th day of the experimental process. 20 μmol/L CPZ was added on the 8th day.
Objective
This study uses a new 3D tissue-engineered (TE) liver platform to study the ability of kuhuang to ameliorate liver injury induced by chlorpromazine (CPZ) and the possible mechanisms involved. Materials and
Results
According to the 2D experimental results, the minimum effective concentration of kuhuang is 10 μg/mL and the optimal effective concentration is 1 mg/mL. Kuhuang ameliorated tissue damage in the TE livers both in terms of tissue structure and culture supernatant. Kuhuang significantly reduced TBA accumulation (38%) and downregulated CYP7A1 (38%) and CYP8B1 (79%). It reduced hepatic levels of ROS (14%), MDA (27%) but increased the levels of GSH (41%), SOD (12%), BSEP (4.4-fold), and MRP2 (74%). Moreover, kuhuang downregulated DR5 (99%) but increased the mRNA expression of PPARγ (4-fold). Molecular docking analyses determined the bioactivity of the active compounds of kuhuang through their specific bindings to PPARγ. Conclusions: Kuhuang could alleviate CPZ-induced cholestatic liver injury by activating PPARγ to reduce oxidative stress. Applying kuhuang for the treatment of CPZ-induced liver injury could be suggested.