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The metabolic syndrome is a constellation of risk factors, including atherogenic dyslipidemia, impaired fasting glucose, hypertension, and central adiposity, predisposing to higher risks of oxidative stress, type 2 diabetes and atherosclerotic cardiovascular disease. [1][2][3][4] In particular, an enhancement in oxidative stress by reactive oxygen species (ROS) has been proposed as a common pathomechanism by which cardiovascular risk factors affect the vessel wall to induce and amplify vessel and organ injury. Thus, an appropriate evaluation and reduction in oxidative stress in the circulating blood is important from the viewpoint of protecting vascular endothelium and vascular smooth muscle cells against oxidative stress.5-7) Dietary modifications, which include the use of antilipidemic supplements, are one of the key elements in the management of these metabolic abnormalities. For example, chitosan has been proposed as a safe and efficacious dietary supplement that can contribute to weight loss by reducing the amount of dietary fat absorbed, thereby improving calorie balance. 8)Chitosan, a cationic polysaccharide produced by the Ndeacetylation of chitin under alkaline conditions, contains a linear sugar backbone, composed of b-1,4-linked glucosamine units. It exhibits a wide variety of biological activities except for cholesterol-lowering effects.9-11) A property of particular interest for this study is the antioxidant properties of chitosan. Santhosh et al. reported that the administration of chitosan to rats that had been treated with isoniazid or rifampicin inhibited the oxidation of hepatotoxic lipids.12) It had also been reported that chitosan, when injected, inhibited glycerol-induced renal oxidative damage in rats.13) Because of the numerous in vitro and in vivo antioxidant studies that have appeared, chitosan has attracted considerable attention from researchers. In spite of this, however, relationships between molecular weight (MW) and antioxidant activity have not been extensively investigated in in vivo studies.In this study, we examined the effect of high and low MW chitosan supplements (HMC; 1000 kDa and LMC; 30 kDa) on oxidative stress in normal and metabolic syndrome model rats, in an attempt to better understand the potential role for HMC and LMC as an antioxidant in the systemic circulation. Oxidative stress was evaluated by monitoring oxidized serum albumin levels, a sensitive marker for protein oxidation, in the systemic circulation.14,15) We also investigated the role of HMC and LMC as a chelator, to develop a better understanding of the mechanism of the antioxidant activity of HMC and LMC in metabolic syndrome model rats. MATERIALS AND METHODSMaterials LMC (MWϭ30 kDa) and HMC (MWϭ1000 kDa) were obtained from Nippon Kayaku Food Techno Co., Ltd. (Gunma, Japan). All other chemicals were of the highest grade available and were obtained from commercial sources.Animals and Treatment Male (6 weeks old) Wistar Kyoto rats as a normal model (Normal-rats) and spontaneously hypertensive rat/ND mcr-cp ...

The antioxidant properties of different low molecular weight (LMW) chitosans (CS1; 22 kDa, CS2; 38 kDa, CS3; 52 kDa, CS4; 81 kDa) were examined for possible use in extended-release tablets. The criteria used were the ability of the chitosans to reduce Cu2+, and hydroxyl and superoxide radicals and N-centered radicals derived from 1,1'-diphenyl-2-picrylhydrazyl, via the use of ESR spectrometry. CS2 showed the highest scavenging activity. CS1 and CS3, however, were much less effective and CS4 was not a viable antioxidant. The results suggest that CS2 could be useful in combating the development of oxidative stress. A series of chitosan tablets were prepared using a spray drying method and evaluated as an extended-release matrix tablet using theophylline (TPH) as a model drug. The release of TPH from the different MW chitosan tablets increased with increasing MW of the chitosan used. CS2, CS3 and CS4 showed a reasonable release activity, but CS1 showed the shortest release activity. Moreover, the CS2-TPH tablet showed the highest scavenging activity of the three chitosan tablets (CS2-CS4) using 2,2’-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radicals. These results suggest that a CS2-TPH tablet could be potentially useful in an extended-release matrix tablet with a high antioxidant activity.