Antioxidant properties of high molecular weight dietary chitosan in vitro and in vivo
Introduction
Chitosan, a cationic polysaccharide produced by the N-deacetylation of chitin under alkaline conditions, contains a linear sugar backbone of chitosan composed of β-1,4-linked glucosamine units. It exhibits a wide variety of biological activities, including antitumor activities (Suzuki et al., 1986), immunostimulating effects (Jeon & Kim, 2001), cholesterol-lowering effects (Schipper et al., 1999), antimicrobial effects (Park, Je, Byun, Moon, & Kim, 2004), wound healing effects (Porporatto, Bianco, Riera, & Correa, 2003), antifungal activities, and free radical scavenging activities (Anraku et al., 2008, Park et al., 2004).
Property of particular interest for this study is the antioxidant properties of chitosan (Chiang et al., 2000, Xue et al., 1998). Xie, Xu, and Liu (2001) reported that the scavenging of hydroxyl radicals by chitosan inhibits the lipid peroxidation of phosphatidylcholine and linoleate liposomes. Santhosh, Sini, Anandan, and Mathew (2006) reported that the administration of chitosan to rats that had been treated with isoniazid or rifampicin prevented the oxidation of hepatotoxic lipids. Similarly, chitosan, when injected, inhibited glycerol-induced renal oxidative damage in rats (Yoon et al., 2008). Owing to its many antioxidant studies in vitro and in vivo, chitosan has attracted considerable attention from researchers; however, relationships between molecular weight (MW) and antioxidant activity have not been extensively investigated.
We recently showed that the antioxidant properties of low MW chitosans are substantial, whereas high MW chitosans were much less effective in terms of antioxidant properties (Tomida et al., 2009). In recent, world-wide studies, several MW chitosans were tested as a dietary supplement (Gades and Stern, 2005, Kaats et al., 2006). High MW chitosans would be expected to inhibit the absorption of certain lipids and bile acids. On the other hand, low MW chitosans would be predicted to absorb such substances, but would also be expected to show increased antioxidant effects. In fact, in a previous study, we showed that the administration of low MW chitosan to human volunteers strongly inhibited the oxidation of human serum albumin (HSA) in vivo (Anraku et al., 2009). Although several studies have been reported concerning the antioxidant activities of low MW chitosan, relationships between high MW, low MW chitosans and their antioxidant activity have not been extensively reported in in vivo studies.
In this study, we examined the effect of high MW chitosan supplement (HMCS) on oxidative stress in human volunteers, in an attempt to better understand the potential role for HMCS as an antioxidant in the systemic circulation. Oxidative stress was evaluated by monitoring oxidized serum albumin levels in the systemic circulation, a sensitive marker for protein oxidation (Anraku et al., 2004, Anraku et al., 2009). We also investigated the role of HMCS as a chelator, to verify the mechanism of the antioxidant activity of HMCS in human volunteers.
Section snippets
Materials
A high molecular weight chitosan supplement (HMCS) (Chitosamin®; average molecular weight 100 kDa, degree of deacetylation 90%) was a generous gift from Nippon Kayaku Food Techno Co., Ltd (Gunma, Japan). 1,1′-Diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) were supplied by Nacalai Tesque (Kyoto, Japan). Other chemicals were also of the highest grade commercially available, and all solutions were prepared using deionized, distilled water.
Volunteers
The
Effects of HMCS on biological parameters
The results of blood parameter measurements show that the administration of HMCS for up to 8 weeks had no effect on blood pressure, body-mass index, or blood glucose levels (Table 1). Compared to the corresponding results before the treatment, there was a significant decrease in the levels of total cholesterol and atherogenic index after 8 weeks. However, the concentration of HDL continued to increase during the treatment period while the trend towards lower levels of LDL was not significant at
Discussion
The cholesterol-lowering effect of chitosan is one of its most extensively studied bioactivity. It is generally accepted that the origin of the cholesterol-lowering effect of chitosan is due to its unique ability to bind lipid and bile acids (Gallaher et al., 2000, Ormrod et al., 1998, Ranaldi et al., 2002). The binding results in an increased elimination of fat in the stool, reduced bile acid recycling, and the induction of hepatic synthesis of new bile acid constituents from cholesterol (
Conclusion
The findings reported herein serve to demonstrate the antioxidative potential of HMCS in the systemic circulation in human volunteers. From these results, we hypothesize that HMCS reduces lipid hydroperoxides and other uremic toxins that induce reactive oxygen species (ROS) production in the intestinal tract, thereby inhibiting the subsequent occurrence of oxidative stress in the systemic circulation in human volunteers. Thus, the antioxidative effect of HMCS is unique and differs from that of
Acknowledgements
We wish to thank the Nippon Kayaku Food Techno Co., Ltd (Gunma, Japan) for the generous gift of HMCS (Chitosamin®).
References (33)
- et al.
Antioxidant effects of a dietary supplement: Reduction of indices of oxidative stress in normal subjects by water-soluble chitosan
Food and Chemical Toxicology
(2009) - et al.
Antioxidant protection of human serum albumin by chitosan
International Journal of Biological Macromolecules
(2008) - et al.
Intravenous iron administration induces oxidation of serum albumin in hemodialysis patients
Kidney International
(2004) - et al.
Deoxycholic acid-conjugated chitosan oligosaccharide nanoparticles for efficient gene carrier
Journal of Controlled Release
(2005) - et al.
Chitosan supplementation and fat absorption in men and women
Journal of the American Dietetic Association
(2005) - et al.
Cholesterol reduction by glucomannan and chitosan is mediated by changes in cholesterol absorption and bile acid and fat excretion in rats
The Journal of Nutrition
(2000) Albumin an important extracellular antioxidant?
Biochemical Pharmacology
(1988)- et al.
Potent antiperoxidation activity of the bisbenzylisoquinoline alkaloid cepharanthine: The amine moiety is responsible for its pH-dependent radical scavenge activity
Biochimica et Biophysica Acta
(1999) - et al.
Quantitative evaluation of the antioxidant properties of garlic and shallot preparations
Nutrition
(2006) - et al.
Role for Buremic toxin in the progressive loss of intact nephrons in chronic renal failure
Kidney International
(1991)
Plasma lipids and apolipoproteins as discriminators for presence and severity of angiographically defined coronary artery disease
Atherosclerosis
Dietary chitosan inhibits hypercholesterolaemia and atherogenesis in the apolipoprotein E-deficient mouse model of atherosclerosis
Atherosclerosis
Chitosan induces different L-arginine metabolic pathways in resting and inflammatory macrophages
Biochemical and Biophysical Research Communications
The effect of chitosan and other polycations on tight junction permeability in the human intestinal Caco-2 cell line(1)
The Journal of Nutritional Biochemistry
Effect of chitosan supplementation on antitubercular drugs-induced hepatotoxicity in rats
Toxicology
Chitosans as absorption enhancers of poorly absorbable drugs: 3. Influence of mucus on absorption enhancement
European Journal of Pharmaceutical Sciences
Cited by (66)
Effect of tea polyphenols on chitosan packaging for food preservation: Physicochemical properties, bioactivity, and nutrition
2024, International Journal of Biological MacromoleculesChitosan-based hydrogel wound dressing: From mechanism to applications, a review
2023, International Journal of Biological MacromoleculesMarine polymers and their antioxidative perspective
2022, Marine Antioxidants: Preparations, Syntheses, and ApplicationsAntimicrobial and antioxidant properties of chitosan and its derivatives and their applications: A review
2020, International Journal of Biological Macromolecules
- 1
These authors contributed equally to this work.