Ameliorative effects of gallic acid,quercetin and limonene on urethane-induced genotoxicity and oxidative stress in Drosophila melanogaster

The main objective of our present work was to ascertain the efficacy of Drosophila melanogaster model for assessing antigenotoxic and antioxidant effects of dietary phytochemicals gallic acid (GA), quercetin (QC) and limonene (Lim) against urethane (URE), a genotoxic environmental carcinogen. Oregon-K (ORK) adult male flies were fed GA, QC and Lim in combination with URE (20?mM) in 10% sucrose for 72?h. Third instar larvae were fed instant medium containing the above phytochemicals and URE for 24?h. Sex-linked recessive lethal (SLRL) test and assays for estimating glutathione content (GSH), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (MDA content) were performed. Adult feeding experiments demonstrated that co-treatment of flies with URE and the test phytochemicals has significantly decreased the frequencies of SLRL mutations in all the germ cell stages when compared to that with URE alone. Larval feeding experiments also showed a similar pattern. The above results correlate well with antioxidative potentials of the test agents where we observed the elevated enzymatic levels with a significant reduction in MDA level in Drosophila larvae. The results further suggest that the dietary phytochemicals have an antioxidant and antimutagenic property which can be assessed using D. melanogaster.     

The relationship between nutritional status,vitamin A and zinc levels and oxidative stress in patients with ataxia-telangiectasia

BackgroundAtaxia-telangiectasia (A-T) is a rare and degenerative disease that leads to varying degrees of immunodeficiency, oxidative stress, and malnutrition. Vitamin A and zinc are essential for immune function and antioxidant defence.ObjectiveTo compare levels of retinol, beta carotene, and zinc in patients with ataxia-telangiectasia and healthy controls.MethodsWe performed a cross-sectional study with 14 AT patients and 14 healthy controls matched for age and gender. All participants underwent a nutritional and laboratory evaluation comprising concentrations of retinol, beta carotene, serum and erythrocyte zinc, malondialdehyde (MDA), T lymphocyte numbers (CD4⁺ and CD8⁺) and immunoglobulin (IgA).ResultsThe AT patients showed high rates of malnutrition with reduced lean body mass when compared to the control group. However, the concentrations of MDA, retinol, beta carotene, and serum and erythrocyte zinc in AT patients were similar to those of the control group. The retinol levels presented a negative correlation with MDA and positive correlation with IgA serum level.ConclusionsThe AT patients assessed showed no change in nutritional status for vitamin A and zinc; however, they presented severe impairment in overall nutritional status observed and correlation between retinol with MDA and IgA.     

Felbamate produces antidepressant‐like actions in the chronic unpredictable mild stress and chronic social defeat stress models of depression

Felbamate is an anticonvulsant used in the treatment of epilepsy. In this study, we investigated the antidepressant‐like actions of felbamate in mice. The effects of felbamate were first assessed using the forced swimming test (FST) and tail suspension test (TST), and then investigated in the chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models of depression. The changes in the hippocampal brain‐derived neurotrophic factor (BDNF) signaling cascade after chronic stress and felbamate treatment were also examined. It was found that felbamate exhibited antidepressant‐like activities in the FST and TST without affecting the locomotor activity of mice. Felbamate was also effective in both the CUMS and CSDS models of depression. Moreover, felbamate administration fully restored the decreased hippocampal BDNF signaling pathway in both the CUMS‐stressed and CSDS‐stressed mice. Collectively, felbamate has antidepressant‐like actions in mice involving the hippocampal BDNF system.     

