PMID: 

Am J Physiol. 1991 Apr ;260(4 Pt 1):E537-43. PMID: 2018119

Abstract Title: 

Transferrin enhances the antiproliferative effect of aluminum on osteoblast-like cells.

Abstract: 

Aluminum (Al) retention in the body can cause metabolic bone disease. This disorder is characterized by reductions in the number of osteoblasts, a feature that suggests a disturbance in bone cell proliferation or differentiation. Because Al as well as iron (Fe) can bind to transferrin (TF) in plasma, the role of TF as a modifier of osteoblast proliferation was examined in UMR-106-01 osteoblast-like cells by measuring the incorporation of tritiated thymidine ([3H]-TdR) into DNA (counts.min-1.microgram cell protein-1, means +/- SE) during 48-h incubations in serum-free medium (SFM). In the absence of TF, DNA synthesis decreased when media levels of Al exceeded 6-10 microM. The mitogenic response to physiological levels of unsaturated TF (apo-TF) was attenuated however during incubations with TF that was partially saturated with Al (Al-TF). A similar inhibitory response was seen in cells incubated with the antiproliferative agent gallium (Ga) when added to SFM as partially saturated Ga-TF. TF produced a shift to the left in the inhibitory dose-response curve to Al in osteoblast-like cells; thus, DNA synthesis decreased at substantially lower media concentrations of Al in cells grown in SFM containing partially saturated Al-TF. The results indicate that TF is an important determinant of the inhibitory effect of Al on DNA synthesis by osteoblast-like cells at the micromolar levels of Al that can occur in plasma in vivo.

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PMID: 

J Inorg Biochem. 2001 Nov ;87(1-2):9-14. PMID: 11709207

Abstract Title: 

Aluminium toxicity and iron homeostasis.

Abstract: 

In an animal model of aluminum overload, (aluminium gluconate), the increases in tissue aluminium content were paralleled by elevations of tissue iron in the kidney, liver heart and spleen as well as in various brain regions, frontal, temporal and parietal cortex and hippocampus. Despite such increases in iron content there were no significant changes in the activities of a wide range of cytoprotective enzymes apart from an increase in superoxide dismutase in the frontal cortex of the aluminium loaded rats. Such increases in tissue iron content may be attributed to the stabilisation of IRP-2 by aluminium thereby promoting transferrin receptor synthesis while blocking ferritin synthesis. Using the radioactive tracer (26)Al less than 1% of the injected dose was recovered in isolated ferritin, supporting previous studies which also found little evidence for aluminium storage within ferritin. The increases in brain iron may well be contributory to neurodegeneration, although the pathogenesis by which iron exerts such an effect is unclear.

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PMID: 

Biochem J. 1990 Dec 1 ;272(2):377-82. PMID: 2268267

Abstract Title: 

Effect of aluminium on iron uptake and transferrin-receptor expression by human erythroleukaemia K562 cells.

Abstract: 

Incubation of human erythroleukaemia K562 cells with Al-transferrin inhibited iron uptake from 59Fe-transferrin by about 80%. The inhibition was greater than that produced by a similar quantity of Fe-transferrin. Preincubation of cells for 6 h with either Al-transferrin or Fe-transferrin diminished the number of surface transferrin receptors by about 40% compared with cells preincubated with apo-transferrin. Al-transferrin did not compete significantly with Fe-transferrin for transferrin receptors and, when cells were preincubated for 15 min instead of 6 h, the inhibitory effect of Al-transferrin on receptor expression was lost. Both forms of transferrin also decreased the level of transferrin receptor mRNA by about 50%, suggesting a common regulatory mechanism. Aluminium citrate had no effect on iron uptake or transferrin-receptor expression. AlCl3 also had no effect on transferrin-receptor expression, but at high concentration it caused an increase in iron uptake by an unknown, possibly non-specific, mechanism. Neither Al-transferrin nor AlCl3 caused a significant change in cell proliferation. It is proposed that aluminium, when bound to transferrin, inhibits iron uptake partly by down-regulating transferrin-receptor expression and partly by interfering with intracellular release of iron from transferrin.

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PMID: 

J Biochem. 1998 Jan ;123(1):42-6. PMID: 9504407

Abstract Title: 

Aluminum taken up by transferrin-independent iron uptake affects the iron metabolism in rat cortical cells.

Abstract: 

We previously demonstrated that cultured human fibroblasts internalize iron via transferrin-independent iron uptake (Tf-IU), redox, and receptor-mediated endocytosis uptake systems [Oshiro, S., Nakajima, H., Markello, T., Krasnewich, D., Bernardini, I., and Gahl, W.A. (1993) J. Biol. Chem. 268, 21586 21591]. Of these iron transport systems, the Tf-IU system is involved in the accumulation of transition metals in various mammalian cells. It is also known that in experimental animals fed aluminum (Al), Al at micromolar level selectively accumulates in the brain. In the present study, we examined the effects of Al accumulated in the brain cells on iron transport by the Tf-IU system and iron metabolism, using primary cultures from fetal rat cerebral cortex. Pretreatment of cells with 200 microM Al-nitrilotriacetate upregulated the Tf-IU system for iron. Moreover, of various metals tested, Al markedly upregulated the Tf-IU activity. To examine the influence of Al on iron metabolism, the interaction between Al accumulated in the cells and iron-responsive element binding protein (IRE-BP), a cellular iron regulator, was examined by Northern blot analysis, and activity assay: Al decreased the Tf receptor mRNA level and increased the aconitase activity of IRE-BP. The increase of aconitase activity by Al was also observed in vitro. These results suggest that Al accumulated in cortical cells affects iron metabolism.

