Integration of bioassay and non-target metabolite analysis of tomato reveals that ß-carotene and lycopene activate the adiponectin signaling pathway, including AMPK phosphorylation.

Adiponectin, an adipokine, regulates glucose metabolism and insulin sensitivity through the adiponectin receptor (AdipoR). In this study, we searched for metabolites that activate the adiponectin signaling pathway from tomato (Solanum lycopersicu). Metabolites of mature tomato were separated into 55 fractions by liquid chromatography, and then each fraction was examined using the phosphorylation assay of AMP-protein kinase (AMPK) in C2C12 myotubes and in AdipoR-knockdown cells by small interfering RNA (siRNA). Several fractions showed AMPK phosphorylation in C2C12 myotubes and siRNA-mediated abrogation of the effect. Non-targeted metabolite analysis revealed the presence of 721 diverse metabolites in tomato. By integrating the activity of fractions on AMPK phosphorylation and the 721 metabolites based on their retention times of liquid chromatography, we performed a comprehensive screen for metabolites that possess adiponectin-like activity. As the screening suggested that the active fractions contained four carotenoids, we further analyzed ß-carotene and lycopene, the major carotenoids of food. They induced AMPK phosphorylation via the AdipoR, Ca2+/calmodulin-dependent protein kinase kinase and Ca2+ influx, in addition to activating glucose uptake via AdipoR in C2C12 myotubes. All these events were characteristic adiponectin actions. These results indicated that the food-derived carotenoids, ß-carotene and lycopene, activate the adiponectin signaling pathway, including AMPK phosphorylation.

Effect of Lycopene Intake on the Fasting Blood Glucose Level: A Systematic Review with Meta-Analysis.

Lycopene is a lipophilic unsaturated carotenoid exhibiting a strong singlet oxygen-quenching ability. Herein, we investigated the effect of lycopene intake on the fasting blood glucose (FBG) level by conducting a systematic review and meta-analyses. We searched 15 databases (from the earliest date to June 2022 for PubMed or to August or September 2018 for the other databases) and included human interventional studies that assessed the effects of oral lycopene intake on FBG levels of participants ≥ 18 years of age. Three authors independently selected applicable studies and then assessed the study quality. Data were pooled as standardized mean difference (SMD) and analyzed by the random-effects model. Heterogeneity was assessed by I2 statistics. A meta-analysis including 11 trial arms (n = 750) revealed a tendency towards a significant decrease in FBG level with not-important heterogeneity [SMD = -0.15 (95% CI: -0.31, 0.00), p = 0.05, I2 = 9%]. Subgroup meta-analysis including two studies (n = 152) in type 2 diabetes patients revealed significantly decreased FBG levels with not-important heterogeneity [SMD = -0.37 (95% CI: -0.69, -0.05), p = 0.02, I2 = 0%]. Most studies meeting the eligibility criteria had a moderate risk of bias. The funnel plot for FBG suggested an absence of publication bias. In conclusion, this systematic review and meta-analyses suggested that lycopene intake exerted an FBG-decreasing effect.

Lycopene intake induces colonic regulatory T cells in mice and suppresses food allergy symptoms.

BACKGROUND: Food allergy (FA) is a common disease in children; thus, a high level of safety is required for its prevention and treatment. Colonic regulatory T cells (Tregs) have been suggested to attenuate FA. We investigated the Treg-inducing ability and anti-FA effects of carotenoids, a pigment contained in vegetables and fruits. METHODS: C57BL/6N mice were fed a diet containing 0.01% (w/w) of lycopene, ß-carotene, astaxanthin or lutein for 4 weeks, and the population of colonic Tregs was assessed. Subsequently, to evaluate the Treg-inducing ability of lycopene, splenic naïve CD4+ T cells from BALB/c mice were cultured with anti-CD3/CD28 antibody, TGF-ß and lycopene, and the frequencies of Tregs were examined. The effect of 0.1% (w/w) lycopene containing diet on FA was investigated in OVA-induced FA model BALB/c mice. RESULTS: In screening, only lycopene significantly increased the frequency and number of colonic Tregs. Lycopene also increased Treg differentiation in splenic naïve CD4+ T cells. In FA mice, lycopene feeding significantly increased the number of colonic Tregs and attenuated allergic symptoms. The expression levels of IL-4, IL-9 and IL-13 mRNA in colonic mucosa were also significantly reduced by lycopene. IL-9 is known to induce proliferation of mast cells, and we found that lycopene feeding significantly reduced the number of mast cells in the colonic mucosa of FA mice. CONCLUSION: Our results suggest that lycopene, a carotenoid present in many common foods on the market, may have the potential to induce colonic Tregs and suppress FA symptoms.

