Metformin reverses the effects of high glucose on human dermal fibroblasts of aged skin via downregulating RELA/p65 expression

Journal of Physiology and Biochemistry - Metformin has been successfully used as an anti-aging agent but exact molecular mechanisms of metformin in anti-aging remain unknown. Hyperglycemia during...     

Genetic polymorphisms of estrogen receptor alpha and catechol-O-methyltransferase genes in Turkish patients with familial prostate carcinoma

OBJECTIVES:

Estrogen is one of the most crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. We evaluated the association between genetic polymorphisms in estrogen receptor alpha (ESR1) and catechol-O-methyltransferase (COMT) genes and the risk of developing familial prostate carcinoma.

MATERIALS AND METHODS:

In this study, 34 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 30 healthy age-matched male controls were enrolled. The genotypes of ESR1 and COMT genes were analyzed employing polymerase chain reaction-restriction fragment length polymorphism method. 34 cases with prostate carcinoma, whose first degree relatives had prostate carcinoma and 14 age-matched male controls were enrolled to analyze the genotype of these two genes.

RESULTS:

Among control patients, the ESR1 PvuII genotypes of C/C, C/T and T/T were observed in 37%, 26% and 37%, respectively, whereas the C/C, C/T and T/T genotypes were observed in 18%, 41% and 41% of case patients, respectively. Among controls, the ESR1 PvuII allele frequencies of C and T were equally observed, whereas the C and T allele frequencies were observed in 38% and 62% of patients, respectively. Among ESR1 PvuII genotypes there were not any significant difference in terms of genotype (P = 0.199) and allele (P = 0.181) frequencies. Among controls, the ESR1 XbaI genotypes of G/G, G/A and A/A were observed in 33%, 37% and 33%, respectively, whereas the G/G, G/A and A/A genotypes were observed in 12%, 47% and 41% of patients, respectively. Among controls, the ESR1 XbaI allele frequencies of A and G were observed equally, respectively, whereas the A and G frequencies were observed in 65% and 35% of patients, respectively. Among ESR1 Χ baI, there was not any significant difference in terms of genotype (P = 0.111) and allele (P = 0.093) frequencies. But the C/C genotype of the PvuII site and G/G genotype of the XbaI site in the ESR1 gene were associated significantly with the risk of developing prostate carcinoma. The G/G, G/A and A/A genotypes of the COMT gene were observed in 50%, 29% and 21% of control patients and in 53%, 21% and 26% of case patients, respectively. The A and G allele frequencies of the COMT gene were observed in 36.7%, 63.3% of control patients and in 36.8%, 63.2% of case patients, respectively. In COMT gene, there was not any significant difference in terms of genotype (P = 0.843) and allele (P = 0.991) frequencies. But the G/A genotype of the COMT gene had a weak tendency toward increased risk.

CONCLUSION:

Polymorphisms of ESR1 gene in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma.     

Protective effects of antioxidant combination against D‐galactosamine‐induced kidney injury in rats

The protective effects of an antioxidant combination in kidney injury induced by the injection of D‐galactosamine (D‐GaIN) were examined in the present study. Sprague Dawley female rats were used and divided into four groups as follows: (1) animals injected physiological saline solution, intraperitoneally, (2) animals treated with the combination of ascorbic acid (100 mg kg^?1 day^?1), β‐carotene (15 mg kg^?1 day^?1), α‐tocopherol (100 mg kg^?1 day^?1), and sodium selenate (0.2 mg kg^?1 day^?1) for three days orally, (3) rats injected D‐GaIN (500 mg kg^?1) intraperitoneally as a single dose, and (4) animals treated with the antioxidant combination for three days, then injected D‐GaIN. The tissue and blood samples of animals were collected for morphological and biochemical evaluations. Histopathological injury in kidney tissues was observed together with a significant increase in tissue lipid peroxidation (LPO) level, myeloperoxidase (MPO), lactate dehydrogenase, catalase and superoxide dismutase (SOD) activities, and serum creatinine and urea levels, and a significant decrease in glutathione level and glutathione peroxidase activity in D‐GaIN injected rats. However, a decrease in the degenerative changes was detected in the kidney tissue of D‐GaIN + antioxidant group, and biochemical results showed reversed effects. In conclusion, it seems reasonable to conclude that the treatment of the antioxidant combination has a protective effect on D‐GaIN‐induced kidney injury of rats. Copyright © 2010 John Wiley & Sons, Ltd.     

Combination of Selenium and Three Naturally Occurring Antioxidants Administration Protects d-Galactosamine-Induced Liver Injury in Rats

d-Galactosamine (d-GaIN) is a highly selective hepatotoxin that causes liver injury similar to human viral hepatitis via depletion of uridine nucleotides, which subsequently diminishes synthesis of RNA and proteins. The aim of this study was to investigate the role of selenium, ascorbic acid, beta-carotene, and alpha-tocopherol on d-GaIN-induced liver injury of rats by morphological and immunohistochemical means. In this study, Sprague–Dawley female rats were divided into four groups. Group I consists of rats injected physiologic saline solution intraperitoneally. Group II consists of rats given selenium (0.2 mg/kg per day), ascorbic acid (100 mg/kg per day), beta-carotene (15 mg/kg per day), and alpha-tocopherol (100 mg/kg per day) for 3 days via gavage method. Group III consists of the single dose of d-GaIN (500 mg/kg)-injected animals. Group IV are the d-GaIN-injected animals given the same antioxidant combination. In situ terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate nick-end labeling (TUNEL) assay was applied to determine apoptosis for paraffin sections of the liver samples. Moreover, caspase-3 and proliferating cell nuclear antigen antibody were applied for paraffin sections. In the group given d-GaIN, apoptotic cells with TUNEL assays and caspase-3 activity, which are liver injury markers induced by d-GaIN, the hepatocyte proliferation with cell proliferation assay increased. However, selenium and other three antioxidants combination clearly suppressed an increase in apoptotic cells with TUNEL assay and caspase-3 activity. In addition, it suppressed d-GaIN-induced cell proliferation in the liver. As a result, these results indicate that selenium and three naturally occurring antioxidants shows a protective effect against liver injury induced by d-GaIN. These results suggest that supplementation with the combination of selenium, ascorbic acid, beta-carotene, and alpha-tocopherol may help prevent the development of liver injury.     

