Changes in mRNA Expression and Activity of Xenobiotic Metabolizing Enzymes in Livers from Adjuvant-Induced Arthritis Rats
Changes in mRNA Expression and Activity of Xenobiotic Metabolizing Enzymes in Livers from Adjuvant-Induced Arthritis Rats作者机构：Department of Pharmacy School of Pharmacy Kinki University Osaka Japan Department of Pharmacy School of Pharmacy Kinki University Osaka Japan.
出 版 物：《Pharmacology & Pharmacy》 (药理与制药（英文）)
年 卷 期：2013年第4卷第6期
页 面：478-483页
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：Inflammation Arthritis Enzyme Cytochrome Metabolism
摘 要：Pathophysiological changes in human patients and in animal models of infection or inflammation are associated with alterations in the production of numerous liver-derived proteins including metabolizing enzymes. In this study, the effects of adjuvant-induced arthritis (AA) in rats on the levels of mRNA and activity of hepatic xenobiotic metabolizing enzymes were determined during the inflammatory response. The mRNA levels of cytochrome P450 (CYP) 1A2, CYP2C12, CYP2D1, CYP2D2, and CYP3A1 were significantly decreased compared with control levels in almost all phases of inflammation. A reduction in the activity of CYP2C and CYP3A, which are abundantly expressed in the liver, was also observed. For phase II metabolizing enzymes, mRNA levels of uridine 5’-diphospho-glucuronosyltransferase (UGT) 1A1, UGT1A6, sulfotransferase (SULT) 2A1, and glutathione S-transferase 2 were significantly decreased compared with control levels. However, the mRNA levels of UGT2B and SULT1A1 returned to control levels during the subacute (7 d after adjuvant treatment) and chronic (21 d after adjuvant treatment) phases although these levels decreased during the acute (3 d after adjuvant treatment) phase. These results suggest that the effects of inflammation on the expression of xenobiotic metabolizing enzymes differ depending on the isoform of the enzyme and could affect the pharmacokinetics of each substrate.
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