A Dose-Response Study on the Effects of Purified Lycopene Supplementation on Biomarkers of Oxidative Stress

Objective: While tomato product supplementation, containing antioxidant carotenoids, including lycopene, decreases oxidative stress, the role of purified lycopene as an antioxidant remains unclear. Thus, we tested the effects of different doses of purified lycopene supplementation on biomarkers of oxidative stress in healthy volunteers.

Methods: This was a double-blind, randomized, placebo-controlled trial, examining the effects of 8-week supplementation of purified lycopene, on plasma lycopene levels, biomarkers of lipid peroxidation {LDL oxidizability, malondialdehyde & hydroxynonenals (MDA & HNE), urinary F₂-isoprostanes}, and markers of DNA damage in urine and lymphocytes. Healthy adults (n = 77, age ≥ 40 years), consumed a lycopene-restricted diet for 2 weeks, and were then randomized to receive 0, 6.5, 15, or 30 mg lycopene/ day for 8 weeks, while on the lycopene-restricted diet. Blood and urine samples were collected at the beginning and end of Week 2 of lycopene-restricted diet, and at end of Week 10 of the study.

Results: Independent of the dose, plasma lycopene levels significantly increased in all lycopene supplemented groups versus placebo (p < 0.05). ANOVA revealed a significant decrease in DNA damage by the comet assay (p = 0.007), and a significant decrease in urinary 8-hydroxy deoxoguanosine (8-OHdG) at 8 weeks versus baseline (p = 0.0002), with 30 mg lycopene/day. No significant inter- or intra-group differences were noted for glucose, lipid profile, or other biomarkers of lipid peroxidation at any dose/time point.

Conclusions: Thus, purified lycopene was bioavailable and was shown to decrease DNA oxidative damage and urinary 8-OHdG at the high dose.     

Lycopene Supplement and Blood Pressure: An Updated Meta-Analysis of Intervention Trials

Epidemiological studies suggested that lycopene supplement could decrease blood pressure, but the results were conflicting. We conducted an updated meta-analysis by screening PubMed databases, and calculated the combined effect size using a random effect model. In addition, subgroup analysis stratified by baseline blood pressure, lycopene dosage, duration, study location and the funding support of the paper was also conducted. Six studies met our inclusion criteria, and the pooled analysis demonstrated a significant reduction of systolic blood pressure (SBP) (mean SBP = −4.953 [−8.820, −1.086], p = 0.012) with obvious heterogeneity (p = 0.034, I² = 58.5%). Subgroup analysis results showed that higher dosage of lycopene supplement (>12 mg/day) could lower SBP more significantly, especially for participants with baseline SBP >120 mmHg, or Asians, while lycopene intervention had no statistical effect on diastolic blood pressure (DBP) (mean DBP = −3.809 [−8.177, 0.560], p = 0.087), and obvious heterogeneity was also observed (p = 0.074, I² = 53.1%). Our present study suggests that lycopene supplement >12 mg/day might effectively decrease SBP, particularly among Asians or population with higher baseline SBP.     

大豆异黄酮对去卵巢大鼠学习记忆和海马谷氨酸细胞及NR2B受体的影响

目的：通过建立H₂O₂诱导心肌细胞氧化应激损伤模型,观察番茄红素（lycopene）对心肌细胞的保护作用。方法：将原代培养的乳鼠心肌细胞随机分为正常组、模型组（H₂O₂）、番茄红素低剂量组（2.5 μmol·L^-1）、番茄红素中剂量组（5 μmol·L^-1）、番茄红素高剂量组（10 μmol·L^-1）。番茄红素与心肌细胞孵育4 h后,再加入H₂O₂,24 h后MTT法测定细胞存活率,比色法测定细胞培养上清液中乳酸脱氢酶（LDH）、肌酸激酶（CK）的含量和细胞超氧化物歧化酶（SOD）、过氧化氢酶（CAT）及丙二醛（MDA）含量,荧光电子显微镜下观察细胞核的形态变化,采用Western blot方法检测细胞凋亡相关蛋白半胱氨酸天冬氨酸蛋白酶-3（Caspase-3）的变化。结果：与正常组比较,模型组心肌细胞存活率降低,心肌细胞LDH和CK释放量增加,SOD,CAT活性降低,MDA含量增加（P<0.01）,呈现出凋亡细胞的特征,Caspase-3的表达增高（P<0.01）。番茄红素高剂量组与模型组比较,心肌细胞的存活率增加（86.36±2.54）%,（54.15±10.97）%,P<0.01,H₂O₂所致乳鼠心肌细胞LDH释放量降低（319.53±23.48）,（495.27±31.57）U·L^-1,P<0.01,CK释放量降低（279.29±32.91）,（397.01±29.36）U·L^-1,P<0.01,SOD活性增高（47.94±2.64）,（37.19±5.78）U·mg^-1,P<0.01,CAT活性增高（34.95±4.67）,（16.35±4.84）U·mg^-1,P<0.01,MDA含量降低（14.27±2.43）,（20.11±2.09）μmol·g^-1,P<0.01,细胞核形态改善,Caspase-3的表达降低（1.40±0.20）,（1.94±0.22）,P<0.05。结论：番茄红素对H₂O₂所致乳鼠心肌细胞氧化应激损伤有明显保护作用。     

Neuroprotective Effect of Lycopene Against PTZ‐induced Kindling Seizures in Mice: Possible Behavioural,Biochemical and Mitochondrial Dysfunction

