Calcitriol modulates cholesteryl ester transfer protein (CETP) levels and lipid profile in hypercholesterolemic male rabbits: A pilot study.

Vitamin D3 efficacy against cardiovascular disease prevention has been reported in many experimental studies. We aimed to investigate the effect of the calcitriol or active form of Vitamin D3 (1, 25(OH) 2D3) on serum cholesteryl ester transfer protein (CETP) levels in a rabbit model of atherosclerosis. New Zealand white male rabbits were fed with 1% cholesterol diet and randomly assigned into two groups (n = 6). The case group was administrated with 50000 calcitriol (IU/kg/per wk) and the control group which administrated with calcitriol solvent (sesame oil) for 2 months. Then, after two months the lipid profile, CETP and 25OHD3 levels were measured. The serum concentration of CETP was increased after treatment with calcitriol in case group as compared to the control group (41.75 ± 3.19 vs. 34.5 ± 2.3, ng/ml, P < 0.05). We also observed higher levels of the 25OHD3 in the calcitriol group at the 1st month (16.3 ± 1.64 vs. 12.8 ± 1.33 ng/ml) and the 2nd month (19.5 ± 2.14 vs. 12.5 ± 1.25 ng/ml) as compared with the control group. the significant increase in the level of HDL-C was observed in the case group than the control group (P < 0.01). In addition, serum levels of LDL- Cholesterol (LDL-C), Triglyceride (TG) were reduced after assessment at 1st and 2nd month after administration of calcitriol. Our research indicated the significant anti-atherogenic effects of calcitriol in the rabbit model of atherosclerosis. However, increased in CETP levels by calcitriol may know as an additional way, which interfere with the anti-atherogenic effects of calcitriol.

Rosiglitazone, a PPARγ agonist, ameliorates palmitate-induced insulin resistance and apoptosis in skeletal muscle cells.

UNLABELLED: Palmitate induces insulin resistance and apoptosis in insulin target tissues. Rosiglitazone (RSG), a peroxisome proliferator-activated receptor γ (PPARγ) agonist, can activate both pro-apoptotic and anti-apoptotic pathways in different cells; however, its effect on palmitate-induced apoptosis in skeletal muscle cells remains to be elucidated. After differentiation of C2C12 cells, myotubes were treated with palmitate, RSG and GW9662 (PPARγ antagonist). MTT and terminal deoxynucleotide transferase dUTP nick end labelling (TUNEL) assays and caspase-3 activity were used to investigate the apoptosis. To study the underlying mechanism, glucose uptake, gene expression and protein levels were evaluated. A total of 0.75 mM palmitate reduced cell viability by 43% and increased TUNEL-positive cells and caspase-3 activity by 15-fold and 6.6-fold, respectively. RSG (10 µM) could markedly decrease the level of TUNEL-positive cells and caspase-3 activity in palmitate-treated cells. The protective effect of RSG on apoptosis was abrogated by GW9662. To investigate the molecular mechanism of this effect, gene expression and protein level of protein tyrosine phosphatase 1B (PTP1B) were evaluated. Palmitate and RSG individually increased the expression and protein level of PTP1B, whereas combined treatment (palmitate and RSG) were able to further increase the expression of PTP1B in C2C12 cells. We also evaluated the effect of RSG on palmitate-induced insulin resistance in muscle cells. RSG could significantly improve glucose uptake by 0.4-fold in myotubes treated with palmitate. Moreover, RSG could restore the phosphorylation of Akt in palmitate-treated cells. These data suggest that RSG protects skeletal muscle cells against palmitate-induced apoptosis and this effect appears to be mediated via the PPARγ-dependent and PTP1B-independent mechanisms. SIGNIFICANCE OF THE STUDY: Saturated free fatty acids (FFAs), such as palmitate, have been shown to induce cellular apoptosis. Strategies for preventing the cytotoxic effect of palmitate are useful in reduction of diabetes complications. In this study, we introduced RSG as an agent that protects skeletal muscle cells against palmitate-induced apoptosis and insulin resistance. It appears that RSG protects skeletal muscle cells against palmitate-induced apoptosis via the PPARγ-dependent and PTP1B-independent mechanisms. Given the role of FFAs in skeletal muscle apoptosis, these findings support the idea that RSG can ameliorate diabetes complications such as skeletal muscle loss.

S-Allylcysteine, a garlic compound, increases ABCA1 expression in human THP-1 macrophages.

ATP-binding cassette transporter A1 (ABCA1) is a key mediator of cholesterol efflux to apoA-I in lipid-loaded macrophages, which is the first step of reverse cholesterol transport in vivo and a critical step in preventing atherosclerosis. Enhanced ABCA1 expression may inhibit foam cell formation and consequently reduce atherogenic risk. The purpose of this study was to investigate the effect of S-allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract, on the expression of ATP-binding cassette transporter A1 in human THP-1 macrophages. The human monocyte THP-1 cells were differentiated to macrophage cells in the presence of phorbol 12-myristate13-acetate (PMA). Macrophage cells were then treated with different concentrations (10, 20 and 40 mM) of SAC for 24 h. Total RNA of treated macrophages was extracted and analyzed with real-time RT-PCR. ABCA1 protein expression was also analyzed with western blotting. Results showed that SAC increased the ABCA1 mRNA (1.82-, 2.07- and 2.23-fold) and protein (1.37-, 1.55- and 2.08-fold) expression in macrophage THP-1 cells compared with control (untreated cells). Results suggested that SAC can increase ABCA1 expression in macrophages and may be beneficial in promoting reverse cholesterol efflux.

The ENPP1 K121Q polymorphism is not associated with type 2 diabetes and related metabolic traits in an Iranian population.

