Xu J

Resveratrol reduces vascular cell senescence through attenuation of oxidative stress by SIRT1/NADPH oxidase-dependent mechanisms

OBJECTIVEnSenescence of vascular cells contributes to the development of cardiovascular diseases and the overall aging. This study was undertaken to investigate the effects of resveratrol (Res) on amelioration of vascular cell aging and the role of SIRT1/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase pathway.nnnMETHODS AND RESULTSnAdult male Wistar rats were treated with a high-fat/sucrose diet (HFS) in the presence or absence of Res for 3 months. HFS and in vitro treatment with high glucose increased the senescence cells and reactive oxygen species production in rat aorta and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Res protected against HFS- or high-glucose-induced increase in NADPH oxidase p47phox expression and decrease in SIRT1 level. Apocynin, a NADPH oxidase inhibitor, down-regulated p47phox protein expression, but had no influence on SIRT1 protein; sirtinol, a SIRT1 inhibitor, aggravated the decrease in SIRT1 protein level and the increase in p47phox protein expression induced by high glucose.nnnCONCLUSIONnOur studies suggested that Res was able to reverse the senescence process in aorta induced by HFS in rats or induced by the exposure to high glucose in cultured BAECs. The underlying mechanism is at least SIRT1/NADPH oxidase pathway dependent.

Alteration of Lipid Profile in Subclinical Hypothyroidism: A Meta-Analysis

Background Previous studies yielded controversial results about the alteration of lipid profiles in patients with subclinical hypothyroidism. We performed a meta-analysis to investigate the association between subclinical hypothyroidism and lipid profiles. Material/Methods We searched PubMed, Cochrane Library, and China National Knowledge Infrastructure articles published January 1990 through January 2014. Dissertation databases (PQDT and CDMD) were searched for additional unpublished articles. We included articles reporting the relationship between subclinical hypothyroidism and at least 1 parameter of lipid profiles, and calculated the overall weighted mean difference (WMD) with a random effects model. Meta-regression was used to explore the source of heterogeneity among studies, and the Egger test, Begg test, and the trim and fill method were used to assess potential publication bias. Results Sixteen observational studies were included in our analysis. Meta-analysis suggested that the serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and total triglyceride levels were significantly increased in patients with subclinical hypothyroidism compared with euthyroidism individuals; the WMD were 12.17 mg/dl, 7.01 mg/dl, and 13.19 mg/dl, respectively (P<0.001 for all). No significant difference was observed for serum high-density lipoprotein cholesterol (HDL-C). Match strategy was the main source of heterogeneity among studies in TC and LDL-C analysis. Potential publication bias was found in TC and LDL-C analysis by the Egger test or Begg test and was not confirmed by the trim and fill method. Conclusions Subclinical hypothyroidism may correlate with altered lipid profile. Previous studies had limitations in the control of potential confounding factors and further studies should consider those factors.

Excess Iodine and High-Fat Diet Combination Modulates Lipid Profile, Thyroid Hormone, and Hepatic LDLr Expression Values in Mice

The aim of this study was to illustrate the combined effect of excess iodine and high-fat diet on lipid metabolism and its potential molecular mechanism. Sixty Balb/c mice were randomly allocated to three control groups or three excess iodine groups and fed with a high-fat diet in the absence or presence of 1,200xa0μg/L iodine for 1, 3, or 6xa0months, respectively. Serum lipid parameters and serum thyroid hormones were measured. Expressions of scavenger receptor class B type-I (SR-BI) and low density lipoproteins receptor (LDLr) mRNA and protein in liver were detected. Thyroid histology and liver type 1 iodothyronine deiodinase activity were analyzed. At the end of 3 and 6xa0months, compared with control, serum TC, TG, and LDL-C in excess iodine group were significantly lower (pu2009<u20090.05). LDLr expression in liver was increased significantly (pu2009<u20090.05) and parallel to the change of serum TC and TG. TT3 and TT4 levels in serum were elevated and TSH decreased significantly (pu2009<u20090.05). Liver type I iodothyronine deiodinase activity was significantly higher (pu2009<u20090.05) than control at the end of 6xa0months. Moreover, a time course damage effect of excess iodine combined with high-fat diet on thyroid glands was observed. The present findings demonstrated that excess iodine combined with high-fat diet could cause damage to thyroid glands and lead to thyroid hormone disorder. Those in turn caused the upregulation of hepatic LDLr gene, which resulted in the disorder in serum lipids.

