Synthesis of new indole-2-carboxamide and 3-acetamide derivatives and evaluation their antioxidant properties.

In recent years, antioxidant compounds play an important role as a health-protecting factor. Antioxidants protect cells against the damaging effects of reactive oxygen species (ROS). An imbalance between antioxidants and ROS results in oxidative stress, which leads to cellular damage and it is linked to many vital diseases. It was shown that heme oxygenase (HO) provides efficient cytoprotection against oxidative stress. In this study, a series of indole-2-carboxamide and 3-acetamide derivatives was tested for in vitro effects on HO activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition. Among the synthesized compounds, N-[3-(dimethylamino)propyl]-1H-indole-2-carboxamide 3 was found as the most activator of HO and N-(2-(dimethylamino)ethyl)-2-(1H-indol-3-yl)acetamide 8 was found the most potent inhibitor for DPPH at 10(-4) M concentration.

Effects of varying degrees of partial bladder outlet obstruction on urinary bladder function of rats: A novel link to inflammation, oxidative stress and hypoxia.

OBJECTIVES: The aim of the present study was to investigate the effects of different degrees of obstruction, and the roles of inflammation, oxidative stress, and hypoxia parameters on bladder function. METHODS: Thirty male Sprague-Dawley rats were divided into 3 groups (n = 10 in each group): (i) sham-operated control; (ii) severe partial bladder outlet obstruction (PBOO); and (iii) moderate PBOO. Severe and moderate PBOO were induced by urethral ligation using 3-Fr and 4-Fr catheters, respectively, for 6 weeks. After 6 weeks, the in vitro contractile responses to carbachol, electrical field stimulation, ATP and KCl were measured in bladder strips. In addition, mRNA and protein expression of nuclear factor kappa B (NF-κB) hypoxia-inducible factor (HIF) and nuclear factor, erythroid 2-like 2 (Nrf2) in bladder were determined by real-time polymerase chain reaction and western blotting. Malondialdehyde (MDA) levels in bladder tissues were also determined. RESULTS: Rats in the severe PBOO group had the highest bladder weight. Detrusor strips from rats in the severe PBOO group exhibited 61%-82% smaller contractile responses to all four stimuli than those from the sham-operated group. Activity of NF-κB as an inflammatory marker was increased in the severe PBOO group, whereas HIF-1α and HIF-2ß protein levels were increased significantly in the moderate PBOO group. A master regulator of oxidative stress, Nrf2 expression was increased in all obstructed rats. MDA levels were higher in the severe PBOO group than in sham-operated group. CONCLUSION: The results of the present study reveal the importance of oxidative stress-induced NF-κB signaling in bladder dysfunction with severe obstruction. Altered HIF signaling may contribute to the functional impairment after PBOO. Novel and evolving therapies targeting oxidative and/or inflammatory pathways may be a reasonable strategy for the management of lower urinary tract symptoms or benign prostatic hyperplasia.

Evaluation of Antioxidant Activities and Phenolic Compounds of Scorzonera latifolia (Fisch. & Mey.) DC. Collected from Different Geographic Origins in Turkey.

OBJECTIVES: The chemical composition of plants is considered to be affected by many parameters. Therefore, the region where the samples are collected is likely to have an influence on the composition of phenolic compounds, so that their biological activities. In the present study, evaluation of antioxidant activity potentials of Scorzonera latifolia (Fisch. & Mey.) DC. aerial parts and roots, which were collected from different regions of Turkey, was aimed. MATERIALS AND METHODS: 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method and measurement of malondialdehyde (MDA) levels were used for determining antioxidant capacities of the tested extracts. In order to observe variations in the chemical composition of the investigated samples qualitatively as well as quantitatively, high performance liquid chromatography analyses were performed. RESULTS: Quantitative analysis showed that the amounts of chlorogenic acid and hyperoside in plants vary according to the regions where the samples were collected. As a result aerial parts of the S. latifolia collected from the Kars region have found to contain higher amount of chlorogenic acid (1246.78±3.20 µg/g) as well as hyperoside (652.32±2.48 µg/g) than other samples. The highest DPPH radical scavenging activity was determined with the IC50 value of 1.036 mg/mL for S. latifolia aerial parts of Kayseri sample. MDA level was detected as the lowest with treatment of S. latifolia Bayburt root sample (4.41 nmol/mL). CONCLUSION: According to the antioxidant activity results, no significant difference was observed in the antioxidant potential between the samples collected from different locations except for S. latifolia collected from the Kars region.

Gold nanoparticle-lignan complexes inhibited MCF-7 cell proliferation in vitro: a novel conjugation for cancer therapy.

Nanoparticles, including gold nanoparticles (AuNP), have been used in imaging in cancer treatment and as therapeutic agents and drug delivery vehicles. Particularly lignans, also called phytoestrogens, have strong effects on the treatment of carcinomas due to their antiestrogenic, antiangiogenic and proapoptotic mechanism. The aim of this study is to investigate the antiproliferative effects of three lignans-AuNP conjugates, pinoresinol (PINO), lariciresinol (LARI) and secoisolariciresinol (SECO), on the MCF-7 cell lines. For this purpose, first, thiolated ß-cyclodextrin (ß-CD) was synthesized to achieve a surface modification of AuNP, and then the ß-CD modified AuNP was characterized using the transmission electron microscopy (TEM), UV-Visible and Nuclear Magnetic Resonance (NMR) spectroscopy. Then, the selected lignans were conjugated to the ß-CD-modified AuNP, and the antiproliferative effect of these conjugates was monitored. The results suggest that when compared to their non-conjugated forms, the AuNP-bound lignan conjugates prevented the proliferation of the MCF-7 cells significantly. Therefore, these AuNP-conjugated derivatives can be new candidate agents for breast cancer therapy.

