title: Multiple effects of magnesium isoglycyrrhizinate on the disposition of docetaxel in docetaxel-induced liver injury.
abstract: 1. Magnesium isoglycyrrhizinate (MgIg) has been extensively used in treating liver injury which is the common adverse reaction of docetaxel (DOC). Due to the narrow therapeutic window, small changes in pharmacokinetic profiles can alter the toxicity and therapeutic efficacy of DOC significantly. The study aimed to explore the effects of MgIg on the disposition of DOC and the potential mechanism in DOC-induced liver injury. 2. Pharmacokinetics and tissues distribution behaviors showed that there was no significant difference between DOC group (DOCG) and MgIg + DOC group (MDOCG). The mRNA and protein levels of cytochrome P450 3A1 (CYP3A1) in liver, intestine, and kidney were significantly upregulated, and the P-glycoprotein (P-gp) was obviously downregulated in MDOCG when compared with DOCG. 3. Immunoglobulin M (IgM), CD8+were upregulated in DOCG; while in MDOCG, IgM, CD8+recovered to normal levels and complement C3; CD4+were upregulated. 4. MgIg had no significant effects on the disposition of DOC in docetaxel-induced liver injury. Additional, potential drug-drug interaction may happen if MgIg co-administered with antitumor drugs which are the substrates of CYP3A4 or P-gp. Hepatoprotective mechanism of MgIg perhaps was through upregulation of C3, CD4+and downregulation of IgM, CD8+.
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , P.R. China.
authors.forename: Biao
authors.initials: B
authors.lastname: Qu
authors.affiliation: b Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University , Nanjing , P.R. China , and.|c Department of Pharmacy , The First Affiliated Hospital of Bengbu Medical College , Bengbu , P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xing
authors.affiliation: b Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University , Nanjing , P.R. China , and.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ge
authors.affiliation: a Anhui University of Chinese Medicine , Hefei , P.R. China.
authors.forename: Daiyin
authors.initials: D
authors.lastname: Peng
authors.affiliation: b Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University , Nanjing , P.R. China , and.
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000077143:Docetaxel; D004347:Drug Interactions; D006801:Humans; D012503:Saponins / Q000737:chemistry / Q000633:toxicity*; D043823:Taxoids / Q000737:chemistry / Q000633:toxicity*; D014315:Triterpenes / Q000737:chemistry / Q000633:toxicity*
chemical_list: C521270:18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012503:Saponins; D043823:Taxoids; D014315:Triterpenes; D000077143:Docetaxel; D003577:Cytochrome P-450 Enzyme System
keywords: CYP3A1; P-gp; disposition; docetaxel; liver injury; magnesium isoglycyrrhizinate