Lycopene and respiratory health -
All of this emphasizes the importance of understanding the common molecular mechanism s driving these two devastating diseases together and the importance of discovering dietary lycopene that can convincingly prevent or delay the progression of COPD and lung cancer. The significance of cholesterol homeostasis has been recognized in lung disease development 19, Cholesterol plays a critical role in cell morphology and function.
Cholesterol intracellular accumulation results in dysregulated inflammatory response 19 , and cholesterol overload can amplify inflammation in macrophages A role of the reverse cholesterol transport RCT , which mediates the removal of excess cholesterol from peripheral tissue, has been shown in the persistent lung inflammation and emphysema after CS exposure in mice Reports from human studies indicated the adverse effect of CS on plasma lipid profile, including decrease of high-density lipoprotein cholesterol HDL-C 23 , which is a main mediator in RCT Furthermore, animal studies have reported that mice deficient in ATP-binding cassette ABC transporters ABCA1 and ABCG1, key transporters of the RCT, have cholesterol overload with abnormal pulmonary morphology and physiology and proinflammatory phenotype 25, Although the role of lycopene in regulation of cholesterol metabolism has been demonstrated 27, 28 , little is known about the role of lycopene in CS exposure—related cholesterol accumulation and pulmonary pathophysiology, such as COPD and lung cancer.
Liver X Receptor LXRα , a nuclear hormone receptor, regulates expression of many genes involved in RCT, including ABCA1 and ABCG1 transporters 29, 30 , which are highly expressed in macrophages and pneumocytes 31, In addition, expression of ABC transporters can be regulated by peroxisome proliferator- activated receptor PPARα , possibly through the LXRα-dependent pathway Recently, anti-inflammatory properties of lycopene have been demonstrated after acute CS exposure in mice Furthermore, new evidence has shown that an LXR agonist can restore altered RCT and suppress inflammation after CS exposure in mice Choosing appropriate animal models is important for potential translational value of the study results to human.
Exposure of ferrets to the CS with or without NNK has been shown as a useful model for studying inflammation 14 , COPD 35 , and lung carcinogenesis 18, Although mice are widely used in animal models for CS exposure studies, CS-exposed mice do not develop all the characteristics of COPD seen in people, such as chronic bronchitis In contrast, CS-exposed ferrets develop both, emphysema and chronic bronchitis, because their lung structure and submucosal gland distribution are similar to those of humans 35, We have previously shown that ferrets closely mimic NNK or CS-induced lung preneoplastic and neoplastic lesions seen in humans 13, 14, Additionally, ferrets are an excellent nonrodent animal model for studying lycopene intervention due to their similarities to humans in carotenoid absorption, metabolism, and tissue accumulation The animal experimental protocol, including exposure to smoke, was approved by the Institutional Animal Care and Use Committee at the Jean Mayer USDA Human Nutrition Research Center on Aging HNRCA at Tufts University.
Fifty-four adult male ferrets 1. Ferrets were fed a semipurified ferret diet D Research Diets ad libitum with free access to water throughout the study. The ferrets were fed lycopene or placebo starting three weeks prior to the NNK injections as a dietary prevention model and continued until the end of the study.
Body weights were recorded weekly. All ferrets were euthanized by terminal exsanguination under deep isoflurane Isothesia; Butler Schein anesthesia, and tissues were harvested and processed for future analyses.
The procedures for both NNK treatment and CS exposure were as described Briefly, for lung tumorigenesis, ferrets were given intraperitoneal i. Control animals were given an injection of normal saline. were mixed with 0. Ferrets spontaneously eat peanut butter, so there was no need to gavage.
The lower dose 2. The sections were examined under light microscopy by two independent investigators who were blinded to the treatment groups.
Lung histopathology of lesions was evaluated and classified as preneoplastic lesions atypical adenomatous hyperplasia and squamous metaplasia and neoplastic lesions including dysplasia, adenocarcinoma, squamous cell carcinoma, adenocarcinoma and squamous cell carcinomas, and bronchioloalveolar carcinoma as described previously The quantification of emphysema in each histologic section of the lung was determined by the mean linear intercept Lm in micrometers from observed microscopic fields.
The measurement of Lm was performed by using a × μm grid that was randomly positioned over each field in the lung section. The total length of each line of the grid divided by the number of alveolar intercepts yielded the average distance between alveolated surfaces Lm in each field.
For each animal, 20 fields at a magnification of 20× were measured, and the mean of the 20 fields was taken as the Lm for each animal.
Total cholesterol TC concentrations were quantified using a commercial cholesterol kit Cell Biolabs Inc. Lung tissue 10 mg was used to determine TC following the manufacturer's instructions. Liver mg tissue, lung mg tissue, and plasma 1 mL were analyzed by the HPLC method to determine concentrations of all- trans and cis isomers 5- cis , cis , and 9- cis of lycopene as previously described Total RNA was isolated from frozen lung tissue using TriPure Isolation Reagent Roche Applied Science following the manufacturer's instructions.
