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1.
Molecules ; 26(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34361546

RESUMO

The adsorption of retinol, niacinamide and glycolic acid active ingredients on the internal surface of halloysite in an aqueous environment was explored at the molecular level by means of calculations based on quantum mechanics and force fields from empirical interatomic potentials. These active ingredients are stably adsorbed on the internal surface of halloysite forming hydrogen bonds between the hydrogen, oxygen and nitrogen atoms with the hydroxyl groups of the inner surface of the halloysite. In addition, electrostatic interaction between these active ingredients with the water molecules was observed. Therefore, the theoretical results indicate that the adsorption of these active principles is favourable in the halloysite nanotube, which allows directing future experimental investigations for the development and design of retinol, niacinamide and glycolic acid with halloysite nanotubes systems, which may be topical formulations for skincare.


Assuntos
Argila/química , Glicolatos , Niacinamida , Higiene da Pele , Vitamina A , Administração Tópica , Glicolatos/química , Glicolatos/farmacologia , Humanos , Niacinamida/química , Niacinamida/farmacologia , Vitamina A/química , Vitamina A/farmacologia
2.
Gene ; 799: 145811, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34224829

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the brain. α-Synuclein is an aggregation-prone neural protein that plays a role in the pathogenesis of PD. In our previous paper, we found that saffron; the stigma of Crocus sativus Linné (Iridaceae), and its constituents (crocin and crocetin) suppressed aggregation of α-synuclein and promoted the dissociation of α-synuclein fibrils in vitro. In this study, we investigated the effect of dietary saffron and its constituent, crocetin, in vivo on a fly PD model overexpressing several mutant α-synuclein in a tissue-specific manner. Saffron and crocetin significantly suppressed the decrease of climbing ability in the Drosophila overexpressing A30P (A30P fly PD model) or G51D (G51D fly PD model) mutated α-synuclein in neurons. Saffron and crocetin extended the life span in the G51D fly PD model. Saffron suppressed the rough-eyed phenotype and the dispersion of the size histogram of the ocular long axis in the eye of A30P fly PD model. Saffron had a cytoprotective effect on a human neuronal cell line with α-synuclein fibrils. These data showed that saffron and its constituent crocetin have protective effects on the progression of PD disease in animals in vivo and suggest that saffron and crocetin can be used to treat PD.


Assuntos
Carotenoides/farmacologia , Crocus/química , Atividade Motora/efeitos dos fármacos , Doença de Parkinson/etiologia , Degeneração Retiniana/tratamento farmacológico , Vitamina A/análogos & derivados , Animais , Animais Geneticamente Modificados , Linhagem Celular , Modelos Animais de Doenças , Drosophila melanogaster/genética , Feminino , Humanos , Longevidade/efeitos dos fármacos , Masculino , Mutação , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Degeneração Retiniana/etiologia , Degeneração Retiniana/fisiopatologia , Vitamina A/farmacologia , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , alfa-Sinucleína/toxicidade
3.
Aging (Albany NY) ; 13(12): 15785-15800, 2021 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-34176789

RESUMO

Recent reports indicate that patients with hepatocholangiocarcinoma (CHOL) have a higher morbidity and mortality rate for coronavirus disease (COVID-19). Anti-CHOL/COVID-19 medicines are inexistent. Vitamin A (VA) refers to a potent nutrient with anti-cytotoxic and anti-inflammatory actions. Therefore, this study aimed to determine the potential functions and molecular mechanisms of VA as a potential treatment for patients with both CHOL and COVID-19 (CHOL/COVID-19). The transcriptome data of CHOL patients were obtained from the Cancer Genome Analysis database. Furthermore, the network pharmacology approach and bioinformatics analysis were used to identify and reveal the molecular functions, therapeutic biotargets, and signaling of VA against CHOL/COVID-19. First, clinical findings identified the medical characteristics of CHOL patients with COVID-19, such as susceptibility gene, prognosis, recurrence, and survival rate. Anti-viral and anti-inflammatory pathways, and immunopotentiation were found as potential targets of VA against CHOL/COVID-19. These findings illustrated that VA may contribute to the clinical management of CHOL/COVID-19 achieved by induction of cell repair, suppression of oxidative stress and inflammatory reaction, and amelioration of immunity. Nine vital therapeutic targets (BRD2, NOS2, GPT, MAPK1, CXCR3, ICAM1, CDK4, CAT, and TMPRSS13) of VA against CHOL/COVID-19 were identified. For the first time, the potential pharmacological biotargets, function, and mechanism of action of VA in CHOL/COVID-19 were elucidated.


