title: Effects of zedoary turmeric oil on P450 activities in rats with liver cirrhosis induced by thioacetamide.
abstract: The aim of this study was to elucidate the effects of zedoary turmeric oil (ZTO) on P450 activities (CYP1A2, CYP2C9, CYP2C19, CYP2B6, CYP2D6 and CYP3A4) in rats with liver cirrhosis induced by thioacetamide (TAA). For the induction of liver cirrhosis, rats were given TAA in their drinking water at a concentration of 0.03% for consecutive 5 weeks and then 0.04% for the next consecutive 5 weeks throughout the establishment of cirrhosis. Then the cirrhotic rats were ip given saline, ZTO 100, 200 and 400 mg/kg, respectively, once daily for 2 weeks. When cirrhosis model was established at week 10, all rats of five groups were administered intragastrically with 15 mg/kg phenacetin, 0.6 mg/kg tolbutamide, 15 mg/kg omeprazole, 15 mg/kg bupropion, 15 mg/kg metoprolol, and 10 mg/kg midazolam. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The degree of liver cirrhosis was assessed by HE staining. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from the model group increased by approximately 4-fold, and a decreased level of albumin (Alb) was also observed, as compared to the control group (P < 0.05). However, ZTO was found to reverse those changes of serum levels observed in the model group, and the 200 mg/kg ZTO treatment group showed the most obvious reverse tendency with significantly decreased ALT, AST and increased Alb levels (P < 0.05). The results indicated that ZTO with the dose of 100 mg/kg could inhibit the activities of CYP450 isoforms CYP2C9 and CYP2D6 in vivo in cirrhotic rats induced by TAA, while ZTO with the dose of 400 mg/kg could induce the activity of CYP2C19 in vivo in cirrhotic rats induced by TAA. However, ZTO showed no influence on cirrhotic rat hepatic CYP1A2, CYP2B6 and CYP3A4 activity in vivo. This has certain guiding significance to clinical treatment.
authors.affiliation: Affiliated Stomatology Hospital, Wenzhou Medical University Wenzhou, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Cheng
authors.affiliation: The First Affiliated Hospital, Wenzhou Medical University Wenzhou, China.
authors.forename: Nai-Bin
authors.initials: NB
authors.lastname: Yang
authors.affiliation: The First Affiliated Hospital, Wenzhou Medical University Wenzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wu
authors.affiliation: The First Affiliated Hospital, Wenzhou Medical University Wenzhou, China.
authors.forename: Jia-Le
authors.initials: JL
authors.lastname: Lin
authors.affiliation: The First Affiliated Hospital, Wenzhou Medical University Wenzhou, China.
authors.forename: Ge-Xin
authors.initials: GX
authors.lastname: Dai
authors.affiliation: Laboratory Animal Center, Wenzhou Medical University Wenzhou, China.
authors.forename: Jia-Yin
authors.initials: JY
authors.lastname: Zhu
mesh_terms: D000818:Animals; D030024:Curcuma; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004195:Disease Models, Animal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide
chemical_list: D010936:Plant Extracts; D013853:Thioacetamide; D003577:Cytochrome P-450 Enzyme System
keywords: CYP450; Zedoary turmeric oil; liver cirrhosis; rat; thioacetamide