Phyllanthus urinaria extract attenuates acetaminophen induced hepatotoxicity: involvement of cytochrome P450 CYP2E1.
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.
Hau
Desmond Kwok Po
DK
Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
Gambari
Roberto
R
Wong
Raymond Siu Ming
RS
Yuen
Marcus Chun Wah
MC
Cheng
Gregory Yin Ming
GY
Tong
Cindy Sze Wai
CS
Zhu
Guo Yuan
GY
Leung
Alexander Kai Man
AK
Lai
Paul Bo San
PB
Lau
Fung Yi
FY
Chan
Andrew Kit Wah
AK
Wong
Wai Yeung
WY
Kok
Stanton Hon Lung
SH
Cheng
Chor Hing
CH
Kan
Chi Wai
CW
Chan
Albert Sun Chi
AS
Chui
Chung Hin
CH
Tang
Johnny Cheuk On
JC
Fong
David Wang Fun
DW
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
D065691:Cytochrome P-450 CYP2E1 Inhibitors; D005960:Glucosides; D047348:Hydrolyzable Tannins; D019216:Metals, Heavy; D010936:Plant Extracts; D000082:Acetaminophen; C049096:corilagin; D005707:Gallic Acid