Assuntos
COVID-19/tratamento farmacológico , Imunidade/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Vitamina A/farmacologia , Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , COVID-19/virologia , Carcinoma Hepatocelular/genética , Colangiocarcinoma/genética , Biologia Computacional , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Neoplasias Hepáticas/genética , Masculino , Simulação de Acoplamento Molecular , Modelos de Riscos Proporcionais , Transdução de Sinais/efeitos dos fármacos
4.
Nutrients ; 13(3)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806806

RESUMO

In diabetes mellitus type 2 (DM2), developed obesity is referred to as diabesity. Implementation of a healthy diet, such as the Mediterranean, prevents diabesity. Saffron is frequently used in this diet because of its bioactive components, such as crocetin (CCT), exhibit healthful properties. It is well known that obesity, defined as an excessive accumulation of fat, leads to cardiometabolic pathology through adiposopathy or hypertrophic growth of adipose tissue (AT).This is related to an impaired adipogenic process or death of adipocytes by obesogenic signals. We aimed to evaluate the effect of the pathogenic microenvironment and CCT, activating differentiation of healthy preadipocytes (PA). For this, we used human cryopreserved PA from visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) depots obtained from healthy and obese-DM2 donors. We studied the effect of a metabolically detrimental (diabesogenic) environment, generated by obese-DM2 adipocytes from VAT (VdDM) or SAT (SdDM), on the viability and accumulation of intracellular fat of adipocytes differentiated from healthy PA, in the presence or absence of CCT (1 or 10 µM). Intracellular fat was quantified by Oil Red O staining. Cytotoxicity was measured using the MTT assay. Our results showed that diabesogenic conditions induce cytotoxicity and provide a proadipogenic environment only for visceral PA. CCT at 10 µM acted as an antiadipogenic and cytoprotective compound.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/citologia , Carotenoides/farmacologia , Diferenciação Celular , Diabetes Mellitus/tratamento farmacológico , Obesidade/tratamento farmacológico , Vitamina A/farmacologia , Adipócitos/patologia , Adipogenia , Adipocinas , Animais , Linhagem Celular , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Humanos , Gordura Intra-Abdominal , Masculino , Obesidade/sangue , Obesidade/patologia , Ratos , Gordura Subcutânea , Vitamina A/análogos & derivados
5.
Int J Mol Sci ; 22(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805295

RESUMO

Bladder cancer (BC) is the tenth most common cancer worldwide with a high recurrence rate, morbidity and mortality. Therefore, chemoprevention and improved treatment of BC are of paramount importance. Epidemiological studies suggest that adequate vitamin A intake may be associated with reduced BC risk. In addition, retinoids, natural and synthetic derivatives of vitamin A, are intensively studied in cancer research due to their antioxidant properties and their ability to regulate cell growth, differentiation, and apoptosis. Findings from in vivo and in vitro models of BC show great potential for the use of retinoids in the chemoprevention and treatment of BC. However, translation to the clinical practice is limited. In this narrative review we discuss: (i) vitamin A and retinoid metabolism and retinoic acid signalling, (ii) the pathobiology of BC and the need for chemoprevention, (iii) the epidemiological evidence for the role of dietary vitamin A in BC, (iv) mechanistic insights obtained from in vivo and in vitro models, (v) clinical trials of retinoids and the limitations of retinoid use, (vi) novel systems of retinoid delivery, and (vii) components of retinoid signalling pathways as potential novel therapeutic targets.


Assuntos
Anticarcinógenos/uso terapêutico , Antineoplásicos/uso terapêutico , Retinoides/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vitamina A/metabolismo , Animais , Apoptose , Diferenciação Celular , Humanos , Retinoides/farmacologia , Retinoides/uso terapêutico , Transdução de Sinais , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/fisiopatologia , Neoplasias da Bexiga Urinária/prevenção & controle , Vitamina A/farmacologia , Vitamina A/uso terapêutico
6.
Molecules ; 26(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802807

RESUMO

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 µM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.


