Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression

World J Gastroenterol. 2009 Apr 21;15(15):1829-35. doi: 10.3748/wjg.15.1829.

Abstract

Aim: 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.

Conclusion: TP possess potential hepatoprotective properties and can suppress CYP450 expression.

MeSH terms

  • Acetaminophen / toxicity*
  • Analgesics, Non-Narcotic / toxicity*
  • Animals
  • Cytochrome P-450 CYP1A2 / genetics
  • Cytochrome P-450 CYP1A2 / metabolism*
  • Cytochrome P-450 CYP2E1 / genetics
  • Cytochrome P-450 CYP2E1 / metabolism*
  • Dose-Response Relationship, Drug
  • Flavonoids / therapeutic use*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Phenols / therapeutic use*
  • Polyphenols
  • Tea / chemistry*

Substances

  • Analgesics, Non-Narcotic
  • Flavonoids
  • Isoenzymes
  • Phenols
  • Polyphenols
  • Tea
  • Acetaminophen
  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 CYP1A2