Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression.
OBJECTIVE
To investigate the hepatoprotective activity of tea polyphenols (TP) and its relation with cytochrome P450 (CYP450) expression in mice.


METHODS
Hepatic CYP450 and CYPb(5) levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP (25, 50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100, 200 and 400 mg/kg per day) for six days before paracetamol (1000 mg/kg) was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP (100, 200, and 400 mg/kg per day) for five days before paracetamol (500 mg/kg) was given. Hepatic CYP2E1 and CYP1A2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction.


RESULTS
The hepatic CYP450 and CYPb(5) levels in mice of TP-treated groups (100, 200 and 400 mg/kg per day) were decreased in a dose-dependent manner compared with those in the negative control mice. TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner.


CONCLUSIONS
TP possess potential hepatoprotective properties and can suppress CYP450 expression.
Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Lvshunkou District, Dalian, Liaoning Province, China.
Xia
X
Chen
Chang-Kai
CK
Sun
Guo-Zhu
GZ
Han
Jin-Yong
JY
Peng
Ying
Y
Li
Yan-Xia
YX
Liu
Yuan-Yuan
YY
Lv
Ke-Xin
KX
Liu
Qin
Q
Zhou
Hui-Jun
HJ
Sun
D000082:Acetaminophen / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000627:therapeutic use*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010636:Phenols / Q000627:therapeutic use*; D059808:Polyphenols; D013662:Tea / Q000737:chemistry*
D018712:Analgesics, Non-Narcotic; D005419:Flavonoids; D007527:Isoenzymes; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D000082:Acetaminophen; D019392:Cytochrome P-450 CYP2E1; D019388:Cytochrome P-450 CYP1A2