PMID: 

Cancer Cell Int. 2019 ;19:68. Epub 2019 Mar 21. PMID: 30948928

Abstract Title: 

Lycopene improves the efficiency of anti-PD-1 therapy via activating IFN signaling of lung cancer cells.

Abstract: 

Background: Monoclonal antibodies targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) have been developed to treat cancers including lung cancer. In this study, we aimed to investigate whether lycopene could promote the effect of anti-PD-1 treatment on lung cancer.Methods: Tumor formation assay was conducted. Immune reactions were assessed by detecting several cytokine levels using enzyme-like immunosorbent assay. T cell activity was analyzed using cytometry. The mechanism of lycopene action was investigated using Western blot, quantitative real-time polymerase chain reaction and bisulfite sequencing analysis.Results: After the mice injected with Lewis lung carcinoma (LLC) cells were sacrificed, we found that combined lycopene and anti-PD-1 reduced the tumor volume and weight compared to control treatment. Cell apoptosis in the tumor tissues was significantly enhanced in mice with combined lycopene and anti-PD-1 treatment in comparison with those of either lycopene or anti-PD-1 alone. Furthermore, lycopene could assist anti-PD-1 to elevate the levels of interleukin (IL)-1 and interferon (IFN)γ while reduce the levels of IL-4 and IL-10 in the spleen of mice injected with LLC cells. Lycopene treatment increased the CD4+/CD8+ ratio in the spleen and promoted IFNγ-expressing CD8+ T cells in tumor tissues. Upon IFNγ stimulation, lycopene diminished PD-L1 expression via activating JAK andrepressing phosphorylation of AKT.Conclusion: Our results have demonstrated that lycopene could be used as a potential adjuvant drug to synergistically improve the efficiency of anti-PD-1 therapy.

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PMID: 

Environ Toxicol Pharmacol. 2019 Jul ;69:44-50. Epub 2019 Mar 18. PMID: 30953933

Abstract Title: 

Lycopene and resveratrol ameliorate zinc oxide nanoparticles-induced oxidative stress in Nile tilapia, Oreochromis niloticus.

Abstract: 

Industrial products contained nano-zinc oxide (ZnONP) can gain access to the aquaculture environment causing hazardous effects on the living biota. Therefore, this work was planned to examine the ameliorative effects of dietary supplementation of lycopene (LYC) and/or resveratrol (RES) against ZnONP toxicity in Nile tilapia. Five groups with 20 fish each were used; Control, received tap water only; ZnONP group, was intoxicated with ZnONP (50 mg/L); ZnONP-LYC group, was exposed to ZnONP and LYC (500 mg/ kg of the diet); ZnONP-RES group, was exposed to ZnONP and RES (50 mg/kg of the diet); ZnONP-LYC-RES group, was exposed to ZnONP and a combination of LYC and RES. The experiment was continued for 30 days. Fish blood and tissues were then assembled for determination of liver and kidney function and oxidative stress status in liver, kidney, and gills tissue. Results revealed a considerable elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), cholesterol, urea, and creatininewith a noticeable lowering of total proteins and albumin serum levels in response to ZnONP intoxication. In addition, there were significant increase in malondialdehyde (MDA) and reduction in the reduced-glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities. However,treatment with LYC and/or RES ameliorated the ZnONP-inflicted oxidative stress which possibly attributed to their beneficial antioxidant activities.

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PMID: 

Mol Biol Rep. 2019 Jun ;46(3):3387-3397. Epub 2019 Apr 20. PMID: 31006097

Abstract Title: 

Lycopene protects against t-BHP-induced neuronal oxidative damage and apoptosis via activation of the PI3K/Akt pathway.

Abstract: 

Oxidative stress is a key factor of and closely implicated in the pathogenesis of Alzheimer's disease (AD). We herein used tert-butyl hydroperoxide (t-BHP) to induce oxidative stress and mimic oxidative neurotoxicity in vitro. Lycopene is a natural antioxidant that has a strong ability to eliminate free radicals and shows effective protection in some neurodegenerative disease models. However, the effect of lycopene on t-BHP-induced neuronal damage in primary mouse neurons is unknown. This study aimed to investigate the effects of lycopene on t-BHP-induced neuronal damage and the related mechanisms. We found that lycopene pretreatment effectively enhanced the cell viability, improved the neuron morphology, increased the GSH/GSSG level, restored the mitochondrial membrane potential (ΔΨm) and decreased reactive oxygen species generation. Furthermore, lycopene reduced the ratios of Bax:Bcl-2 and cleaved caspase-3:caspase-3 and the level of cytochrome C, increased the levels of synaptophysin (SYP) and postsynaptic density 95 (PSD95) and activated the PI3K/Akt pathway. In conclusion, lycopene attenuated oxidative stress and reduced t-BHP-induced cell apoptosis, and the mechanism is likely related to activation of the PI3K/Akt pathway. Therefore, lycopene is a potential agent for preventing oxidative stress-mediated AD.