Assuntos
Carotenoides/farmacologia , Fertilidade/efeitos dos fármacos , Puberdade/efeitos dos fármacos , Lesões por Radiação/tratamento farmacológico , Testículo/efeitos dos fármacos , Vitamina A/análogos & derivados , Animais , Autofagia/efeitos dos fármacos , Autofagia/efeitos da radiação , Carotenoides/uso terapêutico , Catalase/metabolismo , Células Cultivadas , Regulação para Baixo , Proteína Semelhante a ELAV 1/metabolismo , Fertilidade/efeitos da radiação , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos da radiação , Imuno-Histoquímica , Técnicas In Vitro , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Poli(ADP-Ribose) Polimerase-1/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Puberdade/efeitos da radiação , Túbulos Seminíferos/citologia , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/efeitos da radiação , Sirtuína 1/metabolismo , Superóxido Dismutase/metabolismo , Testículo/efeitos da radiação , Regulação para Cima , Vitamina A/farmacologia , Vitamina A/uso terapêutico , Raios X
7.
Yakugaku Zasshi ; 141(4): 557-577, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33790122

RESUMO

"Retinoid" is the general term for vitamin A derivatives and chemical compounds that act like vitamin A. Vitamin A are composed of four isoprene units and are named according to their terminal functional group, such as retinol (OH, 1), retinal (CHO, 2), and retinoic acid (CO2H, 3). Vitamin A usually refers to retinol. In the past few decades, major advances in research on vitamin A have improved our understanding of its fundamental roles and physiological significance in living cells. In this review, three types of chemical biology studies using vitamin A analogs are described: (1) conformational studies of the chromophore in retinal proteins (rhodopsin, phoborhodopsin, and retinochrome), especially the conformation around the cyclohexene ring; (2) structure-activity relationship studies of retinoic acid analogs to create new signaling molecules for activating nuclear receptors; and (3) development of a new channelrhodopsin with an absorption maximum at longer wavelength to overcome the various demerits of channelrhodopsins used in optogenetics, as well as the stereoselective synthesis of retinoid isomers and their analogs using a diene-tricarbonyliron complex or a palladium-catalyzed cross-coupling reaction between vinyl triflates and stannyl olefins.


Assuntos
Vitamina A/análogos & derivados , Vitamina A/química , Alcenos/química , Catálise , Channelrhodopsins , Cicloexenos/química , Proteínas do Olho/química , Isomerismo , Mesilatos/química , Conformação Molecular , Reatores Nucleares , Paládio/química , Retinoides/síntese química , Retinoides/química , Estereoisomerismo , Relação Estrutura-Atividade , Compostos de Vinila/química , Vitamina A/farmacologia , Vitamina A/fisiologia
8.
BMC Genomics ; 22(1): 146, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653267

RESUMO

BACKGROUND: Retinol (RO) and its active metabolite retinoic acid (RA) are major regulators of gene expression in vertebrates and influence various processes like organ development, cell differentiation, and immune response. To characterize a general transcriptomic response to RA-exposure in vertebrates, independent of species- and tissue-specific effects, four publicly available RNA-Seq datasets from Homo sapiens, Mus musculus, and Xenopus laevis were analyzed. To increase species and cell-type diversity we generated RNA-seq data with chicken hepatocellular carcinoma (LMH) cells. Additionally, we compared the response of LMH cells to RA and RO at different time points. RESULTS: By conducting a transcriptome meta-analysis, we identified three retinoic acid response core clusters (RARCCs) consisting of 27 interacting proteins, seven of which have not been associated with retinoids yet. Comparison of the transcriptional response of LMH cells to RO and RA exposure at different time points led to the identification of non-coding RNAs (ncRNAs) that are only differentially expressed (DE) during the early response. CONCLUSIONS: We propose that these RARCCs stand on top of a common regulatory RA hierarchy among vertebrates. Based on the protein sets included in these clusters we were able to identify an RA-response cluster, a control center type cluster, and a cluster that directs cell proliferation. Concerning the comparison of the cellular response to RA and RO we conclude that ncRNAs play an underestimated role in retinoid-mediated gene regulation.


