番茄红素对脂多糖诱导巨噬细胞炎症反应的作用及其分子机制

 【目的】 探讨番茄红素对脂多糖(LPS)所诱导的RAW264.7巨噬细胞炎症因子生成的影响及其作用的分子机制。【方法】 分别用1、5、10 μmol/L 的番茄红素孵育细胞1 h,再用1 μg/mL LPS 处理细胞不同时间,分别用Griess法和ELISA法检测RAW264.7巨噬细胞培养基中NO及IL-6的含量,用Western-blot检测核因子-κB(NF-κB) p65、磷酸化和非磷酸化I-κBα、丝裂原活化蛋白激酶(MAPKs)的蛋白表达量。【结果】 番茄红素能有效地降低炎性因子NO和IL-6分泌,进一步研究显示番茄红素能够抑制LPS诱导I-κBα磷酸化和降解、NF-κB核转移,阻断ERK1/2和p38 MAPK激活,而对JNK活化没有影响。【结论】 番茄红素能够通过抑制ERK1/2 和p38 MAPK信号通路的激活而抑制巨噬细胞NF-κB依赖的炎症因子NO和IL-6生成,这可能是番茄红素防治一些炎症相关性疾病的作用机制之一。     

番茄红素对高脂血症大鼠血细胞和纤溶活性的影响

目的探讨番茄红素对高脂血症大鼠血细胞及纤溶活性的影响。方法成年雄性SD大鼠40只,根据总胆固醇(TC)水平随机分为5组,每组8只:正常对照组、高脂模型组、氟伐他汀钠10mg/kg bw组、番茄红素11mg/kg bw和44mg/kg bw组。正常对照组饲基础饲料,其余组饲高脂饲料,实验第2、3周氟伐他汀钠和番茄红素灌胃处理。检测TC、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-C)、高密度脂蛋白-胆固醇(HDL-C)、超氧化物歧化酶活力(SOD)和丙二醛水平(MDA)、血细胞参数、血小板α颗粒膜蛋白(GMP-140)、组织型纤溶酶原激活物(tPA)、组织型纤溶酶原激活物抑制剂-1(PAI-1),计算tPA/PAI-1比值和动脉粥样硬化指数(AI);HE染色观察主动脉弓的病理变化。结果高脂饲料喂养1周后大鼠形成高脂血症。与模型组比较,番茄红素组的TC、TG、LDL-C和MDA下降,SOD升高;白细胞计数、红细胞体积、血小板体积、GMP-140和PAI-1下降,红细胞计数和tPA上升;AI显著下降,主动脉弓内膜变薄,泡沫细胞减少。番茄红素44mg/kg bw剂量组作用明显。结论番茄红素可能通过降低血脂和抗氧化而保护高脂血症大鼠的血细胞和促进纤溶活性,减轻主动脉病变程度。     

Modulating Oxidative Stress and Inflammation in Elders: The MOXIE Study

Cardiovascular disease (CVD) is the leading cause of death among women in the United States. Endothelial dysfunction and arterial stiffness increase with advancing age and are early predictors of future CVD outcomes. We designed the Modulating Oxidative Stress and Inflammation in Elders (MOXIE) study to examine the effects of 100% watermelon juice as a “food-first” intervention to reduce CVD risk among African American (AA) and European American (EA) women aged 55–69 years. Vascular dysfunction is more pronounced in AA compared to EA women due in part to lower nitric oxide bioavailability caused by higher oxidative stress. However, bioactive compounds in watermelon may improve vascular function by increasing nitric oxide bioavailability and antioxidant capacity. This trial will use a randomized, placebo-controlled, crossover design to investigate the potential of 100% watermelon juice to positively impact various robust measures of vascular function as well as serum biomarkers of oxidative stress and antioxidant capacity. This nutrition intervention and its unique methodology to examine both clinical and mechanistic outcomes are described in this article.     