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PMID: 

Eur Rev Med Pharmacol Sci. 2019 Apr ;23(7):3096-3104. PMID: 31002159

Abstract Title: 

Lycopene protects myocardial ischemia injury through anti-apoptosis and anti-oxidative stress.

Abstract: 

OBJECTIVE: The aim of this research was to explore the protective effect of lycopene (Lyc) on myocardial ischemia injury through anti-apoptosis and anti-oxidative stress.MATERIALS AND METHODS: 75 rats were divided into 5 groups: sham operation group (control group), model group, low-dose group (Lyc+2 mg/kg), medium-dose group (Lyc+4 mg/kg) and high-dose group (Lyc+6 mg/kg). The rat model of myocardial ischemia was established by a subcutaneous injection of isoproterenol (85 mg/kg) for two consecutive days. Conventional HE staining and Masson staining were performed for pathological changes. Biochemical indicators were measured by the enzyme-linked immuno sorbent assay (ELISA). Western blotting was used to measure the levels of related proteins in JNK/STAT signaling pathway.RESULTS: Compared to control group, the levels of CK-MB, TC, and TGs were significantly increased in model group. The levels of CK-MB, TC, and TGs in each Lyc-administered group were decreased. After Lyc was administered, the SOD, CAT, GSH-Px activities and MDA content were all restored. The serum levels of IL-1β, TNF-α and IL-6 in control group were significantly lower than in model group. When the Lyc was administered, the serum IL-1β, TNF-α and IL-6 levels in medium-dose group and high-dose group were significantly decreased. The levels of Bax/Bcl-2, Cyt-c, and Caspase-3 in model group were significantly higher than control group. Changes of Bax/Bcl-2, Cyt-c, and Caspase-3 in medium-dose and high-dose groups after the administration of Lyc were restored significantly. The levels of p-JNK/JNK, p-STAT1 (Tyr701)/STAT1, p-STAT1 (Ser727)/STAT1, p-STAT3 (Tyr705)/STAT3 were significantly increased, while p-STAT3 (Ser727)/STAT3 was significantly decreased. When Lyc was administered, the expression levels of p-JAK/JAK, p-STAT1 (Tyr701)/STAT1, p-STAT1 (Ser727)/STAT1, p-STAT3 (Tyr705)/STAT3 protein in medium-dose group and high-dose group were significantly decreased, and the expression level of p-STAT3 (Ser727)/STAT3 protein was significantly increased.CONCLUSIONS: Lyc could show a protective effect on oxidative stress injury and anti-cardiomyocyte apoptosis of myocardial ischemia, and its possible mechanism was to attenuate the activation of JNK/ERK signaling pathway induced by myocardial injury.

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PMID: 

J Food Sci. 2019 May ;84(5):1194-1200. Epub 2019 Apr 23. PMID: 31012961

Abstract Title: 

Lycopene Ameliorated Oxidative Stress and Inflammation in Type 2 Diabetic Rats.

Abstract: 

We aim to study the antioxidative and anti-inflammatory effects of lycopene on type 2 diabetes mellitus (T2DM) rats, anticipating a complementary strategy for the prevention of long-term complications of T2DM. In this study, rats with streptozotocin-induced diabetes were divided into four groups, receiving a 10-week lycopene intervention: DM, DM + low dose of lycopene (L), DM + medium dose of lycopene (M), and DM + high dose of lycopene (H) group with 0, 5, 10, and 15 mg/kg BW lycopene, respectively. At the end of intervention, fasted blood glucose (FBG) level, oxidative stress indicators, including glycosylated hemoglobin (GHb), glycosylated low-density lipoprotein, oxidized low-density lipoprotein (ox-LDL). and malondialdehyde (MDA), as well as antioxidants,that is, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and inflammatory factors like tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were determined. The results indicated that oxidative stress and inflammatory factors were elevated in DM rats. Lycopeneintervention decreased the FBG level in DM rats compared with the untreated ones. It revealed a dose-dependent effect on decreasing serum oxidative stress biomarkers, including GHb, ox-LDL, and MDA. Inflammatory factors (TNF-α and CRP) in DM rats were also decreased by lycopene intervention. Totalantioxidative capacity as well as the activities of antioxidants in DM rats including CAT, SOD, and GPx were increased after lycopene intervention. We conclude that lycopene protects against diabetic progression and prevents further complications of diabetic rats through ameliorating oxidative stress and inflammation, as well as improving the systemic antioxidative capacity. PRACTICAL APPLICATION: According to our study, lycopene intakes at experimental dosages appear to have beneficial effects on ameliorating oxidative stress and inflammation in type 2 diabetes mellitus (T2DM) rats, suggesting that lycopene might help improving T2DM progression when its daily intake is up to about 0.79 mg/kg BW in humans, which approximately equals to 5 mg/kg BW in rats. However, more clinical trials are needed to provide a more reliable and convincing conclusion in humans.