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PMID: 

Cell Immunol. 2016 Jun-Jul;304-305:35-43. Epub 2016 May 14. PMID: 27212461

Abstract Title: 

Th1 versus Th2 T cell polarization by whole-cell and acellular childhood pertussis vaccines persists upon re-immunization in adolescence and adulthood.

Abstract: 

The recent increase in cases of whooping cough among teenagers in the US suggests that the acellular Bordetella pertussis vaccine (aP) that became standard in the mid 1990s might be relatively less effective than the whole-bacteria formulation (wP) previously used since the 1950s. To understand this effect, we compared antibody and T cell responses to a booster immunization in subjects who received either the wP or aP vaccine as their initial priming dose in childhood. Antibody responses in wP- and aP-primed donors were similar. Magnitude of T cell responses was higher in aP-primed individuals. Epitope mapping revealed the T cell immunodominance patterns were similar for both vaccines. Further comparison of the ratios of IFNγ and IL-5 revealed that IFNγ strongly dominates the T cell response in wP-primed donors, while IL-5 is dominant in aP primed individuals. Surprisingly, this differential pattern is maintained after booster vaccination, at times from eighteen years to several decades after the original aP/wP priming. These findings suggest that childhood aP versus wP vaccination induces functionally different T cell responses to pertussis that become fixed and are unchanged even upon boosting.

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PMID: 

J Agric Food Chem. 2018 Dec 19 ;66(50):13173-13182. Epub 2018 Dec 5. PMID: 30474364

Abstract Title: 

The Dose-Response Effect of Lycopene on Cerebral Vessel and Neuron Impairment Induced by Hyperlipidemia.

Abstract: 

To study the dose-response effect of lycopene on vessel and neuron damage in the brain against hyperlipidemia, rats were fed with hypercholesterolemic feed and treated with lycopene orally by gavage at the dose of 5, 25, 45, 65, 85, and 105, 125 mg/kg/bw/d. At the end of the fourth week, lycopene doses and serum lycopene concentration showed an inverse U-shape curve. Serum lycopene concentration was negatively correlated with the levels of serum TC, TG, LDL-C, as well as the cerebral LDL-C, VEGF, and VCAM-1. Serum lycopene concentration was positively correlated with the expression of Claudin-5 and the number of neurons in hippocampal CA1 and CA3. Lycopene could also reduce the pathologic change of these areas. These results suggested an inverse U-shape relation between dose and serum concentration of lycopene, and intermediate doses were most effective to protect cerebral vessels and neurons from being damaged by hyperlipidemia.

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PMID: 

Adv Nutr. 2019 01 1 ;10(1):19-29. PMID: 30475939

Abstract Title: 

Lycopene and Metabolic Syndrome: A Systematic Review of the Literature.

Abstract: 

Cardiometabolic risk factors increase the likelihood of cardiovascular disease development by 2-fold. Lycopene, a potent lipophilic antioxidant, may be able to mediate oxidative stress, a mechanism underpinning metabolic syndrome (MetS) and its risk factors. This is, to our knowledge, the first systematic review of the literature with the purpose of investigating the relation between circulating lycopene or dietary intake of lycopene and MetS as well as its risk factors. The review was conducted using PubMed and EBSCOhost databases with the search terms"lycopene"and"metabolic syndrome." Inclusion criteria included human studies published in English in a scholarly, peer-reviewed journal and evaluation of lycopene in relation to ≥3 of the 5 MetS risk factors as defined by the National Cholesterol Education Program's Adult Treatment Panel III (ATP III) report. The process identified 11 studies, including 8 cross-sectional and 3 intervention studies. Cross-sectional studies were grouped into 3 categories, with several studies falling into>1 category, based on results reporting associations of lycopene with the prevalence and outcomes of MetS (5 studies), presence of ATP III risk factors (4 studies), and variables mediating lycopene's influence on MetS risk (3 studies). All studies in each category reported significant protective associations. Of the 3 intervention studies, all reported significant protective effects from a lycopene-rich beverage, despite varying doses and durations of intake. Although a protective relation between lycopene and MetS was generally supported, different MetS components appeared to be influenced by lycopene rather than demonstrating consistent improvement in a single component. Thus, additional research is needed to elucidate the mechanistic effects of lycopene on MetS, as well as to determine evidence-based recommendations concerning dose-durational effects of lycopene and MetS risk reduction. In conclusion, the evidence of lycopene's benefit exists such that lycopene status or lycopene consumption may be associated with favorable alterations to the components of MetS.