Visfatin Levels in Subclinical Hypothyroidism

Alterations in thyroid function are associated with changes in body weight, metabolism, and low-grade inflammation abnormal thyroid function may be associated with disturbances in the production of adipokines also. Although there have been studies showing changes in visfatin levels in thyroid dysfunction, exact relationship between them was still unclear. Our aim was to evaluate serum concentrations of visfatin in patients with subclinical thyroid dysfunction before and after normalization of thyroid function tests. The study included 43 patients (mean age 50.1 ± 10.6 years) with subclinical hypothyroidism. Serum insulin, visfatin, TSH, free T4 (FT4) and free T3 (FT3) levels of subjects were analyzed. Visfatin levels were measured in all patients before starting therapy and after normalization of thyroid function. Serum visfatin levels of subclinical hypothyroid patients were 0.99 ± 0.45 and they were similar after normalization of thyroid function (p = 0.394). Serum visfatin levels were negatively correlated with FT4 levels before treatment (r = ?0.329 p < 0.05). There was no significant correlation between serum levels of visfatin and the serum levels of TSH and FT3. Serum visfatin levels did not correlate with insulin, fasting blood glucose, total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride levels. In this study, it was shown visfatin levels did not change after replacement therapy in patients with subclinical hypothyroidism. Subclinical hypothyroid state may be an earlier stage regarding the changes of adipocytokines specifically the visfatin secretion as seen in overt hypothyroidism.     

The Interaction Between Helicobacter pylori and Atopy: Does Inverse Association Really Exist?

Aim: To date, cross‐sectional and case–control studies suggest an inverse association between Helicobacter pylori infection and atopic diseases, whereas the immunologic basis has not been studied yet. In this study we investigated T helper (Th) cell function in H. pylori‐infected children and compared cytokine responses in atopic and non‐atopic groups. Methods: The study groups was recruited from a cohort of 327 healthy children evaluated and followed‐up for 6 years to assess the natural history of H. pylori infection. Seventy‐four of 136 healthy children who underwent ¹³C urea breath test were eligible and accepted to participate. All participants were evaluated by a questionnaire, and skin‐prick testing. According to the results, children were divided into four groups with respect to the presence or absence of H. pylori and atopy. Peripheral blood mononuclear cells isolated from 34 of 74 children were cultured with H. pylori, Der p 1, and phytohemagglutinin (PHA). Interferon‐gamma (IFN‐γ), interleukin (IL)‐4 and IL‐10, transforming growth factor‐beta (TGF‐β) levels were measured in supernatants. Results: The frequency of atopy was lower in H. pylori‐infected group (31.9% vs. 48.1, p = .22), while atopic symptoms were similar between infected and non‐infected children. While PHA and H. pylori induced IFN‐γ levels were significantly higher in H. pylori‐infected children, concomitant presence of both atopy and H. pylori decreased the level of PHA and H. pylori induced IFN‐γ production. PHA and Der p 1‐induced IL‐4 levels were higher in atopic children, and IL‐4 production was suppressed when they were concomitantly infected with H. pylori. The production of TGF‐β was found to be suppressed in atopic children irrespective of the presence of H. pylori infection. Conclusion: The results of the current study demonstrated a counteractive Th1 and Th2 cytokine interaction between H. pylori infection and atopy. However, this counteractive immunologic balance did not protect against atopy.     

The effects of vitamins and selenium mixture against brain tissue induced by d‐galactosamine

Brain damage is a major complication of fulminant hepatic failure. d ‐Galactosamine (d ‐GalN)‐induced liver toxicity causes damage to brain. The effects of vitamins and selenium mixture against d ‐GalN stimulated brain injury were investigated in this study. Sprague‐Dawley female rats aged 2.0‐2.5 months were used for the study. The rats were divided into four categories. A 0.9% NaCl solution was intraperitoneally given to the experimental rats in the first group. Using gavage technique, the second group of animals were subjected to a formulation consisting of 100 mg·kg^?1·day^?1 vitamin C, 15 mg·kg^?1·day^?1 of β‐carotene, 100 mg·kg^?1·day^?1 of α‐tocopherol in addition to 0.2 mg·kg^?1·day^?1 of sodium selenate for 3 days. The third group was given a single dose of d ‐GalN hydrochloride at the concentration of 500 mg·kg^?1 through a saline injection. The final group was given similar concentrations of both the antioxidant combination and d ‐GalN. Tissue samples were collected under ether anesthesia. The rats treated with d ‐GalN showed brain damage; increased myeloperoxidase, catalase, glutathione peroxidase, glutathione‐S‐transferase, lactate dehydrogenase, and superoxide dismutase activities; and decreased glutathione levels. Treatment with vitamins and selenium combination resulted in alleviation of these alterations in the rats. These findings suggest that administration of the vitamins and selenium combination suppresses oxidative stress and protects brain cells from injury induced by d ‐GalN.