Abstract: AIM: To establish an acetaminohpheninduced hepatotoxicity model using precision-cut liver slice (PCLS) technique and observe the regulation of cytochrome P4502E1 (CYP2E1) so as to provide experimental basis on investigating and screening new potential hepatoprotective drugs. METHODS: (1) The PCLS was prepared by the vibratome and co-incubated with 500 μmol/L acetaminophen for 0, 2, 4 and 6 h. The activities of glutathione S-transferase (GST) and lactic acid dehydrogenase (LDH) were measured in the medium and slices. (2) The rats were intragastrically administrated with ethanol in different dosages (0.25, 0.5, 1.0 g/kg) once a day for three days consecutively, then they were at sacrificed 8 h after the last administration and the slices were prepared. And the slices were co-incubated with 500 μmol/L acetaminophen for 6 h and then the activities of ALT and LDH were detected in the slices and medium. (3) Replace the medium after 1 h pre-incubation, the slices were co-incubated with 500 μmol/L acetaminophen and diethyldithiocarbamate(DDTC) (5, 10, 20 μmol/L) for 6 h and the activities of ALT and LDH in the slices and medium were assayed. RESULTS: Compared with regular culture group, the leakage rates of GST and LDH in acetaminophen co-incubated for 4 and 6 h groups were significantly increased (P<0.01). Compared with those in acetaminophen model group, the leakage rates of LDH of ethanol at the dosages of 0.5, 1.0 g/kg and the leakage rates of ALT of ethanol at the dosages of 0.25, 1.0 g/kg increased significantly (P<0.01, P<0.05). Moreover, the leakage rates of ALT in all concentrations of DDTC decreased remarkably (P<0.05). CONCLUSION: Co-incubation PCLS with 500 μmol/L acetaminophen for more than 4 h is a successful way to establish hepatotoxicity in vitro model. The reduction of CYP2E1 activity might protect the slices from acetaminophen-induced hepatotoxicity, while the increase of CYP2E1 activity might aggravate it.

Key words: CYP2E1, ethanol, acetaminophen, precision-cut liver slice technique, liver injury