Effects of lycopene intake on HDL-cholesterol and triglyceride levels: A systematic review with meta-analysis.

Lycopene is a lipophilic unsaturated carotenoid and has a very strong singlet oxygen-quenching ability. Increased serum or plasma lycopene levels have been reported to be associated with a lower risk of metabolic syndrome. We aimed to investigate the effects of lycopene intake on blood HDL-cholesterol (HCL-c) and triglyceride (TG) levels, which are metabolic syndrome biomarkers, by systematic review and meta-analyses of human interventional trials. We searched 15 databases and included studies that assessed the effects of oral lycopene intake on blood HDL-c and TG levels of participants ≥18 years of age. Three reviewers independently selected applicable studies, then assessed study qualities. Data were pooled as standardized mean difference (SMD) and analyzed by random-effects model. Heterogeneity was assessed by I2 statistics. Meta-analysis including 12 trial arms (n = 781) revealed a significantly increased HDL-c level in the lycopene group compared with that in the control group (SMD = 0.33 [95% CI: 0.12, 0.54], p = 0.002) and moderate heterogeneity (I2  = 45%). Most subgroup meta-analyses (restricted to study design, test food type, intake period, and participants' characteristics) showed similar results for HDL-c level. On the other hand, meta-analysis including 11 studies (n = 854) revealed no significant difference in TG level between the lycopene and control groups. Most studies which met eligibility criteria had moderate risk of bias. Funnel plots for HDL-c and TG suggested an absence of publication bias. In conclusion, this systematic review and meta-analyses suggested that lycopene intake significantly improved blood HDL-c levels but not TG levels.

TOMATOMET: A metabolome database consists of 7118 accurate mass values detected in mature fruits of 25 tomato cultivars.

The total number of low-molecular-weight compounds in the plant kingdom, most of which are secondary metabolites, is hypothesized to be over one million, although only a limited number of plant compounds have been characterized. Untargeted analysis, especially using mass spectrometry (MS), has been useful for understanding the plant metabolome; however, due to the limited availability of authentic compounds for MS-based identification, the identities of most of the ion peaks detected by MS remain unknown. Accurate mass values of peaks obtained by high accuracy mass measurement and, if available, MS/MS fragmentation patterns provide abundant annotation for each peak. Here, we carried out an untargeted analysis of compounds in the mature fruit of 25 tomato cultivars using liquid chromatography-Orbitrap MS for accurate mass measurement, followed by manual curation to construct the metabolome database TOMATOMET (http://metabolites.in/tomato-fruits/). The database contains 7,118 peaks with accurate mass values, in which 1,577 ion peaks are annotated as members of a chemical group. Remarkably, 71% of the mass values are not found in the accurate masses detected previously in Arabidopsis thaliana, Medicago truncatula or Jatropha curcas, indicating significant chemical diversity among plant species that remains to be solved. Interestingly, substantial chemical diversity exists also among tomato cultivars, indicating that chemical profiling from distinct cultivars contributes towards understanding the metabolome, even in a single organ of a species, and can prioritize some desirable metabolic targets for further applications such as breeding.

Matrix-assisted laser desorption/ionization mass spectrometry-guided visualization analysis of intestinal absorption of acylated anthocyanins in Sprague-Dawley rats.