A randomized controlled trial of lycopene treatment on soluble receptor for advanced glycation end products in seminal and blood plasma of normospermic men

Citation
Oborna I, Malickova K, Fingerova H, Brezinova J, Horka P, Novotny J, Bryndova H, Filipcikova R, Svobodova M. A Randomized controlled trial of lycopene treatment on soluble receptor for advanced glycation end products in seminal and blood plasma of normospermic men. Am J Reprod Immunol 2011; 66: 179–184 Problem The aim of present study was to investigate the effects of antioxidant lycopene on soluble receptor for advanced glycation end products (sRAGE) levels in blood and seminal plasma in normospermic males. Methods Study included 15 fertile volunteers and 13 normospermic male partners from infertile relationships. The treatment was 12‐week administration of 20 mg of lycopene or placebo followed by crossover and treatment for a further 12 weeks. The ELISA kit Quantikine^® was used to determine sRAGE levels. Results Lycopene administration decreased sRAGE levels in seminal plasma in fertile volunteers (controls) as well as in male partners in the infertile relationships group (P = 0.008 and P = 0.012, respectively). No significant effect of lycopene on sRAGE in blood plasma was found in either group, but seminal plasma sRAGE was significantly suppressed. Conclusion Lycopene decreased sRAGE in seminal, but not in blood plasma. This may be because of selective local uptake of lycopene in the male reproductive tract, namely in prostate. Decreased sRAGE may be caused by lycopene suppression of oxidative stressors and explain in part the putative improvement in fertility reported after lycopene treatment.     

Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis‐promoted hepatocarcinogenesis in rats

Epidemiological and experimental studies provide supportive evidence that lycopene (LY), a major carotenoid from tomatoes and tomato products, may act as a chemopreventive agent against certain types of cancers. We recently showed that high‐fat diet (HFD)‐induced nonalcoholic steatohepatitis (NASH) promoted diethylnitrosamine (DEN)‐initiated hepatocarcinogenesis in a rat model. Using this model, we investigated the efficacy of an equivalent dosage of dietary LY from either a pure compound or a tomato extract (TE) against NASH‐promoted hepatocarcinogenesis. Six groups of rats were injected with DEN and then fed either Lieber‐DeCarli control diet or HFD with or without LY or TE for 6 weeks. Results showed that both LY and TE supplementations significantly decreased the number of altered hepatic foci expressing the placental form of glutathione S‐transferase in the livers of HFD‐fed rats. This was associated with significantly lower proliferating cell nuclear antigen positive hepatocytes and cyclinD1 protein, as well as decreased activation of extracellular signal‐regulated kinase and nuclear NF‐κB. Although both LY and TE supplementations reduced HFD‐induced lipid peroxidation in the livers, we observed significantly decreased cytochrome P450 2E1, inflammatory foci and mRNA expression of proinflammatory cytokines (TNF‐α, IL‐1β and IL‐12) in the HFD+TE fed group but increased nuclear NF‐E2‐related factor‐2 and heme oxygenase‐1 proteins in the HFD+LY fed group, relative to HFD feeding alone. These data indicate that LY and TE can inhibit NASH‐promoted hepatocarcinogenesis mainly as a result of reduced oxidative stress, which could be fulfilled through different mechanisms.     

Roles of Diet,Lifetime Physical Activity and Oxidative DNA Damage in the Occurrence of Prostate Cancer among Men in Klang Valley,Malaysia