Oxidative stress and mitochondrial dysfunction are the major contributing factors in the pathophysiology of various neurological disorders. Recently, antioxidant therapies aimed at reducing oxidative stress gained a considerable attention in epilepsy treatment. Lycopene, a carotenoid antioxidant, has received scientific interest in recent years. So, the present study has been designed to evaluate the neuroprotective effect of lycopene against the pentylenetetrazol (PTZ)‐induced kindling epilepsy. Laca mice received lycopene (2.5, 5 and 10 mg/kg) and sodium valproate for a period of 29 days and PTZ (40 mg/kg i.p (Intraperitoneal)) injection on alternative days. Various behavioural (kindling score), biochemical parameters (lipid peroxidation, superoxide dismutase, reduced glutathione, catalase and nitrite) and mitochondrial enzyme complex activities (I, II and IV) were assessed in the brain. Results depicted that repeated administration of a sub‐convulsive dose of PTZ (40 mg/kg) significantly increased kindling score, oxidative damage and impaired mitochondrial enzyme complex activities (I, II and IV) as compared with naive animals. Lycopene (5 and 10 mg/kg) and sodium valproate (100 mg/kg) treatment for a duration of 29 days significantly attenuated kindling score, reversed oxidative damage and restored mitochondrial enzyme complex activities (I, II and IV) as compared with control. Thus, present study demonstrates the neuroprotective potential of lycopene in PTZ‐induced kindling in mice. Copyright © 2015 John Wiley & Sons, Ltd.     

Simultaneous measurement of serum retinol,tocopherols, carotenes,and carotenoids by high performance liquid chromatography

An isocratic, high-performance liquid chromatography method is presented for the simultaneous analysis of retinol, tocopherols, carotenes, and other carotenoids. The method employs detection at two wavelengths (292 and 450 nm) and three internal standards, which are: retinyl acetate, alpha-tocopheryl acetate, and retinyl palmitate. The use of the internal standards is important for accurate quantitation, especially to correct for recovery of beta-carotene. The long-term (n = 81, over three months) precision of the method ranged from a coefficient of variation of 8.2% for retinol to 16% for lycopene. This assay system provides accurate, precise, and rapid analysis and is suitable for longitudinal and cross-sectional large-scale epidemiological studies of these vitamins.     

Synthetic and tomato-based lycopene have identical bioavailability in humans

Summary. Background: Bioavailability studies with lycopene have focused on natural sources. A synthetic source has recently become available. Aim of the study: To determine the relative bioavailabilities of synthetic and tomato-based lycopene in free living volunteers in a single-blind, randomized, placebo-controlled, parallel trial. Methods: Three groups (n=12/group) of healthy, normolipemic male and female subjects with a mean baseline serum lycopene concentration of 0.36 µmol/L took a dose of 15 mg/day total lycopene for 28 days from either Lycovit 10% (beadlets, BASF, Germany) or Lyc-O-Mato (beads, LycoRed Natural Products, Israel) or a placebo (without lycopene) together with the main meal. The increase in serum lycopene from baseline was used as the parameter of bioavailability. Results: Synthetic and tomato-lycopene resulted in significant increases above baseline of serum total lycopene by 0.58 and 0.57 µmol/L, trans-lycopene by 0.34 and 0.41 µmol/L, and total-cis-lycopene by 0.24 and 0.16 µmol/L, whereas no significant changes were found in the placebo treatment. The mean serum total lycopene response to synthetic and natural lycopene was not significantly different. Neither lycopene source affected the other serum carotenoids, viz. -carotene, -carotene, -cryptoxanthin, zeaxanthin and lutein. Conclusion: We conclude that synthetic and natural lycopene are equivalent sources of lycopene and that there is no interaction with other circulating carotenoids.     

番茄红素对高脂血症患者的抗氧化作用

目的研究番茄红素对高脂血症患者的抗氧化作用。方法34例高脂血症患者(甘油三酯>1.88mmol/L)按血脂水平随机分为研究组和对照组,每组17例。研究组患者每日服用番茄红素18mg,服药30天,对照组服用除不含番茄红素外其余成分均与研究组药物成分相同的软胶囊。分别于服药前和停药后测定两组患者的血清超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-Px)活力和丙二醛(MDA)含量。结果服药前研究组与对照组的SOD、GSH-Px活性和MDA含量差异均无显著性。服药后研究组的GSH-Px活性显著高于对照组(P<0.05)。结论番茄红素对高脂血症患者具有抗氧化作用。     

Effect of Carotenoids on Paraoxonase-1 Activity and Gene Expression

Paraoxonase 1 (PON1) is an antioxidant enzyme attached to HDL with an anti-atherogenic potential. It protects LDL and HDL from lipid peroxidation. The enzyme is sensitive to various modulating factors, such as genetic polymorphisms as well as pharmacological, dietary (including carotenoids), and lifestyle interventions. Carotenoids are nutritional pigments with antioxidant activity. The aim of this review was to gather evidence on their effect on the modulation of PON1 activity and gene expression. Carotenoids administered as naturally occurring nutritional mixtures may present a synergistic beneficial effect on PON1 status. The effect of carotenoids on the enzyme depends on age, ethnicity, gender, diet, and PON1 genetic variation. Carotenoids, especially astaxanthin, β-carotene, and lycopene, increase PON1 activity. This effect may be explained by their ability to quench singlet oxygen and scavenge free radicals. β-carotene and lycopene were additionally shown to upregulate PON1 gene expression. The putative mechanisms of such regulation involve PON1 CpG-rich region methylation, Ca(2+)/calmodulin-dependent kinase II (CaMKKII) pathway induction, and upregulation via steroid regulatory element-binding protein-2 (SREBP-2). More detailed and extensive research on the mechanisms of PON1 modulation by carotenoids may lead to the development of new targeted therapies for cardiovascular diseases.