慢性温和不可预知应激抑郁模型大鼠脑组织1H-NMR代谢组学研究

目的 采用高分辨核磁共振¹H谱（¹H-NMR）代谢组学技术研究慢性温和不可预知应激（CUMS）抑郁大鼠脑组织中代谢物及代谢通路的变化，探讨抑郁症的发病机制。方法 12只雄性SD大鼠随机分为模型组和对照组，采用CUMS对模型组大鼠进行为期4周的造模，进行称体质量、旷场实验和糖水偏爱实验验证模型是否成功，造模结束后收集大鼠脑组织。采用两相提取法（甲醇/氯仿/水）对脑组织进行提取，得到水溶性和脂溶性代谢物。应用¹H-NMR技术结合多元统计和代谢通路分析筛选出与抑郁相关的脑内差异代谢物，并构建其代谢通路。结果 行为学数据显示，与对照组比较，模型组大鼠的体质量、糖水偏爱率、旷场的穿格数和直立次数均显著降低（P<0.05），显示了抑郁状态。在大鼠脑组织的¹H-NMR图谱中共指认出35种内源性代谢产物。脑组织中水溶性和脂溶性代谢物主成分分析（PCA）均显示模型组与对照组分开，与行为学结果一致，表明造模成功；OPLS-DA分析找到9个水溶性差异代谢物和6个脂溶性差异代谢物。就水溶性代谢物而言，与对照组比较，模型组中肌酐、谷氨酰胺、牛磺酸和γ-氨基丁酸含量显著增加（P<0.05、0.01、0.001），丙二醇、谷氨酸、亮氨酸、缬氨酸和赖氨酸含量显著降低（P<0.05、0.01、0.001）。就脂溶性代谢物而言，与对照组比较，模型组-（CH₂） n和-N （Me₃）₃含量显著升高（P<0.05、0.001），胆固醇的C18/19甲基、R-CH₃、CH₂OPO₂-、-CH=CH-含量显著降低（P<0.05、0.01、0.001）。与对照组比较，CUMS造模后5条代谢通路发生显著变化：缬氨酸、亮氨酸和异亮氨酸生物合成，牛磺酸和亚硫磺酸代谢，丙氨酸、天冬氨酸和谷氨酸代谢，糖降解和糖异生通路和丙酮酸代谢。结论 运用¹H-NMR代谢组学技术结合多元统计分析和代谢通路分析，阐明抑郁症的发病机制与能量代谢、氨基酸代谢和神经递质合成等相关。     

[6]-Shogaol,a dietary phenolic compound,induces oxidative stress mediated mitochondrial dependant apoptosis through activation of proapoptotic factors in Hep-2 cells

Ginger (Zingiber officinale) is a well-known herb used in ethnomedicine. [6]-shogaol, a phenolic nature is a major constituent of ginger. In this study, we investigated the anticancer activity of [6]-shogaol in Laryngeal cancer (Hep-2) cells. We demonstrated the effects of [6]-shogaol on the cell growth and apoptosis in Hep-2 cells were analyzed by the generation of reactive oxygen species (ROS), the level of mitochondrial membrane potential (ΔYm), DNA damage and apoptotic morphological changes were analyzed by AO/EtBr, AO and Hoechst staining. Further, apoptotic protein expressions were analyzed by western blot analysis. Our results indicated that [6]-shogaol induces apoptosis as evidenced by loss of cell viability, enhanced ROS, lipid peroxidation results in altered mitochondrial membrane potential, increased DNA damage in Hep-2 cells. Further, the prooxidant role of [6]-shogaol inhibit Bcl-2 expression with the simultaneous up-regulation of Bax, Cytochrome c, Caspase-9 and -3 protein expressions were observed in Hep-2 cells. Thus, [6]-shogaol induces apoptosis in Hep-2 cells through inducing oxidative damage and modulate apoptotic marker expressions. Therefore, [6]-shogaol might be used as a therapeutic agent for the treatment of laryngeal cancer.     

Prognostic Impact of Combined Late Gadolinium Enhancement on Cardiovascular Magnetic Resonance and Peak Oxygen Consumption in Ambulatory Patients With Nonischemic Dilated Cardiomyopathy

BackgroundPeak oxygen consumption (peak VO₂) and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) are prognostic in heart failure. We investigated whether LGE-CMR and peak VO₂ combined had additive value in risk stratifying patients with nonischemic dilated cardiomyopathy (DCM).Methods and ResultsFifty-seven DCM patients underwent CMR and cardiopulmonary exercise testing. Cardiac events were cardiac death, hospitalization for decompensated heart failure, or lethal arrhythmia. Twenty-five (44%) were LGE-positive. The median peak VO₂ was 18.5 mL·kg^-1·min^-1. On multivariate analysis, positive LGE (P = .048) and peak VO₂ (P = .003) were independent cardiac event predictors. Cardiac event risk was significantly higher with positive LGE and peak VO₂ < 18.5 mL·kg^-1·min^-1 than with negative LGE and peak VO₂ ≥ 18.5 mL·kg^-1·min^-1 (hazard ratio 12.5; 95% CI 1.57–100; P = .017). In 3 patient groups (group A: no LGE, peak VO₂ ≥ 18.5 mL·kg^-1·min^-1, n = 18; group B: positive LGE or peak VO₂ < 18.5 mL·kg^-1·min^-1, n = 24; group C: positive LGE and peak VO₂ < 18.5 mL·kg^-1·min^-1, n = 15) during follow-up (71 ± 32 months), group C had higher cardiac event rates than the others.ConclusionsCombined assessment of LGE-CMR and peak VO₂ provides additive prognostic information in ambulatory DCM.