Supplemental Selenium Alleviates the Toxic Effects of Excessive Iodine on Thyroid

As excessive iodine intake is associated with a decrease of the activities of selenocysteine-containing enzymes, supplemental selenium was hypothesized to alleviate the toxic effects of excessive iodine. In order to verify this hypothesis, Balb/C mice were tested by giving tap water with or without potassium iodate and/or sodium selenite for 16xa0weeks, and the levels of iodine in urine and thyroid, the hepatic selenium level, the activities of glutathione peroxidase (GSHPx), type 1 deiodinase (D1), and thyroid peroxidase (TPO) were assayed. It had been observed in excessive iodine group that hepatic selenium, the activities of GSHPx, D1, and TPO decreased, while in the groups of 0.2xa0mg/L, 0.3xa0mg/L and 0.4xa0mg/L supplemental selenium, the urinary iodine increased significantly. Compared with the group of excessive iodine intake alone, supplemental selenium groups had higher activities of GSHPx, D1, and TPO. We could draw the conclusion that supplemental selenium could alleviate toxic effect of excessive iodine on thyroid. The optimal dosage of selenium ranges from 0.2 to 0.3xa0mg/L which can protect against thyroid hormone dysfunction induced by excessive iodine intake.

Iodine Excess Induces Hepatic Steatosis Through Disturbance of Thyroid Hormone Metabolism Involving Oxidative Stress in BaLB/c Mice

Iodine excess is emerging as a new focus. A better understanding of its hazardous effects on the liver will be of great benefit to health. The aim of this study is to illustrate the effects of iodine excess on hepatic lipid homeostasis and explore its possible mechanisms. One hundred twenty BaLB/c mice were given iodine at different levels (0, 0.3, 0.6, 1.2, 2.4, and 4.8xa0mg I/L) in drinking water for 1 or 3xa0months. Lipid parameters and serum thyroid hormones were measured. Hepatic type 1 deiodinase activity and oxidative stress parameters were evaluated. The mRNA expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) was detected by real-time polymerase chain reaction. Dose-dependent increase of hepatic triglyceride content was detected (ru2009=u20090.680, Pu2009<u20090.01) in iodine-loaded groups. Evident hepatic steatosis was observed in 2.4 and 4.8xa0mg I/L iodine-loaded groups. The activities of antioxidant enzymes (glutathione peroxidase and superoxide dismutase) were decreased, and the malondialdehyde level was increased by excessive iodine in both serum and liver in a dose-dependent manner, accompanying the decrease of hepatic D1 activity. That resulted in the increase of serum total thyroxine and the decrease of serum total triiodothyronine in iodine-loaded groups. The mRNA expression of SREBP-1c and FAS was increased in iodine-loaded groups in response to the change of serum triiodothyronine. Present findings demonstrated that iodine excess could dose dependently induce hepatic steatosis. Furthermore, our data suggested that the disturbance of thyroid hormone metabolism involving oxidative stress may play a critical role in iodine excess-induced hepatic steatosis.

Dose and time-dependent hypercholesterolemic effects of iodine excess via TRβ1-mediated down regulation of hepatic LDLr gene expression

BackgroundWith the global improvement of iodine nutrition, iodine excess is emerging as a new concern.Aim of studyThe aim of this study is to illustrate the physiological effects and potential molecular mechanisms of excessive iodine intake on lipid metabolism.MethodsBalb/c mice were given drinking water containing different levels of iodine for 1xa0month and treated with 1.2xa0μg/mL iodine for different periods of time, respectively. Plasma lipid parameters and serum thyroid hormones were measured. Expressions of hepatic genes were detected by real-time polymerase chain reactions and Western blot.ResultsDose-dependent hypercholesterolemic effects were detected in mice (TC, rxa0=xa00.615; pxa0<xa00.01). Drinking 1.2xa0μg/mL iodine water for 1xa0month had no significant effect on serum lipid metabolism, while prolonged exposure induced an increase of serum cholesterol. Serum thyroid hormones were not affected by iodine throughout the study. At the molecular level, we detected a dose-dependent attenuation of hepatic low density lipoprotein receptor (LDLr) and thyroid hormone receptor β1 (TRβ1) expression in parallel to the change of serum cholesterol. Treatment with 1.2xa0μg/mL iodine water for 1xa0month did not affect LDLr and TRβ1 expression, while 3 or 6xa0months exposure resulted in a decrease of their expression.ConclusionPresent findings demonstrated dose- and time-dependent hypercholesterolemic effects of iodine excess. Furthermore, our data suggests that TRβ1-mediated down regulation of hepatic LDLr gene may play a critical role in iodine excess-induced hypercholesterolemic effects.

