Phyllanthus urinaria extract attenuates acetaminophen induced hepatotoxicity: Involvement of cytochrome P450 CYP2E1

Desmond Kwok Po Hau, Roberto Gambari, Raymond Siu Ming Wong, Marcus Chun Wah Yuen, Gregory Yin Ming Cheng, Cindy Sze Wai Tong, Guo Yuan Zhu, Alexander Kai Man Leung, Paul Bo San Lai, Fung Yi Lau, Andrew Kit Wah Chan, Wai Yeung Wong, Stanton Hon Lung Kok, Chor Hing Cheng, Chi Wai Kan, Albert Sun Chi Chan, Chung Hin Chui, Cheuk On Tang, David Wang Fun Fong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

46 Citations (Scopus)

Abstract

Acetaminophen is a commonly used drug for the treatment of patients with common cold and influenza. However, an overdose of acetaminophen may be fatal. In this study we investigated whether mice, administered intraperitoneally with a lethal dose of acetaminophen, when followed by oral administration of Phyllanthus urinaria extract, may be prevented from death. Histopathological analysis of mouse liver sections showed that Phyllanthus urinaria extract may protect the hepatocytes from acetaminophen-induced necrosis. Therapeutic dose of Phyllanthus urinaria extract did not show any toxicological phenomenon on mice. Immunohistochemical staining with the cytochrome P450 CYP2E1 antibody revealed that Phyllanthus urinaria extract reduced the cytochrome P450 CYP2E1 protein level in mice pre-treated with a lethal dose of acetaminophen. Phyllanthus urinaria extract also inhibited the cytochrome P450 CYP2E1 enzymatic activity in vitro. Heavy metals, including arsenic, cadmium, mercury and lead, as well as herbicide residues were not found above their detection limits. High performance liquid chromatography identified corilagin and gallic acid as the major components of the Phyllanthus urinaria extract. We conclude that Phyllanthus urinaria extract is effective in attenuating the acetaminophen induced hepatotoxicity, and inhibition of cytochrome P450 CYP2E1 enzyme may be an important factor for its therapeutic mechanism.
Original languageEnglish
Pages (from-to)751-760
Number of pages10
JournalPhytomedicine
Volume16
Issue number8
DOIs
Publication statusPublished - 1 Aug 2009

Keywords

  • Acetaminophen
  • Cytochrome 450 CYP2E1
  • Hepatoprotection
  • Hepatotoxicity
  • Phyllanthus urinaria

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine

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