Tea Polyphenols On Cytochrome P450 And B₅ Content And Expression Of CYP2E1 And CYP1A2 In Male Mice

Objective: To investigate the effect of tea ployphenols (TPs) on the level of hepatic cytochrome P450 (CYP450) and b₅ along with the expression of CYP2E1 and CYP1A2 in mice after short time taking TPs.Methods: 1. Kunming male mice were intraperitoneally injected with TPs at the doses of 25, 50 and 100 mg/ kgï¹’d^- for two days. The positive control group was given chloramphenicol at the dose of 50 mg/kgï¹’d^- 1h before killing the mice. The negative control group was given the same volume of saline solution. After the mice were killed by decapitation, The livers were removed and microsomes were isolated and then, the contents of CYP450 and b5 were measured by UV-spectrophotometry and compared with control group mice. 2. To evaluate the detoxification effect of TPs, the male mice were intragastricly pre-treated with TPs at the doses of 100, 200 and 400 mg/ kgï¹’d^- for six days, The positive control group was given N-Broncholysin at the dose of 900 mg/kgï¹’d^-. The negative control group was given the same volume of saline solution and then, all the mice were given paracetamol at the dose of 1000 mg/kg. The acute mortality was compared with control mice. 3. To examine the expression of CYP2E1 and CYP1A2, male mice were pre-treated with TPs (100, 200, and 400 mg/kgï¹’d^-) for five days. The model group and the negative control group were given the same volume of saline solution. Then the mice were given paracetamol at the dose of 500 mg/kg 1 hour later after the last time TPs administration except the mice in negative control group. The livers were removed immediately and washed with cold saline solution .Then all specimens were fixed in formalin for histological examinations or snap-frozen in liquid nitrogen and stored at -80℃for protein and RNA extraction. CYP2E1 and CYP1A2 protein and mRNA expression levels in the liver were evaluated by western blotting, immunohistochemical staining and RT-PCR.Results: The contents of CYP450 and b5 in the livers of mice in three TPs-treated groups were dose-dependently decreased compared with the negative control mice (P<0.01) after short time taking TPs. TPs treatment significantly improved hepatic lesions and led to a dramatic reduction of the mortality of paracetamol-treated mice. TPs treatment resulted in a significant reduction of the CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner (P<0.01).Conclusions:1. TPs could suppress both CYP450 and b5 in a dose dependent manner after short time administration.2. In the paracetamol induced mouse liver injury model, TPs demonstrated obvious hepato-protective effects dose-dependently which were shown by substantially lowering the mortality of mice and obviously improving hepatic lesions.3. In the paracetamol induced mouse liver injury model, TPs could supressed CYP450 isoform CYP2E1 and CYP1A2 expression to defend paracetamol-induced liver damage. This result suggested TPs could reduced paracetamol's metabolism and decrease the production of the hepatotoxic N-acetyl-p-benzoquinonimine by suppressing genetic transcription of CYP2E1 and CYP1A2. This might be one of the mechanisms to hepato-protective effects of TPs.