Background: There is a paucity of information on risk factors of prostate cancer, especially those relatedto dietary and lifestyle among Asian populations. Objective: This study aimed to determine the relationshipbetween dietary intake (macronutrients, fruits, vegetables and lycopene), lifetime physical activity and oxidativeDNA damage with prostate cancer. Design: A case control study was carried out among 105 subjects (case n=35,control n=70), matched for age and ethnicity. Data on sociodemographic, medical, dietary intake, consumptionof lycopene rich food and lifetime physical activity were obtained through an interview based questionnaire.Anthropometric measurements including weight, height and waist hip circumferences were also carried out onsubjects. A total of 3mL fasting venous blood was drawn to assess lymphocyte oxidative DNA damage using thealkaline comet assay. Results: Cases had a significantly higher intake of fat (27.7±5.5%) as compared to controls(25.1±5.9%) (p < 0.05). Mean intaks of fruits and vegetables (3.11 ± 1.01 servings/d)(p<0.05), fruits (1.23 ± 0.59servings/d) (p<0.05) and vegetables (1.97+0.94 servings/d) were higher in controls than cases (2.53 ± 1.01, 0.91± 0.69, 1.62 ± 0.82 servings/d). A total of 71% of cases did not met the recommendation of a minimum of threeservings of fruits and vegetables daily, as compared to 34% of controls (p<0.05) (Adjusted OR 6.52 (95% CI2.3-17.8)) (p<0.05). Estimated lycopene intake among cases (2,339 + 1,312 mcg/d) were lower than controls (3881± 3120mcg/d) (p< 0.01). Estimated lycopene intake of less than 2,498 mcg/day (50th percentile) increased riskof prostate cancer by double [Adjusted OR 2.5 (95%CI 0.99-6.31)]. Intake of tomatoes, watermelon, guava,pomelo, papaya, mango, oranges, dragon fruit, carrot, tomato sauce and barbeque sauce were higher in controlscompared to cases. Intake of tomato sauce of more than 2.24g/d (25th percentile), papaya more than 22.7g/d(50th percentile) and oranges more than 19.1g/h (50th percentile) reduced prostate cancer risk by 7.4 (AdjustedOR 7.4 (95% CI 1.17-46.77)), 2.7 (Adjusted OR 2.75 (95% CI 1.03-7.39)) and 2.6 times (Adjusted OR = 2.6 (95%CI=1.01-6.67)), respectively (p<0.05 for all parameters). No oxidative damage was observed among subjects.Past history of not engaging with any physical activities at the age of 45 to 54 years old increased risk of prostatecancer by approximately three folds (Adjusted OR 2.9(95% CI = 0.8-10.8)) (p < 0.05). In conclusion, low fatdiet, high intake of fruits, vegetables and lycopene rich foods and being physical active at middle age were foundto be protective. Thus, it is essential for Malaysian men to consume adequate fruits and vegetables, reduce fatintake and engage in physical activity in order to reduce prostate cancer risk.     

Consumer acceptability of low-sugar watermelon sweetened with non-calorie sweetener by a Native American community

Watermelons are a good source of lycopene, a carotenoid that exhibits antioxidant activity and may protect against some cancers. However, intake of watermelon may be restricted for individuals who have diabetes or those who limit carbohydrate intake. A low-sugar watermelon was developed at Lane, Oklahoma using traditional plant breeding techniques. The objective of this study was to determine whether the artificially sweetened low-sugar watermelon was acceptable with Native Americans, a group with a high incidence of diabetes. The red flesh from a low-sugar watermelon and a commercial variety of watermelon was removed and cut into cubes. Low and high levels of artificial sweetener were added to the low-sugar watermelon. Students at a Native American school (Grades 1–12) and adults at a Native American Feeding Center were asked to rate how much they liked or disliked the watermelon using a seven-point hedonic scale. Sugar composition, pH, lycopene and other carotenoids were analyzed from samples using established methods. The pH, lycopene, β-carotene and total carotenoid levels were similar among fruit. Artificially sweetened fruit were rated slightly more acceptable in taste than the commercial control watermelons by both age groups. The low-sugar watermelons were lower in sugar composition but were comparable with conventional melons in all other quality factors and were found acceptable in taste by a broad age group of Native American consumers.     

Long-term follow-up of children with classical phenylketonuria after diet discontinuation: a review.

The age at which children suffering from classical phenylketonuria can safely discontinue their dietary therapy has been constantly disputed over the past decades. Recently, most phenylketonuria centers have begun to recommend a life-long diet, especially for female patients. Male patients are also advised to continue their diet until at least well into adult age. As a result of this new outlook in therapy management, we reviewed the existing literature and summarized all relevant long-term follow-up data of children who discontinued their debts at an early age, focusing on intellectual and neurological performance. The abilities of these children are compared during dietary treatment and again several years after diet discontinuation. Results show clearly that children maintaining their diets into their teens have fewer deficits than do those terminating their diets before 10 years of age. It seems essential to initiate diet early, and to keep blood phenylalanine levels < 600 mumol/L and well controlled to at least age 10 to ensure satisfactory long-term development of the patient. Furthermore, it seems highly justified to maintain a life-long diet which can be liberalized, but not completely discontinued in adulthood.