Effects of Ganoderma lucidum polysaccharide on CYP2E1, CYP1A2 and CYP3A activities in BCG-immune hepatic injury in rats.
The purpose of the present study was to investigate the effect of Ganoderma lucidum polysaccharide (GLPS), a major active component in Chinese medicinal fungus, on cytochrome P450 metabolic activity in Bacillus Calmette Guérin (BCG)-induced immune hepatic injury in rats. The enzyme kinetics of the probes including chlorzoxazone (CYP2E1), phenacetin (CYP1A2) and nifedipine (CYP3A) were evaluated by HPLC. The results showed that BCG-pretreatment (125 mg/kg) significantly increased serum levels of alanine transaminase (ALT), nitrite and malondialdehyde (MDA), inhibited activities of superoxide dismutase (SOD) and decreased P450 total content in microsomes (p<0.05). Administration of GLPS (50 and 200 mg/kg) reversed above hepatic injury stimulated by BCG in vivo. Moreover, GLPS dose-dependently inhibited activities of CYP2E1, CYP1A2 and CYP3A in hepatic microsomes in vitro, suggesting that inhibition of GLPS on P450 oxidative metabolism might participate in the hepatoprotective mechanism, and also suggested that pharmacokinetics might be changed by drug-herb interaction.
Wang
Xin
X
Department of Pharmacology, Basic Medical School, Beijing (Peking) University, Beijing 100083, P. R. China.
Zhao
Xuan
X
Li
Dan
D
Lou
Ya-Qing
YQ
Lin
Zhi-Bin
ZB
Zhang
Guo-Liang
GL
D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000818:Animals; D001500:BCG Vaccine / Q000633:toxicity*; D002753:Chlorzoxazone / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D003640:Dealkylation; D032902:Ganoderma / Q000737:chemistry*; D006505:Hepatitis / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D006900:Hydroxylation; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010084:Oxidation-Reduction; D010615:Phenacetin / Q000378:metabolism; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism