title: Phyllanthus urinaria extract attenuates acetaminophen induced hepatotoxicity: involvement of cytochrome P450 CYP2E1.
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.
authors.affiliation: Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Desmond Kwok Po
authors.initials: DK
authors.lastname: Hau
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Raymond Siu Ming
authors.initials: RS
authors.lastname: Wong
authors.forename: Marcus Chun Wah
authors.initials: MC
authors.lastname: Yuen
authors.forename: Gregory Yin Ming
authors.initials: GY
authors.lastname: Cheng
authors.forename: Cindy Sze Wai
authors.initials: CS
authors.lastname: Tong
authors.forename: Guo Yuan
authors.initials: GY
authors.lastname: Zhu
authors.forename: Alexander Kai Man
authors.initials: AK
authors.lastname: Leung
authors.forename: Paul Bo San
authors.initials: PB
authors.lastname: Lai
authors.forename: Fung Yi
authors.initials: FY
authors.lastname: Lau
authors.forename: Andrew Kit Wah
authors.initials: AK
authors.lastname: Chan
authors.forename: Wai Yeung
authors.initials: WY
authors.lastname: Wong
authors.forename: Stanton Hon Lung
authors.initials: SH
authors.lastname: Kok
authors.forename: Chor Hing
authors.initials: CH
authors.lastname: Cheng
authors.forename: Chi Wai
authors.initials: CW
authors.lastname: Kan
authors.forename: Albert Sun Chi
authors.initials: AS
authors.lastname: Chan
authors.forename: Chung Hin
authors.initials: CH
authors.lastname: Chui
authors.forename: Johnny Cheuk On
authors.initials: JC
authors.lastname: Tang
authors.forename: David Wang Fun
authors.initials: DW
authors.lastname: Fong
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D005707:Gallic Acid / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D022781:Hepatocytes / Q000187:drug effects; D047348:Hydrolyzable Tannins; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D019216:Metals, Heavy / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000188:drug therapy; D029803:Phyllanthus / Q000737:chemistry; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry
chemical_list: D065691:Cytochrome P-450 CYP2E1 Inhibitors; D005960:Glucosides; D047348:Hydrolyzable Tannins; D019216:Metals, Heavy; D010936:Plant Extracts; D000082:Acetaminophen; C049096:corilagin; D005707:Gallic Acid