Assuntos
Tretinoína , Vitamina A , Animais , Humanos , Camundongos , Receptores do Ácido Retinoico/genética , Retinoides/farmacologia , Transcriptoma , Tretinoína/farmacologia , Vitamina A/farmacologia
9.
Nutrition ; 85: 111087, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33545543

RESUMO

OBJECTIVE: Vitamin A is commonly recommended as a treatment for diarrhea and undernutrition; however, little is known about the underlying cellular mechanisms. The aim of this study was to investigate the modulation of cell cycle by vitamin A derivatives (retinyl palmitate or retinol) in undernourished intestinal epithelial crypts (IEC-6). METHODS: IEC-6 cells were exposed to nutrient deprivation (no serum and no glutamine) and supplemented with retinyl palmitate or retinol at a range of 2 to 20 µM. Proliferation, apoptosis/necrosis, cell cycle process, and gene transcription were assessed. RESULTS: Nutrient deprivation for 6, 12, 24, or 48 h decreased cell proliferation, and retinyl palmitate further decreased it after 24 and 48 h. Apoptosis rates were reduced by undernourishment and further reduced by retinyl palmitate after 48 h; whereas necrosis rates were unaltered. Undernourishment induced overall cell quiescence, increased percentage of cells in G0/G1 phase and decreased percentage of cells in S phase after 12 h and in G2/M phases at 6, 12, and 24 h after treatment. Both retinoids also showed cell quiescence induction with less cells in G2/M phases after 48 h, whereas only retinol showed significant modulation of G0/G1 and S phases. Both retinoids also increased markers of cell differentiation Fabp and Iap gene transcriptions in about fivefold rates after 42 h. Furthermore, specific gene transcriptions related to MAP kinase signaling pathway regulation of cell differentiation and cell cycle regulation were triggered by retinoids in undernourished IEC-6, with higher levels of expression for Atf2 and C-jun genes. CONCLUSIONS: These findings indicated that both vitamin A derivatives induce further survival mechanisms in undernourished intestinal epithelial crypt cells. These mechanisms include increased cell quiescence, decreased apoptosis, increased cell differentiation, and transcription of genes related to MAP kinase signaling pathway.


Assuntos
Retinoides , Vitamina A , Ciclo Celular , Diferenciação Celular , Divisão Celular , Células Epiteliais , Nutrientes , Retinoides/farmacologia , Vitamina A/farmacologia
10.
Nutrients ; 13(2)2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33494277

RESUMO

Vitamin A is a fat-soluble vitamin that plays an important role in skin immunity. Deficiencies in Vitamin A have been linked to impaired immune response and increased susceptibility to skin infections and inflammatory skin disease. This narrative review summarizes recent primary evidence that elucidates the role of vitamin A and its derivatives on innate immune regulators through mechanisms that promote skin immunity and sustain the skin microbiome.


Assuntos
Imunidade Inata , Pele/imunologia , Vitamina A/imunologia , Animais , Dermatite , Humanos , Microbiota/fisiologia , Pele/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Tretinoína , Vitamina A/farmacologia , Deficiência de Vitamina A
11.
Nutrients ; 13(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466372

RESUMO

Animal studies as early as the 1920s suggested that vitamin A deficiency leads to squamous cell metaplasia in numerous epithelial tissues including the skin. However, humans usually die from vitamin A deficiency before cancers have time to develop. A recent long-term cohort study found that high dietary vitamin A reduced the risk of cutaneous squamous cell carcinoma (cSCC). cSCC is a form of nonmelanoma skin cancer that primarily occurs from excess exposure to ultraviolet light B (UVB). These cancers are expensive to treat and can lead to metastasis and death. Oral synthetic retinoids prevent the reoccurrence of cSCC, but side effects limit their use in chemoprevention. Several proteins involved in vitamin A metabolism and signaling are altered in cSCC, which may lead to retinoid resistance. The expression of vitamin A metabolism proteins may also have prognostic value. This article reviews what is known about natural and synthetic retinoids and their metabolism in cSCC.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Retinoides/farmacologia , Retinoides/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Estudos Clínicos como Assunto , Gerenciamento Clínico , Avaliação Pré-Clínica de Medicamentos , Resistência a Medicamentos , Humanos , Redes e Vias Metabólicas , Retinoides/metabolismo , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/etiologia , Resultado do Tratamento , Vitamina A/metabolismo , Vitamina A/farmacologia , Vitamina A/uso terapêutico
12.
J Ethnopharmacol ; 268: 113608, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33242618

