Protective effect of dietary chitosan on cadmium accumulation in rats.

BACKGROUND/OBJECTIVES: Cadmium is a toxic metal that is an occupational and environmental concern especially because of its human carcinogenicity; it induces serious adverse effects in various organs and tissues. Even low levels of exposure to cadmium could be harmful owing to its extremely long half-life in the body. Cadmium intoxication may be prevented by the consumption of dietary components that potentially reduce its accumulation in the body. Dietary chitosan is a polysaccharide derived from animal sources; it has been known for its ability to bind to divalent cations including cadmium, in addition to other beneficial effects including hypocholesterolemic and anticancer effects. Therefore, we aimed to investigate the role of dietary chitosan in reducing cadmium accumulation using an in vivo system. MATERIALS/METHODS: Cadmium was administered orally at 2 mg (three times per week) to three groups of Sprague-Dawley rats: control, low-dose, and high-dose (0, 3, and 5%, respectively) chitosan diet groups for eight weeks. Cadmium accumulation, as well as tissue functional and histological changes, was determined. RESULTS: Compared to the control group, rats fed the chitosan diet showed significantly lower levels of cadmium in blood and tissues including the kidneys, liver, and femur. Biochemical analysis of liver function including the determination of aspartate aminotransferase and total bilirubin levels showed that dietary chitosan reduced hepatic tissue damage caused by cadmium intoxication and prevented the associated bone disorder. CONCLUSIONS: These results suggest that dietary chitosan has the potential to reduce cadmium accumulation in the body as well as protect liver function and bone health against cadmium intoxication.

The inhibitory effect of genistein on hepatic steatosis is linked to visceral adipocyte metabolism in mice with diet-induced non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) has been deeply associated with visceral adiposity, adipose tissue inflammation and a variety of adipocytokines. We reported previously that genistein inhibited NAFLD by enhancing fatty acid catabolism. However, this molecular approach focused on hepatic metabolism. Thus, we have attempted to determine whether this anti-steatotic effect of genistein is linked to visceral adipocyte metabolism. C57BL/6J mice were fed on normal-fat (NF) diet, high-fat (HF) diet and HF diet supplemented with genistein (1, 2 and 4 g/kg diet) for 12 weeks. Mice fed on the HF diet gained body weight, exhibited increased visceral fat mass and elevated levels of serum and liver lipids, and developed NAFLD, unlike what was observed in mice fed on the NF diet. However, genistein supplementation (2 and 4 g/kg diet) normalised these alternations. In the linear regression analysis, visceral fat (R 0·77) and TNFα (R 0·62) were strongly correlated with NAFLD among other NAFLD-related parameters. Genistein supplementation suppressed the hypertrophy of adipocytes via the up-regulation of genes involved in fatty acid ß-oxidation, including PPARα, 5'-AMP-activated protein kinase and very long-chain acyl CoA dehydrogenase, as well as through the down-regulation of genes associated with adipogenesis or lipogenesis, including liver X receptor-α, sterol-regulatory element-binding protein-1c, PPARγ, retinoid X receptor-α and acetyl CoA carboxylase 2. Moreover, genistein supplementation augmented an anti-steatohepatitic adiponectin TNF and reduced a steatohepatitic TNFα. Collectively, these findings show that genistein may prevent NAFLD via the regulation of visceral adipocyte metabolism and adipocytokines.

Dietary fish oil alleviates soleus atrophy during immobilization in association with Akt signaling to p70s6k and E3 ubiquitin ligases in rats.

Reduced muscle activity leads to impaired insulin signaling, which leads to loss of contractile proteins and muscle mass via the Akt pathway. Dietary fish oil rich in long chain n-3 polyunsaturated fatty acids has been shown to prevent insulin signaling resistance in skeletal muscle. This study was conducted to elucidate the protective effect of dietary fish oil on disuse-induced perturbations in insulin signaling and soleus muscle atrophy. To accomplish this, rats were fed a corn-oil- (control) or fish-oil-based diet for 2 weeks, and then subjected to hindlimb immobilization while still receiving the same diets. After 10 days of immobilization, the soleus muscle mass and myosin heavy chain level had markedly decreased; however, these losses were significantly suppressed in rats fed dietary fish oil, compared with the control group. Dietary fish oil nearly completely attenuated the disturbances in activation of the Akt and p70 S6 kinase proteins, as well as the gene expression of muscle-specific E3 ubiquitin ligases (muscle atrophy F-box and muscle RING finger 1). However, insulin receptor substrate 1 associated with the p85 subunit of phosphoinositide 3-kinase was not altered during immobilization. Dietary fish oil also inhibited alterations in the gene expression of cyclooxygenase-2 and inducible nitric oxide synthase, with no additional observation of oxidative stress. Collectively, these findings indicate that dietary fish oil prior to and during immobilization may alleviate the immobilization-induced soleus muscle atrophy, at least in part, via the Akt pathway through E3 ubiquitin ligases and p70s6k.

Effects of sn-2 palmitic acid-fortified vegetable oil and fructooligosaccharide on calcium metabolism in growing rats fed casein based diet.

