title: Effects of chitosan oligosaccharides on drug-metabolizing enzymes in rat liver and kidneys.
abstract: To investigate the effect of chitosan oligosaccharides (COS) on drug-metabolizing enzymes in rat liver and kidneys, male Spraque-Dawley rats were fed a diet containing 1% or 3% COS for 5 weeks. The activities of cytochrome P450 (CYP) enzymes, UDP-glucurosyltransferase (UGT) and glutathione S-transferase (GST) in the liver and kidneys were determined. Significant decreases in microsomal CYP3A-catalyzed testosterone 6β-hydroxylation, CYP2C-catalyzed diclofenac 4-hydroxylation, and CYP4A-catalyzed lauric acid 12-hydroxylation in the liver of rats fed the COS diets were observed compared with those rats fed the control diet. Immunoblot analyses of CYP proteins showed the same trend as with enzyme activities. Increased glutathione content in liver was found in rats fed the 1% COS diet. Increased hepatic NADPH: quinone oxidoreductase 1 (NQO1) activity was found in rats fed the COS diets. In kidneys, COS had little or no effect on CYP enzyme activities. However, increased GST activity was observed in rats fed the COS diets. Moreover, a higher UGT activity was found in rats fed the 1% COS diet. Our results indicate that COS may suppress hepatic CYP enzymes and induce phase II detoxifying reactions in the liver and kidneys of rats.
authors.affiliation: Department of Nutrition, China Medical University, 91 Hsueh-Shih Road, Taichung 404, Taiwan, ROC. htyao@mail.cmu.edu.tw
authors.forename: Hsien-Tsung
authors.initials: HT
authors.lastname: Yao
authors.forename: Mei-Ning
authors.initials: MN
authors.lastname: Luo
authors.forename: Lang-Bang
authors.initials: LB
authors.lastname: Hung
authors.forename: Meng-Tsan
authors.initials: MT
authors.lastname: Chiang
authors.forename: Jia-Hsuan
authors.initials: JH
authors.lastname: Lin
authors.forename: Chong-Kuei
authors.initials: CK
authors.lastname: Lii
authors.forename: Chun-Yin
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009844:Oligosaccharides / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009844:Oligosaccharides; D048271:Chitosan; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D005978:Glutathione