It is unknown whether intestinal absorption of acylated anthocyanins occurs in their intact or metabolized form. In this study, with the aid of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging, intestinal absorption of acylated anthocyanins was visually investigated. Anthocyanin extracts from purple carrots were orally administered to Sprague-Dawley rats. Acylated cyanidins were absorbed into portal and circulating blood systems in their intact form, and aglycon; cyanidin 3-O-(6-O-feruloyl-ß-d-glucopyranosyl)-(1 â†’ 6)-[ß-d-xylopyranosyl-(1 â†’ 2)]-ß-d-galactopyranoside (Cy3XFGG), and showed a high absorption of 39.3 ± 0.1 pmol/mL-plasma at 60 min after administration. MALDI-MS imaging analysis of the rat jejunum membranes showed that an organic anion transporting polypeptide (OATP) transporter was involved in Cy3XFGG transport, while deacylated anthocyanins were incorporated through both the glucose transporter 2 and OATP routes. In conclusion, acylated anthocyanin, Cy3XFGG, can be absorbed in its intact form through intestinal OATP.

Tomato Juice Consumption Could Improve Breast Skin Adverse Effects of Radiotherapy in Breast Cancer Patients.

BACKGROUND/AIM: We investigated the beneficial effects of drinking tomato juice (TJ) rich in antioxidant carotenoids on irradiated skin following radiotherapy (RT) in breast cancer patients. PATIENTS/METHODS: Twenty-three patients agreed to drink TJ (160 g/day for six months) after the completion of RT. Early and late adverse events (AEs) of irradiated skin were evaluated according to the Common Terminology Criteria for AEs and the European Organization for Research and Treatment of Cancer Global Cosmetic Rating System, respectively. RESULTS: With regard to early AEs, acute radiodermatitis of grade 1 was observed in most patients (22/23) at the end of RT. However, the grade of radiodermatitis rapidly changed to 0, 1 month after RT and starting TJ consumption. With regard to late AEs, most patients were in good or excellent dermal condition. CONCLUSION: TJ consumption could help in relieving and recovering from early AEs and decreasing the severity of late AEs of irradiated skin.

Acylated anthocyanins derived from purple carrot (Daucus carota L.) induce elevation of blood flow in rat cremaster arteriole.

Acylated anthocyanins are more stable than monomeric anthocyanins, but little is known about their physiological effects. We evaluated the hemodynamic effects of single intragastric doses of purple carrot (Daucus carota L.) anthocyanin (PCA) and two monomeric anthocyanins, cyanidin 3-O-glycoside (C3G) and delphinidin 3-O-ruthenoside (D3R). PCA, C3G, or D3R was administered orally to rat and blood flow in the cremaster artery was measured for 60 min using a laser Doppler blood flow meter. After measurements, the aorta of the animal was removed and the extent of phosphorylation of aortic epithelial nitric oxide synthase (eNOS) and Akt were determined by western blotting. PCA (10 mg kg-1) or C3G (1 mg kg-1) significantly increased rat cremaster arteriole blood flow and phosphorylation of eNOS and Akt; D3G (1 mg kg-1) only slightly altered cremaster arteriole blood flow and did not affect the phosphorylation of eNOS and Akt in the aorta. These results suggest that hemodynamic alterations depend more on the chemical structure of anthocyanins, particularly the aglycon, than on the glycoside. In addition, increase of blood flow by a single oral dose of PCA was practically reduced with treatment of carvedilol (CR), a non-specific adrenaline blocker. Blood concentrations of cyanidin or its glycoside 15, 30, or 60 min after the administration of 10 mg kg-1 PCA were below the limit of detection. These hemodynamic changes may have been associated with an indirect adrenergic action induced following a single dose of PCA.

Apo-12'-lycopenal, a Lycopene Metabolite, Promotes Adipocyte Differentiation via Peroxisome Proliferator-Activated Receptor γ Activation.