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PMID: 

Int J Mol Med. 2019 Jun ;43(6):2451-2461. Epub 2019 Apr 15. PMID: 31017253

Abstract Title: 

Lycopene restores the effect of ischemic postconditioning on myocardial ischemia‑reperfusion injury in hypercholesterolemic rats.

Abstract: 

Ischemic postconditioning (IPoC) has been demonstrated to prevent myocardial ischemia‑reperfusion injury (MIRI), but its cardioprotective effect is abrogated by hypercholesterolemia. The aim of the present study was to determine whether lycopene (LP), a type of carotenoid, can restore the cardioprotective effect of IPoC in hypercholesterolemic rats. Male Wistar rats were fed a cholesterol‑enriched diet for 12 weeks to establish a hypercholesterolemic model. The rat hearts were isolated and subjected to 30 min ischemia and 60 min reperfusion using a Langendorff apparatus. LP was administered to the rats intraperitoneally for 5 consecutive days prior to ischemia and reperfusion. Myocardial pathological changes, infarct size and cell apoptosis were measured by hematoxylin and eosin, triphenyltetrazolium chloride and TUNEL staining, respectively. The changes in endoplasmic reticulum (ER) stress markers, the reperfusion injury salvage kinase (RISK) pathway and mitochondrial apoptosis‑related proteins were detected by western blotting. Overall, the results demonstrated that low‑dose LP in combination with IPoC ameliorated myocardial histopathological changes, reduced the infarct size and release of cardiac enzymes, and decreased cardiomyocyte apoptosis in hypercholesterolemic rats, but no beneficial effects were achieved by the same dose of LP or IPoC treatment were used alone. Furthermore, the combination of LP and IPoC inhibited the expression of glucose‑regulated protein 78 and C/EBP homologous protein, increased the phosphorylation levels of AKT, ERK1/2 and glycogen synthase kinase‑3β, repressed mitochondrial permeability transition pore opening, and reduced the expression of cytochrome c, cleaved caspase‑9 and cleaved caspase‑3. Collectively, these findings demonstrated that LP can restore the cardioprotective effects of IPoC on MIRI inhypercholesterolemic rats, and this restoration by LP was mediated by inhibition of ER stress and reactivation of the RISK pathway in hypercholesterolemic rat myocardium.

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PMID: 

J Nutr Biochem. 2019 Jul ;69:63-72. Epub 2019 Apr 4. PMID: 31060024

Abstract Title: 

Lycopene supplementation attenuates western diet-induced body weight gain through increasing the expressions of thermogenic/mitochondrial functional genes and improving insulin resistance in the adipose tissue of obese mice.

Abstract: 

This passive overconsumption of western diet has precipitated a steep rise in obesity and its comorbidities, and obesity has become one of the main threats to health worldwide. Thus, deciphering the molecular mechanisms leading to obesity is therefore of utmost importance to guide the search for novel therapeutic and preventive strategies. Lycopene (LYC), a major carotenoid present in tomato, has been regarded as a nutraceutical that has powerful anti-oxidant and anti-obesity bioactivities. Even though substantial progress has been made in deciphering the mechanism of how LYC affects obesity in recent years, whether thermogenic genes, mitochondrial function and insulin resistance are involved in the anti-obesity effect of LYC is yet to be elucidated. In the current study, we demonstrated that LYC remarkably suppressed HFFD-elevated mice body weight gain. LYC blocked lipid accumulation in adipose tissue by decreasing the expressions of lipogenesis genes and increasing the expressions of lipidolysis related genes, including thermogenic and mitochondrial functional genes. Moreover, LYC improved HFFD-induced insulin resistance in WATs via inhibiting the inflammation responses in WATs, decreasing circulating proinflammatory cytokines, suppressing gut leak and intestinal inflammation. Our study indicating that the supplementation of LYC might be a nutritional preventive strategy to combat obesity.