RNA was checked for purity using the NanoDrop spectrophotometer Nanodrop Complementary DNA cDNA was synthetized by reverse transcription using M-MLV Invitrogen using a thermocycler Bio-Rad PTC , GMI following the manufacturer's instructions.
Quantitative real-time PCR was done using specific primers and FastStart Universal SYBR green Master Roche with the real-time PCR machine Applied Biosystems. The nuclear fraction from whole lung cell lysate was prepared as described The protein concentration of the nuclear fraction was determined by Coomassie Plus protein quantification method Thermo Fisher Scientific.
Membranes were incubated with selected primary antibodies LXRα Abcam and PPARα Abcam overnight at 4°C. The protein bands were visualized by a SuperSignal West Chemi-luminescent Substrate Kit Pierce following the manufacturer's instructions.
The intensities of the specific relative band were quantified by using a densitometer GS Calibrated Imaging Densitometer, Bio-Rad. Protein β-actin was used as loading control Sigma-Aldrich.
SAS 9. GraphPad Prism 7 was used for all other analyses. The incidence of preneoplastic or neoplastic lesions was evaluated using the Fisher exact test. The grading of inflammation was evaluated by the Kruskal—Wallis test, followed by the Dunn multiple comparison tests for comparing groups.
One-way ANOVA followed by the Tukey multiple comparison tests was performed for mean values of the multiple groups. Linear or logistic regressions were used to analyze the correlation between emphysema, chronic bronchitis, preneoplastic lesions, and TC in lungs.
The results are expressed as means ± SEMs. B, Distribution of inflammation grade in groups. D, Distribution of alveolar diameter expressed as mean linear intercept Lm, μm in groups. Statistical significance for emphysema was determined by one-way ANOVA. The grading of inflammation was analyzed by Kruskal—Wallis test.
Lm C, Tumors visible on lung surface arrows. The incidence of preneoplastic and neoplastic lesions was evaluated using Fisher exact test. There was no significant difference in BW among all groups at the end of the study Table 1.
Plasma levels of TG, LDL-C, and VLDL-C were not significantly different between the groups. One-way ANOVA was used to examine the difference between the overall groups. Abbreviations: TG, triglycerides; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; VLDL-C, very-low-density lipoprotein cholesterol.
In the lung tissues, mRNA expression and protein levels of genes related to reverse cholesterol transport were determined by RT-qPCR and immunoblotting, respectively Fig. A, Relative mRNA expression of the RCT biomarkers ABCA1, ABCG1, LXRα , and PPARα in lung tissue lysate.
B, Relative protein levels of nuclear hormone receptors LXRα and PPARα in lungs. Statistical difference was determined by the one-way ANOVA.
Lycopene was detected in the plasma and livers Table 2 , but not in the lungs of ferrets fed lycopene. Animals in the high-dose lycopene group had higher total lycopene concentration than the low-dose lycopene group in plasma and livers, but the difference was not significant.
The high-dose lycopene group had higher plasma and liver accumulation of all -trans isomer compared with the low-dose lycopene group, but only the difference in plasma was significant. We observed a nonsignificant increase in 5- cis and 9- cis in high lycopene group relative to low lycopene group in both, plasma and liver, whereas the increase in cis isomers reached significance in plasma, but not liver.
There was more trans -isomer in plasma than cis -isomer in low-dose and high-dose lycopene groups ratios of trans : cis isomers, ; , respectively. The ratios of trans : cis isomers in liver were and in low-dose and high-dose lycopene groups, respectively Table 2.
Abbreviation: ND, not detected. We demonstrated that ferrets exposed to the combination of NNK and CS resulted in chronic bronchitis and emphysema, accompanied with preneoplastic and neoplastic lesions in the lungs of ferrets, indicating ferrets as an excellent model for studying COPD and lung cancer in preclinical settings.
The observed protective effect was strongly associated with the attenuation of TC accumulation in lungs and plasma. Many studies indicated the importance of cholesterol in lung disease development, including COPD and lung carcinogenesis 19, 20, 22, 25, 39, We observed that ferrets had plasma TC levels comparable with humans, which is in contrast to most other laboratory animals that have lower blood TC levels This suggests that the ferret is an ideal model for studying effect of CS on plasma TC in humans.
Our results are in agreement with previous studies where alterations in RCT led to cholesterol overload, abnormal structure and function in lungs of mice 25, 26, ABCA1 and ABCG1 are the direct target genes of LXRα. PPARα can enhance RCT A secondary goal was to see if dietary factors influence lycopene levels in the blood.
Materials and Methods : A retrospective cohort study of 14, adults who took part in Phase II of the National Health and Nutrition Examination Survey III was carried out This dataset served as the baseline for a year follow-up study, which was correlated with the National Death Index database.
The Cox Proportional Hazards Regression Model was used to calculate the HR for all-cause and cancer-related deaths for individuals with high, moderate, and low serum lycopene levels. Results : The unadjusted hazard ratio HR of deaths associated with low serum lycopene levels 25 percent cutoff was 1.