This study was carried out to investigate the efficacy of sn-2 palmitic acid-fortified vegetable oil (Sn2PA) on calcium absorption and to confirm the synergistic effects of fructooligosaccharide on calcium absorption. Male SD rats were fed 6 kinds of casein based diets containing vegetable oil (control), sn-2 palmitic acid-fortified vegetable oil (Sn2PA) and Sn2PA with fructooligosaccharide(Sn2PAFO) in two levels of calcium (normal 0.5% and high 1.0%) for 3 weeks. Total lipids, cholesterol, triglyceride and calcium in blood were measured. Feces were collected using cages for 4 days. Serum concentrations of total lipids and calcium were not significantly different among groups. However, serum triglyceride was significantly decreased by fructooligosaccharide supplementation regardless of dietary calcium level. The lipid absorption was not significantly different among experimental groups. Calcium absorption was significantly higher in Sn2PAFO group than other groups. Calcium solubility of intestine was increased by sn-2 palmitic acid supplementation. These results suggest that sn-2 palmitic acid and fructooligosaccharide supplementation could be beneficial for baby foods including infant formula, with regard to increasing absorption of calcium by more soluble calcium in the small intestinal content.

Effects of soy isoflavone and/or estrogen treatments on bone metabolism in ovariectomized rats.

This study investigated whether soy isoflavone intake, with or without estrogen treatment, can reduce postmenopausal bone loss, and whether soy isoflavones can be an alternative for estrogen replacement therapy using a postmenopausal osteoporotic rat model in which ovariectomized female rats were fed a low calcium, high fat diet. Nine-week-old female Sprague-Dawley rats were ovariectomized and then fed low (0.1%) calcium diets with or without soy isoflavone supplementation (80 or 160 ppm) for 6 weeks. Some ovariectomized rats were fed the same diets but also injected with estrogen (10 microg/kg of body weight) subcutaneously. Serum calcium and phosphate levels were normal in all rats. Serum alkaline phosphatase activities were not affected by the treatments. Serum tartrate-resistant acid phosphatase activities and urinary hydroxyproline levels were not different between experimental groups. Bone mineral (calcium and phosphorus) contents were increased in the rats supplemented with 80 ppm soy isoflavone or the rats treated with only estrogen without soy isoflavone. Therefore, the effect of 80 ppm soy isoflavone supplementation was the same as estrogen injection, but there was no beneficial effect from combining soy isoflavones and estrogen injections. When 160 ppm soy isoflavone was used, the benefits were lessened or disappeared altogether. These results suggest that appropriate soy isoflavone supplementation prevents postmenopausal bone loss without estrogen injection and may have efficacy as an alternative to estrogen therapy.

The novel cytokine p43 stimulates dermal fibroblast proliferation and wound repair.

The multifunctional cytokine p43 acts on endothelial and immune cells to control angiogenesis and inflammation. In this report, we describe an additional activity of p43 that specifically promotes fibroblast proliferation and wound repair. In skin wound regions from mice, tumor necrosis factor-alpha induced p43 expression and secretion from macrophages recruited to the site. p43 also promoted fibroblast proliferation through its 146-amino acid N-terminal domain as revealed by deletion mapping. This p43-induced fibroblast proliferation was mediated by extracellular signal-regulated kinase (Erk). Depletion of endogenous p43 in mice by gene disruption retarded wound repair, whereas exogenous supplementation of recombinant human p43 to the wound area stimulated dermal fibroblast proliferation, collagen production, and wound closure. Thus, we have identified a novel p43 activity involving the stimulation of fibroblast proliferation, which could be applied therapeutically to aid wound repair.

Changes of gene expression profiles during neuronal differentiation of central nervous system precursors treated with ascorbic acid.

Ascorbic acid (AA) has been shown to increase the yield of dopaminergic (DA) neurons derived from basic fibroblast growth factor (bFGF)-expanded mesencephalic precursors. To understand the molecular mechanisms underlying this phenomenon, we used cDNA microarray analysis to examine differential expression of neuronal genes following AA treatment. The putative precursor cells were isolated from E13 rat ventral mesencephalons and expanded in the presence of bFGF. Cells were incubated in mitogen-free media supplemented with 200 microM AA or were left untreated as a control, and total RNA was isolated at different time points (expansion stage and 1, 3, and 6 days after induction of differentiation) and subjected to cDNA microarray analysis. Differentiation was evaluated by Western blot analysis and immunocytochemistry of neuron-specific markers. AA treatment of the mesencephalic precursors increased the expression of neuronal (MAP2) and astrocytic (glial fibrillary acidic protein) markers and the percentage of tyrosine hydroxylase (TH)-positive cells. The microarray analysis revealed that 12 known genes were up-regulated and 20 known genes were down-regulated in expansion-stage AA-treated cells. Six days after the induction of differentiation, AA-treated cells showed up-regulation of 48 known genes and down-regulation of 5 known genes. Our results identified several proteins, such as transferrin, S-100, and somatostatin, as being differentially regulated in AA-treated mesencephalic precursors. This novel result may lead to a better understanding of the molecular mechanisms underlying the AA-induced differentiation of mesencephalic precursors into DA neurons and may form the basis for improved DA neuronal production for treatment of Parkinson's disease patients.