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PMID: 

Nutrients. 2019 May 17 ;11(5). Epub 2019 May 17. PMID: 31108934

Abstract Title: 

Dietary Carotenoids and Non-Alcoholic Fatty Liver Disease among US Adults, NHANES 2003⁻2014.

Abstract: 

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Oxidative stress is thought to be a major mechanism, and previous epidemiological studies found higher serum levels of antioxidant carotenoids were associated with reduced risk for development and progression of NAFLD. The objective of this analysis is to examine cross-sectional associations between dietary and serum levels of carotenoids in relation to NAFLD among a nationally representative sample of US adults. We used data from the 2003-2014 National Health and Nutrition Examination Survey (NHANES). Dietary carotenoid intake was estimated from a 24-hour recall, while serum carotenoids were measured from 2003 to 2006. The NAFLD status was determined based upon US Fatty Liver Index (FLI) value≥30. Regression models were used to estimate associations between carotenoids and NAFLD by controlling for covariates and adjusting for survey design variables. Overall, 33% of participants were classified as having NAFLD. Intake of all carotenoids, with the exception of lycopene, was lower amongthose with NAFLD. This association was significant for the highest quartiles of intake of α-carotene, β-carotene, β-cryptoxanthin, and lutein/zeaxanthin. For serum measures, the highest level of all carotenoids was associated with significantly reduced odds of NAFLD. In conclusion, higher intakeand serum levels of most carotenoids were associated with lower odds of having NAFLD. Identification of such modifiable lifestyle factors provide an opportunity to limit or prevent the disease and its progression.

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PMID: 

Ann Anat. 2019 Jul ;224:142-152. Epub 2019 May 17. PMID: 31108192

Abstract Title: 

Lycopene protects against renal cortical damage induced by nandrolone decanoate in adult male rats.

Abstract: 

Nandrolone decanoate is an anabolic androgenic steroid that is abused worldwide by young athletes and bodybuilders to enhance their physical performance. Many clinical reports among those abusers demonstrated a variety of renal disorders. Lycopene is one of the dietary carotenoids found in fruits like tomato, watermelon, and grapefruit and has attracted considerable attention as an antioxidant. Therefore, the present study was designed to evaluate the protective effect of lycopene against nandrolone decanoate induced renal cortical damage. Forty adult male rats were equally divided into four main groups: group I served as the control, group II received lycopene 4 mg/kg/day, group III received nandrolone 10 mg/kg/week, and group IV received nandrolone and lycopene at a dose similar to the previous groups. At the end of the experiment, urea, creatinine and oxidative stress indicators were measured, then the kidneys were sampled for histopathological and immunohistochemical studies. Sections of the group (ПI) showed variable histopathological alterations in the form of distorted shrunken glomeruli and almost complete loss of the glomerular capillaries, in addition to vacuolation and shedding of the tubular epithelium. In conclusion, these results showed that nandrolone decanoate induced toxic effects in the kidney of rats and lycopene had protective effects versus such evoked renal damage.

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PMID: 

Radiat Environ Biophys. 2019 08 ;58(3):425-432. Epub 2019 May 23. PMID: 31123854

Abstract Title: 

The effect of lycopene supplementation on radiation-induced micronuclei in mice reticulocytes in vivo.

Abstract: 

Lycopene (LYC) is a natural pigment present in tomatoes and other red fruits and vegetables including red carrots, red peppers, watermelons, pink grapefruits, apricots, pink guavas, and papaya. There is some evidence that LYC may provide protection against mutations induced by ionizing radiation. The study aimed to investigate whether the genetic material of reticulocytes (RET) could be protected from radiation-induced damage by LYC. Mice were treated with LYC [0.15 mg/kg bodyweight (bw), 0.30 mg/kg bw], acute and fractionated irradiation (0.5 Gy, 1 Gy applied daily), or with both agents (0.5 Gy + 0.15 mg/kg bw LYC, 0.5 Gy + 0.30 mg/kg bw LYC, 1 Gy + 0.15 mg/kg bw LYC, 1 Gy + 0.30 mg/kg LYC). LYC supplementation was started at 24 hor 1 week after the first irradiation. Irradiation significantly enhanced the frequency of micronuclei (MN) in RET. LYC treatment at a dose of 0.15 mg/kg bw 24 h after starting fractionated radiation at 1 Gy significantly decreased (41-68%, p  0.24) to those obtained with irradiation alone. Lycopene may act as a radiomitigator but must be administered at low doses and as soon as possible after irradiation. Contrary, combined exposure with high doses of irradiation and LYC may enhance the mutagenic effect of irradiation.

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