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PMID: 

Int J Obes (Lond). 2019 09 ;43(9):1735-1746. Epub 2018 Dec 11. PMID: 30538283

Abstract Title: 

Lycopene attenuates western-diet-induced cognitive deficits via improving glycolipid metabolism dysfunction and inflammatory responses in gut-liver-brain axis.

Abstract: 

BACKGROUND/OBJECTIVES: The aim of the current study was to investigate the inhibitory effect of lycopene (LYC), a major carotenoid present in tomato, on high-fat and high-fructose western diet (HFFD)-induced cognitive impairments and the protective effects on HFFD-elicited insulin resistance, lipid metabolism dysfunction and inflammatory responses in the gut-liver-brain axis.SUBJECTS/METHODS: We randomly assigned 3-month-old C57BL/6 J mice to three groups with different diets: the control group, HFFD group and HFFD + LYC group (LYC, 0.03% w/w, mixed into high-fat diet) for 10 weeks.RESULTS: The results of the Y-maze task and Morris water maze tests demonstrated that LYC attenuated HFFD-induced memory loss. Moreover, LYC suppressed HFFD-elicited synaptic dysfunction and increased the expressions of SNAP-25 and PSD-95. Furthermore, LYC ameliorated insulin resistance, lipid metabolism dysfunction and inflammatory responses in the mouse brain and liver. LYC also prevente.d intestinal barrier integrity damages and decreased the level of circulating LPS.CONCLUSIONS: These results demonstrated that LYC ameliorated HFFD-induced cognitive impairments in a mouse model by improving insulin resistance, lipid metabolism dysfunction and inflammatory responses in the gut-liver-brain axis. These findings indicate that LYC might be a nutritional strategy for western diet-induced dysfunction of the central nervous system.

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PMID: 

Biomed Pharmacother. 2019 Jan ;109:2070-2077. Epub 2018 Nov 26. PMID: 30551463

Abstract Title: 

Effects of lycopene on metabolism of glycolipid in type 2 diabetic rats.

Abstract: 

Diabetes is a series of metabolic diseases, which characteristics is hyperglycemia caused by the interruption of insulin action. Lycopene is an antioxidant which has potential anti-diabetic activity but the correlative reports are rare. This study was designed to explore the influence of lycopene on metabolism of glycolipid in type 2 diabetes. The model of type2 diabetes was induced in adult male albino Sprague Dawley rats, weighing 180-220 g, feeding high fat diet for 4 weeks, then streptozotocin (25 mg/kg) was intraperitoneally injected. 1 week after, rats in diabetic group showed increasing in fasting blood glucose, lipid in blood and liver, glycosylated hemoglobin, HOMA-IR and decreasing in plasma insulin comparing with the normal control group after modeling. Oral administration of lycopene oil solution (10 mg/kg or 20 mg/kg body weight) once a day for 10 weeks can improve the above changes and make them toward to normality. The activities of oxidative enzymes SOD and GSH-Px increased and MDA decreased in pancreatictissue of rats after the intervention of lycopene. In addition, it can also observe that lycopene can protect body weight loss from diabetic rats. These results showed that lycopene has potential effect on anti-diabetes and it can regulate the metabolism of glycolipid in diabetic rats.

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PMID: 

Biomed Pharmacother. 2019 Mar ;111:791-801. Epub 2019 Jan 4. PMID: 30616078

Abstract Title: 

A review for the pharmacological effect of lycopene in central nervous system disorders.

Abstract: 

Lycopene is an aliphatic hydrocarbon carotenoid extracted from plants like tomatoes, papayas, and watermelons. Previous studies have shown that lycopene can exert prophylactic and/or therapeutic effects in different disorders, such as heart failure and neoplasm via anti-oxidative, anti-inflammatory, and anti-proliferative activities. In the central nervous system (CNS), lycopene also has prophylactic and/or therapeutic effects in different type of disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), cerebral ischemia, epilepsy, and depression. Lycopene also improves cognition and memory ability of rodents in different pathological conditions, such as diabetes, colchicine exposure, high-fat diet (HFD), and aging. Further, lycopene can prevent neuro-toxicities induced by monosodium glutamate (MSG), trimethyltin (TMT), methylmercury (MeHg), tert-butyl hydroperoxide (t-BHP), and cadmium (Cd). In some special conditions such as ethanol addiction and haloperidol-induced orofacial dyskinesia, lycopene administration displays special therapeutic effects. Mechanisms including inhibition of oxidative stress and neuroinflammation, inhibition of neuronal apoptosis, and restoration of mitochondrial function have been shown to mediate the neuroprotective effects of lycopene. Other mechanisms, such as inhibition of nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK), activation of the nuclear factor erythroid 2-related factor (Nrf2) and brain-derived neurotrophic factor (BDNF) signaling, and restoration of intracellular Cahomeostasis, may be also involved in the neuroprotective effect of lycopene. In hope of get a clear impression about the role of lycopene in the CNS, we summarize and discuss the pharmacological effects of lycopene as well as its possible mechanisms in CNS disorder prevention and/or therapy.

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