The K121Q polymorphism of the ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been variably associated with insulin resistance and type 2 diabetes (T2D) in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that the K121Q variant might be associated with T2D and related metabolic traits in this population. The K121Q genotypes were determined by PCR-restriction fragment length polymorphism in 377 normoglycemic controls and 155 T2D patients. T2D patients had significantly higher values for systolic and diastolic blood pressure, BMI, glucose, cholesterol, triglyceride, LDL, apoB, insulin, and HOMA-IR, and lower levels of HDL than the normoglycemic subjects. The frequency of the Q allele did not differ between T2D and normoglycemic subjects (OR 0.96, 95% CI 0.90-2.00, P = 0.70). The Q allele frequency was 16.5% in T2D and 15.2% in normoglycemic subjects. The ENPP1 genotype (KQ + QQ) was not associated with the systolic and diastolic blood pressure, glucose, triglyceride, cholesterol, LDL-C and HDL-C, apo B, BMI, HOMA-IR, and insulin levels in both normoglycemic and T2D groups. Our results suggest that the ENPP1 121Q allele might not be associated with T2D and related metabolic traits among Iranian subjects.

The Preventive Effect of L-Lysine on Lysozyme Glycation in Type 2 Diabetes.

Lysozyme is a bactericidal enzyme whose structure and functions change in diabetes. Chemical chaperones are small molecules including polyamines (e.g. spermine), amino acids (e.g. L-lysine) and polyols (e.g. glycerol). They can improve protein conformation in several stressful conditions such as glycation. In this study, the authors aimed to observe the effect of L-lysine as a chemical chaperone on structure and function of glycated lysozyme. In this study, in vitro and in vivo effects of L-lysine on lysozyme glycation were investigated. Lysozyme was incubated with glucose and/or L-lysine, followed by an investigation of its structure by electrophoresis, fluorescence spectroscopy, and circular dichroism spectroscopy and also assessment of its bactericidal activity against M. lysodeikticus. In the clinical trial, patients with type 2 diabetes mellitus (T2DM) were randomly divided into two groups of 25 (test and control). All patients received metformin and glibenclamide for a three months period. The test group was supplemented with 3 g/day of L-lysine. The quantity and activity of lysozyme and other parameters were then measured. Among the test group, L-lysine was found to reduce the advanced glycation end products (AGEs) in the sera of patients with T2DM and in vitro condition. This chemical chaperone reversed the alteration in lysozyme structure and function due to glycation and resulted in increased lysozyme activity. Structure and function of glycated lysozyme are significantly improved by l-lysine; therefore it can be considered an effective therapeutic supplementation in T2DM, decreasing the risk of infection in these patients.

Lead concentration in breast milk of lactating women who were living in Tehran, Iran.

It is obvious that lead intake is of concern not for its beneficial/essential effects on metabolism, but rather for its toxic actions, which can be especially damaging to children. The objective of this study was to analyze the concentration of lead in milk of mothers during prolonged lactation. Milk samples from 43 mothers were collected at 2 months postpartum. Lead was analyzed using atomic absorption spectrophotometer. The value of lead in human milk was 23.66±22.43 µg/l. Lead concentration in human milk of mothers was higher than other countries and no significant relationship was found between levels of human milk lead and mother's education, age, parity, height and weight. The concentrations of lead in the milk samples were high, which makes a major public health hazard for the inhabitants, especially neonatal and children, of the industrial locations.

Amygdalin inhibits angiogenesis in the cultured endothelial cells of diabetic rats.

BACKGROUND: Angiogenesis contributes to different physiological and pathological conditions. The aim of this study was to investigate for the first time the antiangiogenic effects of amygdalin on the cultured endothelial cells of diabetic rats. MATERIALS AND METHODS: A total of 20 streptozotocin-induced diabetic rats were divided into two equal groups of control and amygdalin-treated animals. Eight weeks after the induction of diabetes, amygdalin was injected intraperitoneally (3 mg/kg) to the rats of the treatment group. One day later, rats were sacrificed; the aortic arteries were excised and cut as 2 mm rings. Each aortic ring was incubated in a cell-culture well for 7 days. The process of angiogenesis was monitored by counting the number of microvessels and primary microtubules in each well. RESULTS: Optic microscopy showed proliferation and migration of new endothelial cells to the fibrin gels. The endothelial cells produced primary microtubules which gradually made several branches and finally made a vascular matrix. The number of the primary microtubules and microvessels were significantly lower in the amygdalin-treated vs. control group (P < 0.01). CONCLUSION: Therefore, amygdalin exerts inhibitory effects on angiogenesis in aortic rings of diabetic rats and may pave a new way for treatment of unfavorable angiogenic conditions.

Effect of aqueous extract of Elaeagnus angustifolia fruit on experimental cutaneous wound healing in rats.

The present study was conducted to investigate the histological changes and wound healing effect of aqueous extract of Elaeagnus angustifolia. After creating full-thickness skin wounds on the back of 45 male Sprague-Dawley rats they were randomly divided into three groups. Treated group received the extract, positive control group were treated with mupirocin ointment 2% and control group did not receive any treatment. Wound healing rates were calculated on days 3, 5, 8, 10, 12 and 15 post-wounding and the wound tissues were harvested at 5, 10, and 15 days for histological analysis and hydroxyproline content measurement. The results indicated a significant increase in the percentage of wound contraction and hydroxyproline content in the treated group comparing to the control and positive control groups. A significant increase in the assigned histological scores was observed at 10 and 15 days in the treated and positive control groups compared to the control group. The results demonstrate that aqueous extract of Elaeagnus angustifolia accelerates cutaneous wound healing, and its effect may be due to the increased re-epithelialization and collagen deposition in wound and so it can be considered as a therapeutic agent for wound healing.