Apo-lycopenals, lycopene metabolites produced by an initial cleavage by ß,ß-carotene-9',10'-oxygenase, exhibit diverse biologically active effects. In this study, we investigated the effect of apo-lycopenals on the activation of nuclear receptors involved in glucose and lipid metabolism. Only apo-12'-lycopenal exhibited selective and dose-dependent transactivation activity for peroxisome proliferator-activated receptor γ (PPARγ), whereas neither apo-6'- nor apo-8'-lycopenals displayed this activity ((7.83 ± 0.66)-, (1.32 ± 0.10)-, and (1.31 ± 0.37)-fold higher activity relative to control, respectively). Additionally, apo-12'-lycopenal promoted adipocyte differentiation of 3T3-L1 cells and subsequently increased the mRNA levels of PPARγ (a (2.36 ± 0.07)-fold increase relative to control; p < 0.01) and its target genes, as well as enhanced adiponectin secretion (a (3.25 ± 0.27)-fold increase relative to control; p < 0.01) and insulin-stimulated glucose uptake (1486 ± 85 pmol/well; p < 0.001) in 3T3-L1 cells. Our results indicated that apo-12'-lycopenal promoted adipocyte differentiation by direct binding and activation of PPARγ.

Dietary Tomato Powder Inhibits High-Fat Diet-Promoted Hepatocellular Carcinoma with Alteration of Gut Microbiota in Mice Lacking Carotenoid Cleavage Enzymes.

Both incidence and death rate due to liver cancer have increased in the United States. Higher consumption of lycopene-rich tomato and tomato products is associated with a decreased risk of cancers. ß-Carotene-15, 15'-oxygenase (BCO1), and ß-carotene-9', 10'-oxygenase (BCO2) cleave lycopene to produce bioactive apo-lycopenoids. Although BCO1/BCO2 polymorphisms affect human and animal lycopene levels, whether dietary tomato consumption can inhibit high-fat diet (HFD)-promoted hepatocellular carcinoma (HCC) development and affect gut microbiota in the absence of BCO1/BCO2 is unclear. BCO1/BCO2 double knockout mice were initiated with a hepatic carcinogen (diethylnitrosamine) at 2 weeks of age. At 6 weeks of age, the mice were randomly assigned to an HFD (60% of energy as fat) with or without tomato powder (TP) feeding for 24 weeks. Results showed that TP feeding significantly decreased HCC development (67%, 83%, and 95% reduction in incidence, multiplicity, and tumor volume, respectively, P < 0.05). Protective effects of TP feeding were associated with (1) decreased hepatic inflammatory foci development and mRNA expression of proinflammatory biomarkers (IL1ß, IL6, IL12α, monocyte chemoattractant protein-1, and inducible NO synthase); (2) increased mRNA expression of deacetylase sirtuin 1 and nicotinamide phosphoribosyltransferase involving NAD+ production; and (3) increased hepatic circadian clock genes (circadian locomotor output cycles kaput, period 2, and cryptochrome-2, Wee1). Furthermore, TP feeding increased gut microbial richness and diversity, and significantly decreased the relative abundance of the genus Clostridium and Mucispirillum, respectively. The present study demonstrates that dietary tomato feeding independent of carotenoid cleavage enzymes prevents HFD-induced inflammation with potential modulating gut microbiota and inhibits HFD-promoted HCC development.

Lactobacillus brevis KB290 With Vitamin A Ameliorates Murine Intestinal Inflammation Associated With the Increase of CD11c+ Macrophage/CD103- Dendritic Cell Ratio.