Annexin V expression and anti-annexin V antibodies in type 1 diabetes.

BACKGROUND: Annexin V (AnxV) has potent anticoagulant properties and regulatory functions for apoptosis and inflammation. Antibodies against annexin V (anti-AnxVs) may inhibit AnxV functions, leading to thrombosis during autoimmune diseases. Type 1 diabetes is an autoimmune disease and related with an ongoing autoimmune inflammation and thrombotic complications. There is no study evaluating anti-AnxVs/AnxV in a disease setting. OBJECTIVE: The aim of this study was to evaluate the status of AnxV and anti-AnxVs in patients with type 1 diabetes. METHODS: One hundred twenty-one patients with type 1 diabetes and 92 healthy controls were included in this study. Serum levels of AnxV and anti-AnxVs and expression of the AnxV gene and its common polymorphism in Kozak sequence (-1C>T) were studied. As a functional assay, the binding capacity of AnxV to platelets was evaluated. RESULTS: As compared with controls, type 1 diabetic patients had significantly low serum AnxV levels and AnxV gene expression. The number of anti-AnxV positivity and their serum levels were significantly higher in type 1 diabetic patients than controls. AnxV binding to platelets were significantly decreased in the type 1 diabetic patients. The frequencies of the -1C>T polymorphism of AnxV gene did not differ between groups. CONCLUSIONS: This study demonstrated the significant changes in AnxV levels and its function in type 1 diabetic patients. These results support the hypothesis that the defective AnxV system may have a role in ongoing autoimmune activity and the development of thrombotic complications in type 1 diabetes. Further studies are necessary to elucidate the clinical impact of anti-AnxVs and dysregulated AnxV function in type 1 diabetes.

Changes in oxidative stress in renal graft patients receiving calcineurin inhibitors: cyclosporine versus tacrolimus.

OBJECTIVES: The effects of calcineurin inhibitors on oxidative stress after renal transplant are obscure. This study sought to investigate the changes in plasma oxidative stress and lipid levels in patients receiving cyclosporine or tacrolimus before and after renal transplant for 6 months. MATERIALS AND METHODS: Twenty-one patients and 15 healthy controls were involved in our study. Twelve of the patients were treated with cyclosporine and 9 were treated with tacrolimus. Plasma malondialdehyde, nitrite/nitrate, vitamin C, vitamin E, and plasma glutathione levels, as well as total cholesterol and triglyceride levels, were evaluated before and after transplant for 6 months. RESULTS: Before the transplant, patients had higher malondialdehyde and plasma glutathione levels than did healthy controls (3.76 ± 0.79 nmol/mL vs 3.21 ± 0.57 nmol/mL; P < .05, and 66.6 ± 23.2 µmol/L vs 43.3 ± 26.9 µmol/L; P < .05). In the overall group of patients, a significant increase in malondialdehyde levels was detected 3 and 6 months after transplant (3.76 ± 0.79 nmol/mL vs 4.38 ± 0.87 nmol/mL in the third month; P = .02; and 3.76 ± 0.79 nmol/mL vs 4.28 ± 0.69 nmol/mL in the sixth month; P = .04). A significant reduction in plasma glutathione levels 1 month after transplant and nitrite/nitrate levels 6 months after transplant was found. No changes in vitamin C and vitamin E levels were detected before and after transplant. After 3 and 6 months of transplant, cyclosporine-treated patients had higher levels of total cholesterol and triglycerides when compared with tacrolimus-treated patients. CONCLUSIONS: An enhancement in plasma malondialdehyde levels was found after transplant at 6-month follow-up. However, no significant change in vitamin C, vitamin E, nitrite/nitrate levels between patients and controls was recorded. Although both calcineurin inhibitors showed similar effects on oxidative stress, cyclosporine-treated patients had higher levels of total cholesterol and triglycerides.

Diabetes-induced decrease in rat brain microsomal Ca2+-ATPase activity.

The Ca(2+)-ATPase activity of rat brain microsomes was studied in streptozotocin (STZ)-induced diabetes. Male rats, 200-250 g, were rendered diabetic by injection of STZ (45 mg kg(-1) body weight) via the teil vein. Brain tissues were collected at 1, 4 and 10 weeks after diabetes was induced for determination of Ca(2+)-ATPase activity, lipid peroxidation and tissue calcium levels. Diabetic rats had significantly elevated blood glucose levels compared to controls. Blood glucose levels were 92.92 +/- 1.22 mg dl(-1) (mean +/- SEM) for the control group, 362.50 +/- 9.61 mg dl(-1) at 1 week and >500 mg dl(-1) at 4, 8 and 10 weeks for the diabetics. Enzyme activities were significantly decreased at 1, 4, 8 and 10 weeks of diabetes relative to the control group (p < 0.001). Ca(2+)-ATPase activity was 0.084 +/- 0.008 U l(-1), 0.029 +/- 0.005 U l(-1), 0.029 +/- 0.006 U l(-1), 0.033 +/- 0.003 U l(-1) and 0.058 +/- 0.006 U l(-1) (mean +/- SEM) at control, 1, 4, 8 and 10 week of diabetes respectively. The change in calcium levels in diabetic rat brain at 8 and 10 weeks of diabetes was significantly higher than that of the control group (p < 0.05). On the other hand lipid peroxidation measured as TBARS (thiobarbituric acid reactive substances) was significantly higher at 8 and 10 weeks of diabetes (p < 0.05). The increase in lipid peroxidation observed in diabetic rat brain may be partly responsible for the decrease in calcium ATPase activity.