TY - JOUR
T1 - Phyllanthus urinaria extract attenuates acetaminophen induced hepatotoxicity
T2 - Involvement of cytochrome P450 CYP2E1
AU - Hau, Desmond Kwok Po
AU - Gambari, Roberto
AU - Wong, Raymond Siu Ming
AU - Yuen, Marcus Chun Wah
AU - Cheng, Gregory Yin Ming
AU - Tong, Cindy Sze Wai
AU - Zhu, Guo Yuan
AU - Leung, Alexander Kai Man
AU - Lai, Paul Bo San
AU - Lau, Fung Yi
AU - Chan, Andrew Kit Wah
AU - WONG, Wai Yeung
AU - Kok, Stanton Hon Lung
AU - Cheng, Chor Hing
AU - Kan, Chi Wai
AU - Chan, Albert Sun Chi
AU - CHUI, Chung Hin
AU - Tang, Johnny Cheuk On
AU - FONG, David W F
N1 - Funding Information:
We acknowledge a Niche area grant offered by the Hong Kong Polytechnic University to Dr. C.H. Chui (HK$200,000; BB8Q) and a postgraduate research fund to Mr. D.K.P. Hau from The Baptist University of Hong Kong (40-40-173 RDD Development Fund). Professor R. Gambari is sponsored by AIRC (Italian Association for Cancer Research). Lastly, Mr. D.K.P. Hau would like to thank the supervision from Professor W.F. Fong and Bioactive Technologies Limited (Hong Kong) for the supply of P. urinaria extract.
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
KW - Acetaminophen
KW - Cytochrome 450 CYP2E1
KW - Hepatoprotection
KW - Hepatotoxicity
KW - Phyllanthus urinaria
UR - http://www.scopus.com/inward/record.url?scp=67349162779&partnerID=8YFLogxK
U2 - 10.1016/j.phymed.2009.01.008
DO - 10.1016/j.phymed.2009.01.008
M3 - Journal article
C2 - 19386480
AN - SCOPUS:67349162779
SN - 0944-7113
VL - 16
SP - 751
EP - 760
JO - Phytomedicine
JF - Phytomedicine
IS - 8
ER -