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: This study aimed at determining the effects of saffron on depression as well as its neuroprotective and pharmacological effects on the intestinal function of crocetin in mice exposed to chronic restraint stress. MATERIALS AND METHODS: Chronic stress was induced in two-week-old ICR mice by immobilizing them for 6 h per day for 28 days. The mice were orally administered with crocetin (20, 40, 80 mg/kg), fluoxetine (20 mg/kg) or distilled water. The treatments were administered daily and open field and tail suspension tests were performed. Immunofluorescent and Western-bolt (WB) assays were conducted to determine the expression of mitogen-activated protein kinase phosphatase-1 (MKP-1), the precursor of brain-derived neurotrophic factor (proBDNF), extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated cAMP response element-binding (CREB) protein in the hippocampus. Serum levels of dopamine (DA), proBDNF, MKP-1 and CREB were measured by Elisa kits. High-throughput sequencing was carried out to analyze the composition of intestinal microbiota. RESULTS: Crocetin ameliorated depressive-like behaviors caused by chronic restraint stress-induced depressive mice. It significantly attenuated the elevated levels of MKP-1, proBDNF, alanine transaminase, aspartate transaminase and increased the serum levels of DA as well as CREB. Histopathological analysis showed that crocetin suppressed hippocampus injury in restraint stress mice by protecting neuronal cells. Immunofluorescent and WB analysis showed elevated expression levels of ERK1/2, CREB and inhibited expression levels of MKP-1, proBDNF in the hippocampus. The intestinal ecosystem of the crocetin group partially recovered and was close to the control group. CONCLUSIONS: Crocetin has neuroprotective properties and ameliorates the effects of stress-associated brain damage by regulating the MKP-1-ERK1/2-CREB signaling and intestinal ecosystem.


Assuntos
Antidepressivos/uso terapêutico , Carotenoides/uso terapêutico , Depressão/psicologia , Microbioma Gastrointestinal/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Psicológico/psicologia , Vitamina A/análogos & derivados , Animais , Antidepressivos/farmacologia , Carotenoides/farmacologia , Depressão/tratamento farmacológico , Microbioma Gastrointestinal/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Restrição Física/efeitos adversos , Restrição Física/psicologia , Estresse Psicológico/tratamento farmacológico , Vitamina A/farmacologia , Vitamina A/uso terapêutico
13.
Clin Exp Hypertens ; 43(2): 151-163, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33052059

RESUMO

AIMS: Vitamin A (VA) deficiency triggers many diseases and is a worldwide nutrition problem. The Retinol acyltransferase (LRAT) is an indicator of VA storage function, and the relationship between LRAT and blood pressure level and the regulation mechanism will be elucidated. METHODS: 160 children aged 6-12 years were included, and the serum VA and, the transcription levels of LRAT and RARs, were measured. Spontaneously hypertensive rats (SHRs) and WKY rats were treated with VA deficiency (VAD) or normal (VAN) fodder for 20 weeks. LRAT, retinoic acid, renin angiotensin system (RAS) biomarkers, and the structure and function of the heart for SHRs were measured. RESULTS: The serum retinol and serum retinol/BMI levels were lower in children in the low LRAT group (LRAT

Assuntos
Aciltransferases/metabolismo , Hipertensão , Sistema Renina-Angiotensina , Deficiência de Vitamina A , Vitamina A , Animais , Biomarcadores/metabolismo , Pressão Sanguínea/fisiologia , Criança , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Masculino , Ratos , Ratos Endogâmicos SHR , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Tretinoína/metabolismo , Vitamina A/sangue , Vitamina A/farmacologia , Deficiência de Vitamina A/diagnóstico , Deficiência de Vitamina A/metabolismo , Deficiência de Vitamina A/terapia , Vitaminas/sangue , Vitaminas/farmacologia
14.
Poult Sci ; 100(1): 174-185, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357679