Background: The ratio of colonic anti-inflammatory CD11c+ macrophages (MPs) to inflammatory CD103- dendritic cells (DCs) plays pivotal roles in intestinal inflammation. Little is known about how the ratio is regulated by lactic acid bacteria (LAB) and bifidobacteria (Bif). We investigated the contribution of LAB/Bif to this ratio. Methods: We established an in vitro experimental system using human myeloblastic KG-1 cells, which differentiate into CD11c+ MP-like (CD11c+ MPL) and CD103- DC-like (CD103- DCL) cells, and explored effective LAB/Bif strains. The selected strain's effect on the colonic CD11c+ MP/CD103- DC ratio and intestinal inflammation was examined in mice, and the strain's underlying mechanisms were investigated in vitro. Results: We screened 19 strains of LAB/Bif, and found that Lactobacillus brevis KB290 (KB290) increased the CD11c+ MPL/CD103- DCL cell ratio only in the presence of a vitamin A (VA) metabolite, retinoic acid (RA). Supplementation of KB290 with VA increased the CD11c+ MP/CD103- DC ratio in healthy mouse and prevented the disruption of the ratio during colitis. Supplementation of KB290 with pro-VA (ß-carotene) also increased the ratio in healthy mouse and ameliorated the development of colitis. The ratio was increased by reduction of CD103- DCs (or CD103- DCL cells). Our in vitro data suggested that KB290 induced cell death in CD103- DCL cells in the presence of RA signaling. Conclusions: Supplementation of KB290 with VA increases the colonic CD11c+ MP/CD103- DC ratio associated with the amelioration of murine colitis, suggesting a possible way to control intestinal inflammation by LAB.

Wide-range screening of anti-inflammatory compounds in tomato using LC-MS and elucidating the mechanism of their functions.

Obesity-induced chronic inflammation is a key factor in type 2 diabetes. A vicious cycle involving pro-inflammatory mediators between adipocytes and macrophages is a common cause of chronic inflammation in the adipose tissue. Tomato is one of the most popular vegetables and is associated with a reduced risk of diabetes. However, the molecular mechanism underlying the effect of tomato on diabetes is unclear. In this study, we focused on anti-inflammatory compounds in tomato. We found that the extract of tomato reduced plasma glucose and inflammatory markers in mice. We screened anti-inflammatory fractions in tomato using lipopolysaccharide-stimulated RAW264.7 macrophages, and active compounds were estimated by liquid chromatography-mass spectrometry over a wide range. Surprisingly, a large number of compounds including oxylipin and coumarin derivatives were estimated as anti-inflammatory compounds. Especially, 9-oxo-octadecadienoic acid and daphnetin suppressed pro-inflammatory cytokines in RAW264.7 macrophages inhibiting mitogen-activated protein kinase phosphorylation and inhibitor of kappa B α protein degradation. These findings suggest that tomato containing diverse anti-inflammatory compounds ameliorates chronic inflammation in obese adipose tissue.

Tomato Powder Inhibits Hepatic Steatosis and Inflammation Potentially Through Restoring SIRT1 Activity and Adiponectin Function Independent of Carotenoid Cleavage Enzymes in Mice.

SCOPE: Beta-carotene-15,15'-oxygenase (BCO1) and beta-carotene-9',10'-oxygenase (BCO2) metabolize lycopene to biologically active metabolites, which can ameliorate nonalcoholic fatty liver disease (NAFLD). We investigate the effects of tomato powder (TP containing substantial lycopene (2.3 mg/g)) on NAFLD development and gut microbiome in the absence of both BCO1 and BCO2 in mice. METHOD AND RESULTS: BCO1-/- /BCO2-/- double knockout mice were fed a high fat diet (HFD) alone (n = 9) or with TP feeding (n = 9) for 24 weeks. TP feeding significantly reduced pathological severity of steatosis and hepatic triglyceride levels in BCO1-/- /BCO2-/- mice (p < 0.04 vs HFD alone). This was associated with increased SIRT1 activity, nicotinamide phosphoribosyltransferase expression and AMP-activated protein kinase phosphorylation, and subsequently decreased lipogenesis, hepatic fatty acid uptake, and increasing fatty acid ß-oxidation (p < 0.05). TP feeding significantly decreased mRNA expression of proinflammatory genes (tnf-α, il-1ß, and il-6) in both liver and mesenteric adipose tissue, which were associated with increased plasma adiponectin and hepatic adiponectin receptor-2. Multiplexed 16S rRNA gene sequencing was performed using DNA extracted from cecum fecal samples. TP feeding increased microbial richness and decreased relative abundance of the genus Clostridium. CONCLUSION: Dietary TP can inhibit NAFLD independent of carotenoid cleavage enzymes, potentially through increasing SIRT1 activity and adiponectin production and decreasing Clostridium abundance.

