The present study investigated and compared the effects of different molecular weights of chitosan (high molecular weight chitosan (HC) and low molecular weight chitosan (LC)) and its derivatives (chitosan oligosaccharide (CO)) on cholesterol regulation in high-fat (HF) diet-fed rats. A diet supplementation of 5% HC, 5% LC, or 5% CO for 8 weeks showed hypocholesterolemic potential in HF diet-fed rats. Unexpectedly, a 5% CO-supplemented diet exerted hepatic damage, producing increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-alpha (TNF-α). The supplementation of HC and LC, unlike CO, significantly decreased the hepatic total cholesterol (TC) levels and increased the fecal TC levels in HF diet-fed rats. The hepatic protein expression of the peroxisome proliferator-activated receptor-α (PPARα) in the HF diet-fed rats was markedly decreased, which could be significantly reversed by both HC and LC, but not CO, supplementation. Unlike the supplementation of CO, both HC and LC supplementation could effectively reverse the HF-inhibited/induced gene expressions of the low-density lipoprotein receptor (LDLR) and cholesterol 7α-hydroxylase (CYP7A1), respectively. The upregulated intestinal acyl-CoA cholesterol acyltransferase 2 (ACAT2) protein expression in HF diet-fed rats could be reversed by HC and LC, but not CO, supplementation. Taken together, a supplementation of 5% CO in HF diet-fed rats may exert liver damage via a higher hepatic cholesterol accumulation and a higher intestinal cholesterol uptake. Both HC and LC effectively ameliorated the hypercholesterolemia and regulated cholesterol homeostasis via the activation and inhibition of hepatic (AMPKα and PPARα) and intestinal (ACAT2) cholesterol-modulators, respectively, as well as the modulation of downstream signals (LDLR and CYP7A1).

We concluded that apocynin suppressed NADPH oxidase activation and subsequent liver injuries owing to high-cholesterol intake in rats. The impacts of cholesterol metabolism disorders on pathogenesis and progression of steatohepatitis warrant further clinical investigation.

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Chitosan is sold worldwide as a lipid-lowering functional food and may be taken with certain medications. To investigate the effect of chitosan on drug-metabolizing enzymes and oxidative stress in the liver, male Wistar rats were fed a low- or high-fat diet with cellulose or chitosan for 4 weeks. A significant decrease in cytochrome P450 (CYP) 3A-catalyzed testosterone 6beta-hydroxylation in liver microsomes was observed in rats fed the chitosan with low- and high-fat diets. The expression of CYP 3A1 and 3A2, however, was suppressed by chitosan in rats fed the low-fat diet only. Furthermore, rats fed the low-fat diet with chitosan had lower hepatic glutathione S-transferase (GST) activity and superoxide dismutase activity and higher total tissue and microsomal lipid hydroperoxides. Hepatic alpha-tocopherol was lower in rats fed the chitosan-containing diet. The results suggest that chitosan is likely to modulate CYP 3A activity and protein expression and GST activity partially in a dietary fat-dependent manner. This change may cause a decrease in the metabolism of drugs catalyzed by these enzymes in liver tissues. Moreover, decrease of alpha-tocopherol level and SOD activity by chitosan partly accounts for the increase of hepatic lipid peroxidation.

Phytonutrients may play important roles in human health and yet only recently a few studies have described phytonutrient consumption patterns, using data obtained from daily consumption methods. We aimed to estimate the phytonutrient content in Taiwanese diets and analyzed main food sources of 10 major phytonutrients. In this study, food items and dietary data gathered with the 24-hour dietary recall from 2908 participants in the 2005-2008 Nutrition and Health Survey in Taiwan were used to create a food phytonutrient database with 933 plant-based foods through integrating database, literature search, and chemical analysis and to appraise phytonutrient consumption status of participants. SUDAAN (Survey Data Analysis) was used for generating weighted phytonutrient intake estimates and for statistical testing. In Taiwanese adults, ∼20% met the recommended number of servings for fruits and 30% met that for vegetables from the Taiwan Food-Guide recommendations. However, only 7.4% consumed the recommended numbers for both fruits and vegetables. Those meeting the recommendations tended to be older and with more females compared with those who did not. Phytonutrient intake levels were higher in meeters than nonmeeters. More than 60% of α-carotene, lycopene, hesperetin, epigallocatechin 3-gallate, and isoflavones came from a single phytonutrient-specific food source. In addition, sweet potato leaf, spinach, and water spinach were among the top three sources of multiple phytonutrients. Cross-comparison between this study and two previous studies with similar methodology showed higher mean levels of lycopene and quercetin in the United States, anthocyanidins in Korea, and lutein and zeaxanthin in Taiwan. The Taiwanese phytonutrient pattern is different from that of the Korean and American. It would be interesting to relate phytonutrient patterns to health profiles in the future.