Effects of chitosan oligosaccharides on drug-metabolizing enzymes in rat liver and kidneys

• Published in: Food and chemical toxicology 2012-05, Vol.50 (5), p.1171-1177
• Main Authors: Yao, Hsien-Tsung, Luo, Mei-Ning, Hung, Lang-Bang, Chiang, Meng-Tsan, Lin, Jia-Hsuan, Lii, Chong-Kuei, Huang, Chun-Yin
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Body Weight - drug effects; chitosan; Chitosan - pharmacology; Chitosan oligosaccharides; Chromatography, High Pressure Liquid; cytochrome P-450; Cytochrome P-450 Enzyme System - metabolism; diet; dodecanoic acid; Drug-metabolizing enzymes; enzyme activity; Glucuronosyltransferase - metabolism; glutathione; Glutathione - metabolism; glutathione transferase; Glutathione Transferase - metabolism; Kidney - drug effects; Kidney - enzymology; Kidneys; Lipid Peroxidation - drug effects; Liver; Liver - drug effects; Liver - enzymology; Male; Medical sciences; metabolic detoxification; oligosaccharides; Oligosaccharides - pharmacology; Organ Size - drug effects; Oxidative stress; Rats; Rats, Sprague-Dawley; testosterone; Toxicology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2012.02.022

► Chitosan oligosaccharides (COS) inhibited CYP enzymes in rat liver. ► COS induced phase II detoxifying reactions in rat liver and kidneys. ► The modulation of COS on the activity of CYP isozymes is tissue-specific. 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 5weeks. 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.