Possible benefits of tomato juice consumption: a pilot study on irradiated human lymphocytes from healthy donors.

BACKGROUND: Reactive oxygen species (ROS) mediate much of the DNA damage caused by ionizing radiation. Among carotenoids, lycopene and ß-carotene, present in tomato juice, are known to be strong radical scavengers. The aim of the study was to investigate the effect of tomato juice intake on the levels of DNA damage and oxidative stress in human whole blood induced by in vitro exposure to X-rays. METHODS: Ten healthy adults were asked to drink 190 g of tomato juice, containing 17 mg lycopene and 0.25 mg ß-carotene, per day for 3 weeks and then refrain from drinking it for 3 weeks. Peripheral whole blood samples were collected before and after the intake period of tomato juice and after the washout period. The blood samples were exposed in vitro to X-ray doses of 0, 0.1, 0.5, and 2 Gy. Cytogenetic damage was measured using the cytokinesis-block micronucleus (CBMN) assay and the dicentrics (DIC) assay. The level of oxidative stress was determined using serum 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxo-dG) and plasma reactive oxygen metabolite-derived compounds (d-ROMs). The concentration of carotenoids in plasma was measured at the three time points. RESULTS: The levels of 8-oxo-dG tended to decrease during the intake period and increase during the washout period. A non-significant inverse correlation was noted between the plasma concentration of lycopene plus ß-carotene and the level of 8-oxo-dG (P = 0.064). The radiation-induced MN and DIC frequencies increased in a dose-dependent manner, and when compared at the same dose, the MN and DIC frequencies decreased during the intake period compared with those at baseline and then increased during the washout period. The results suggest that continuous tomato juice consumption non-significantly decreases extracellular 8-oxo-dG, d-ROMs, and MN. Tomato juice intake had minimal or no effect on radiation-induced 8-oxo-dG and d-ROMs. For most radiation doses, continuously tomato juice intake lowered the levels of MN and DIC. CONCLUSION: Tomato juice consumption may suppress human lymphocyte DNA damage caused by radiation, but further examination is required. TRIAL REGISTRATION: 2014-001 and 2014-R06.

Effect of combined consumption of Lactobacillus brevis KB290 and ß-carotene on minor diarrhoea-predominant irritable bowel syndrome-like symptoms in healthy subjects: a randomised, double-blind, placebo-controlled, parallel-group trial.

People with non-pathological diarrhoea-predominant irritable bowel syndrome (IBS-D)-like symptoms are present at a significant level even in healthy populations, but established prophylaxis is lacking. Previously, we have found that co-administration of Lactobacillus brevis KB290 (KB290) and ß-carotene (ßC) attenuated murine colitis (potential cause of IBS-D-like symptoms) significantly. Here, we investigated the effect of KB290 and ßC on minor IBS-D-like symptoms in healthy volunteers. After a 4-week run-in period, subjects received a KB290 + ßC or placebo capsule for 12 weeks, followed by a 4-week washout period. The KB290 + ßC group showed a significant improvement in intensity of abdominal pain and stool frequency compared with the placebo group. The KB290 + ßC group showed a significantly higher serum concentration of anti-inflammatory cytokine, interleukin-10, compared with the placebo group. In conclusion, we demonstrated that consumption of KB290 + ßC improves minor IBS-D-like symptoms and inflammatory status in healthy volunteers. (UMIN000018002).

The effects of tomato juice on male infertility.