Oral vitamin D supplementation has a lower bioavailability and reduces hypersecretion of parathyroid hormone and insulin resistance in obese Chinese males.

OBJECTIVEnTo examine the vitamin D status, SNP of the vitamin D receptor gene (VDR) and the effects of vitamin D supplementation on parathyroid hormone and insulin secretion in adult males with obesity or normal weight in a subtropical Chinese city.nnnDESIGNnAn intervention trial.nnnSETTINGnShenzhen City, Guangdong Province, China.nnnSUBJECTSnFrom a cross-sectional survey conducted from June to July, eighty-two normal-weight and ninety-nine obese males (18-69 years) were screened to analyse their vitamin D status and for five SNP of VDR. From these individuals, in the same season of a different year, obese and normal-weight male volunteers (twenty-one per group) were included for an intervention trial with oral vitamin D supplementation at 1250 µg/week for 8 weeks.nnnRESULTSnFor the survey, there was no significant difference (P>0·05) in baseline circulating 25-hydroxyvitamin D concentrations or in the percentages of participants in different categories of vitamin D status between the two groups. The VDR SNP, rs3782905, was significantly associated with obesity (P=0·043), but none of the examined SNP were correlated with serum 25-hydroxyvitamin D when adjusted for age, BMI and study group. After vitamin D supplementation, serum 25-hydroxyvitamin D concentration, hypersecretions of parathyroid hormone and insulin, and insulin resistance in the obese were changed beneficially (P<0·05); however, the increase in serum 25-hydroxyvitamin D was less than that of the normal-weight men.nnnCONCLUSIONSnFor obese and normal-weight men of subtropical China, the summer baseline vitamin D status was similar. However, oral vitamin D supplementation revealed a decreased bioavailability of vitamin D in obese men and ameliorated their hypersecretion of parathyroid hormone and insulin resistance.

Analysis of trans-resveratrol and trans-piceid in vegetable foods using high-performance liquid chromatography.

Abstract Trans-resveratrol and resveratrol glucoside are natural phenolic compounds existed in a wide variety of plant species, which are extensively consumed in many countries. The existing studies excessively focused on grapes and their products, and little about daily vegetable foods. Actually, in much more countries, vegetable foods are residents’ principal food and nutrient origins. This study was to investigate the levels of trans-resveratrol and trans-piceid in daily vegetable foods of China using high-performance liquid chromatography (HPLC) method with fluorescence detection (FLD). Trans-piceid was the major form existing in most vegetable foods, and most of the samples contained higher trans-piceid than trans-resveratrol. The contents of trans-resveratrol and trans-piceid in different varieties and regions were different. Moreover, peculiar vegetable foods to some region were also one of the most important sources of trans-resveratrol and trans-piceid. Therefore, vegetable foods were other significant sources of trans-resveratrol and trans-piceid except the foods published.

Selenium supplement alleviated the toxic effects of excessive iodine in mice

The relationship between the iodine intake level of a population and the occurrence of thyroid diseases is U-shaped. When excessive iodine is ingested, hypothyroidism or hyperthyroidism associated with goiter might develop. The aim of the study was to evaluate the effect of Se supplementation on the depression of type 1 deiodinase (D1) and glutathione peroxidase (GSHPx) activities caused by excessive iodine. D1 activity was assayed by the method with 125I-rT3 as a substrate. Compared to the effect of iodine alone, iodine in combination with selenium increased the activities of D1 and GSHPx. The addition of selenium alleviated the toxic effects of iodine excess on the activities of D1 and GSHPx.

Effect of selenium on thyroid hormone metabolism in filial cerebrum of mice with excessive iodine exposure

The effects of supplementing selenium on thyroid hormone metabolism were studied on mice with excessive iodine exposure. The serum concentrations of thyroxine (T4) and triiodothyronine (T3) and the activities of iodothyronine 5′ and 5-deiodinase (D2, D3) were measured in the brain of filial mice to study the influence of selenium on thyroid hormone metabolism. Measurements were carried out on postnatal day 0, 14, and 28. It was found that selenium supplementation alleviated the adverse effects of excessive iodine on progeny. The serum TT4 level as well as TT4 and TT3 concentrations and D3 activity in cerebrum of progeny decreased, whereas D2 activity increased in the cerebrum of progeny on postnatal day 0 and 14. Selenium supplementation exerted some favorable effects on thyroid hormone metabolism in cerebrum of progeny of dam with excessive iodine intake.