After controlling for multiple risk factors such as age and gender, the HR for lung cancer fatalities was 1. For low vs. high serum lycopene levels, the adjusted HR for lung cancer death using 3-level categorization and adjusted for fruits and vegetables was 1.
In addition, the adjusted HR for lung cancer death using 3-level categorization and unadjusted for fruits and vegetables was 1. high serum lycopene levels.
Conclusions : The results suggest that high serum lycopene levels may reduce the risk of dying from lung cancer. Furthermore, lycopene may not only reduce the risk of lung cancer development but may also improve survival among lung cancer patients.
More research is needed to understand the physiological mechanisms underlying this association. This open-access article is distributed by the terms and conditions of the Creative Commons Attribution 4.
Alpha-Tocopherol, Beta-Carotene Cancer Prevention. Beta-Carotene and Retinol Efficacy Trial. chronic obstructive pulmonary disease. Surveillance, Epidemiology, and End Results. Google Scholar Crossref. Search ADS. American Cancer Society. Accessed August 3, Google Scholar Google Preview OpenURL Placeholder Text.
World Cancer Research Fund; American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Fruit and vegetable consumption and lung cancer risk: updated information from the European Prospective Investigation into Cancer and Nutrition EPIC.
Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies. Consumption of fruit and vegetables and risk of lung cancer: a case-control study in Galicia, Spain. Vegetable and fruit consumption and lung cancer risk in the Netherlands Cohort Study on diet and cancer.
Google Scholar PubMed. OpenURL Placeholder Text. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study.
Nutrition and lung cancer: lessons from the differing effects of foods and supplements. Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, — Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer.
VITamins And Lifestyle cohort study: study design and characteristics of supplement users. Montvale, NJ: Medical Economics Company; Reliability and validity of self-report of vitamin and mineral supplement use in the Vitamins and Lifestyle Study.
Measurement characteristics of the Women's Health Initiative food frequency questionnaire. Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: a pooled analysis of 8 prospective studies. De Stefani.
A multicenter case-control study of diet and lung cancer among non-smokers. Dietary antioxidants and lung cancer risk: a case-control study in Uruguay. Intake of specific carotenoids and flavonoids and the risk of lung cancer in women in Barcelona, Spain.
Dietary carotenoids, vegetables, and lung cancer risk in women: the Missouri women's health study United States. Intake of specific carotenoids and risk of lung cancer in 2 prospective U.
Diet and alcohol consumption and lung cancer risk in the New York State Cohort United States. Dietary carotenoids, serum β-carotene, and retinol and risk of lung cancer in the Alpha-Tocopherol, Beta-Carotene cohort study. A cohort study of dietary carotenoids and lung cancer risk in women Canada.
Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease.
Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. Beta-carotene and lung cancer: a lesson for future chemoprevention investigations [electronic article]? Serum alpha-tocopherol and subsequent risk of lung cancer among male smokers.
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This Feature Is Available To Subscribers Only Sign In or Create an Account. Education b. Family history of lung cancer d. Adjusted Hazard Ratio d. β-Carotene no. of years a used over 10 years e. β-Carotene year average daily dose e.
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Jelena Heaoth RakicChun Lycopene and respiratory healthXnd Veeramachaneni respiraotry, Dayong Wu Lycopene and respiratory health, Ligi Cranberry health remediesAdn. Oliver ChenLycopene and respiratory health M. AusmanLyclpene Wang; Lycopene Inhibits Heallth Chronic Obstructive Pulmonary Disease and Lung Carcinogenesis by Modulating Reverse Cholesterol Transport in Ferrets. Cancer Prev Res Phila 1 July ; 12 7 : — Chronic obstructive pulmonary disease COPD and lung cancer share the same etiologic factor, cigarette smoking. Higher consumption of dietary lycopene has been associated with lower risks of COPD and lung cancer in smokers. We investigated whether lycopene feeding protects against COPD and lung cancer in ferrets, a nonrodent model that closely mimics cigarette smoke CS -induced chronic bronchitis, emphysema, and lung tumorigenesis in human. Lycopene and respiratory health Afriyie-GyawuGeorgia Southern University, Lycpene Hsu Lycopene and respiratory health of Public Health Despiratory Padmini ShankarGeorgia Southern University Follow Gulzar H. ShahGeorgia Southern University, Jiann-Ping Artichoke main courses College of Public Health Lycopene and respiratory health Alicia Repsiratory. BrownGeorgia Southern University, Jiann-Ping Respiraory College of Public Health Follow Shannon CearleyGeorgia Southern University Follow Akwasi Ampofo-YeboahUniversity for Development Studies Follow Nathaniel AbramsKwame Nkrumah University of Science and Technology Jian ZhangKwame Nkrumah University of Science and Technology. Background : Lycopene is a carotenoid found in some fruits and vegetables that is responsible for the red pigment in tomatoes and tomato products. Objective : The primary objective of this study was to see if there was a link between lycopene levels in the blood and lung cancer mortality.
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