BACKGROUND AND OBJECTIVES: This study aimed to investigate the effects of tomato juice consumption on seminal plasma lycopene levels and sperm parameters in infertile men. METHODS AND STUDY DESIGN: Subjects were male infertility patients with poor sperm concentration (<20×10 6/mL) and/or motility (<50%). Following a fourweek observation period, subjects were randomly assigned among three groups: a tomato juice group, an antioxidant group, and a control group. The subjects in the tomato juice group and the antioxidant group daily consumed one can of tomato juice (containing 30 mg of lycopene) or one antioxidant capsule (containing vitamin C 600 mg, vitamin E 200 mg, and glutathione 300 mg), respectively, for 12 weeks (feeding period). Seminal plasma lycopene levels and sperm parameters were measured every 6 weeks during the feeding period. RESULTS: Forty-four patients completed the study (control group: 12, antioxidant group: 15, tomato juice group: 17). In the tomato juice group, plasma lycopene level was significantly increased at the 12th week of the feeding period. Moreover, a decrease in seminal plasma white blood cells and an increase in sperm motility in the tomato juice group were statistically significant at the 12th and 6th weeks, respectively, compared to the control group. In the antioxidant capsule group, no significant improvement was observed in semen parameters. CONCLUSIONS: In conclusion, regular consumption of tomato juice seems to improve sperm motility in infertile patients. This is the first report to show that commercially available food, such as tomato juice, might be beneficial for male infertility.

Development of a Singlet Oxygen Absorption Capacity (SOAC) Assay Method. Measurements of the SOAC Values for Carotenoids and α-Tocopherol in an Aqueous Triton X-100 Micellar Solution.

Recently, a new assay method for the quantification of the singlet oxygen absorption capacity (SOAC) of antioxidants (AOs) and food extracts in homogeneous organic solvents was proposed. In this study, second-order rate constants (kQ) for the reaction of singlet oxygen (1O2) with eight different carotenoids (Cars) and α-tocopherol (α-Toc) were measured in an aqueous Triton X-100 (5.0 wt %) micellar solution (pH 7.4, 35 °C), which was used as a simple model of biomembranes. The kQ and relative SOAC values were measured using ultraviolet-visible (UV-vis) spectroscopy. The UV-vis absorption spectra of Cars and α-Toc were measured in both a micellar solution and chloroform, to investigate the effect of solvent on the kQ and SOAC values. Furthermore, decay rates (kd) of 1O2 were measured in 0.0, 1.0, 3.0, and 5.0 wt % micellar solutions (pH 7.4), using time-resolved near-infrared fluorescence spectroscopy, to determine the absolute kQ values of the AOs. The results obtained demonstrate that the kQ values of AOs in homogeneous and heterogeneous solutions vary notably depending on (i) the polarity [dielectric constant (ε)] of the reaction field between AOs and 1O2, (ii) the local concentration of AOs, and (iii) the mobility of AOs in solution. In addition, the kQ and relative SOAC values obtained for the Cars in a heterogeneous micellar solution differ remarkably from those in homogeneous organic solvents. Measurements of kQ and SOAC values in a micellar solution may be useful for evaluating the 1O2 quenching activity of AOs in biological systems.

Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation.

Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8-10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF-κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK-induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF-κB and CYP2E1 in the liver and attenuated the NNK-induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen-associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen-induced pulmonary and hepatic injury.

Development of Singlet Oxygen Absorption Capacity (SOAC) Assay Method Using a Microplate Reader.

Recently, a new assay method that can quantify the singlet oxygen absorption capacity (SOAC) of natural antioxidants and food extracts was developed. The SOAC values were measured in ethanol-chloroform-D2O (50 + 50 + 1, v/v/v) solution at 35°C using a UV-Vis spectrophotometer equipped with a six-channel cell positioner and an electron-temperature control unit. In the present study, measurement of the SOAC values was performed for eight representative carotenoids and three vegetable extracts (tomato, carrot, and red paprika) using a versatile instrument, the microplate reader. A 24-well glass microplate was used for measurements because a plastic microplate, commonly used in the laboratory, dissolves in the ethanol-chloroform-D2O solution. The SOAC values of eight carotenoids and three vegetable extracts measured using a microplate reader were in good agreement with the corresponding values measured using a UV-Vis spectrophotometer, suggesting that the microplate reader is an applicable instrument for the measurement of reliable SOAC values for general antioxidants and food extracts in solution.