Elsevier

Carbohydrate Polymers

Volume 83, Issue 2, 10 January 2011, Pages 501-505
Carbohydrate Polymers

Antioxidant properties of high molecular weight dietary chitosan in vitro and in vivo

https://doi.org/10.1016/j.carbpol.2010.08.009Get rights and content

Abstract

The effect of high molecular weight chitosan supplement (HMCS), a natural polymer derived from chitin, on indices of oxidative stress was investigated in normal volunteers. The use of HMCS for 8 weeks resulted in a significant decrease in total cholesterol levels and atherogenic index, and increased levels of high density lipoprotein (HDL) cholesterol. HMCS treatment also resulted in a lowered ratio of oxidized to reduced albumin and an increase in total plasma antioxidant activity. A good correlation between the atherogenic index and oxidized albumin ratio was found. The results suggest that the ratio of oxidized to reduced albumin ratio represents a potentially useful marker of the metabolic syndrome. In in vitro studies, HMCS slightly reduced the levels of two stable radicals in a dose- and time-dependent manner. The strong binding capacity of indoxyl sulfate and low density lipoprotein (LDL) cholesterol was also observed with HMCS. These results suggest that HMCS reduces significant levels of pro-oxidants such as cholesterol and uremic toxins in the gastrointestinal tract, thereby inhibiting the subsequent development of oxidative stress in the systemic circulation in humans.

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)

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These authors contributed equally to this work.

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