RESUMO

A total of 2622 male broilers were distributed in a 2 × 5 factorial design, using 2 lipid sources (soybean oil and palm fat), 5 levels of vitamin A supplementation (0, 3,000, 6,000, 12,000, and 24,000 IU kg-1), with 10 replicates, and also 1 control diet (CD) for each lipid source used (7 replicates), each experimental unit being composed of 23 birds. During the first 21 d (how were the birds fed) and from 22 to 42 d of age, a redistribution of the treatments was carried out in a 2 × 2 × 5 factorial design: half of the repetitions of each treatment received the diet of the initial treatment, and the others received the CD with its type of lipid source. In the phase from 1 to 21 d of age, the effect of lipid source on feed intake (FI) and feed conversion ratio (FCR), and the effect of vitamin supplementation on FI and weight gain (WG) were observed, with a quadratic response for both variables. At 42 d of age, the lipid source and vitamin A level influenced the FI, whereas the WG and FCR showed interactions between period and the level of vitamin A supplementation. Neither lipid source resulted in blood parameters out of the typical pattern for birds, and the same was observed in relation to dietary vitamin A supplementation. From 1 to 21 d of age, a vitamin A supplementation of 15,585 IU kg-1 was estimated, and at 42 d, 15,527 IU kg-1 and 15,148 IU kg -1 were estimated for the periods 1 to 21 d and 1 to 42 d, respectively.


Assuntos
Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Desenvolvimento Ósseo , Gorduras Insaturadas na Dieta , Suplementos Nutricionais , Vitamina A , Ração Animal/análise , Animais , Desenvolvimento Ósseo/efeitos dos fármacos , Galinhas/sangue , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Dieta/veterinária , Gorduras Insaturadas na Dieta/farmacologia , Masculino , Distribuição Aleatória , Vitamina A/farmacologia , Vitaminas/farmacologia
15.
Nutr Rev ; 79(1): 76-87, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33301001

RESUMO

Vitamin A (VA) and its pro-vitamin carotenoids are naturally occurring lipophilic compounds involved in several cellular processes and metabolic pathways. Despite their broad spectrum of activities in the general population, dietary deficiencies of these compounds can potentially affect pregnancy outcomes. Since maternal nutritional status and diet composition during pregnancy and lactation can have long-lasting effects in offspring until adulthood, this study presents an overview of VA and the role of pro-VA carotenoids during pregnancy and lactation - the nutrition, metabolism, and biological effects in the offspring. The review aimed to discuss the pro-VA carotenoids and VA-associated pathways and summarize the results with reference to gestational disorders, and VA and pro-VA carotenoids as preventive agents. Also, considering that obesity, overweight, and metabolic diseases are major public health concerns worldwide, fetal and neonatal development is discussed, highlighting the physiological role of these molecules in obesity prevention. This review comprehensively summarizes the current data and shows the potential impact of these compounds on nutritional status in pregnancy and lactation.


Assuntos
Carotenoides/metabolismo , Fenômenos Fisiológicos da Nutrição do Lactente , Fenômenos Fisiológicos da Nutrição Materna , Redes e Vias Metabólicas , Vitamina A/metabolismo , Animais , Aleitamento Materno , Carotenoides/farmacologia , Dieta , Feminino , Feto/metabolismo , Humanos , Lactente , Recém-Nascido , Lactação , Estado Nutricional , Obesidade/etiologia , Obesidade/metabolismo , Gravidez , Vitamina A/farmacologia , Vitamina A/fisiologia , Deficiência de Vitamina A
16.
J Cell Biochem ; 122(1): 29-42, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32951264

RESUMO

Saffron (Crocus sativus L) is a well-known spice with active pharmacologic components including crocin, crocetin, safranal, and picrocrocin. Similar to crocin/crocetin, mesenchymal stem cells (MSCs) have been shown to display immunomodulatory and antioxidant properties, which could be beneficial in treatment of various diseases. In the current study, we have evaluated the effects of crocin and crocetin on the functions of MSCs. We used the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay to evaluate MSCs proliferation, and flow cytometry assay to measure the percentage of apoptotic MSCs and Tregs populations. Furthermore, we used the real-time polymerase chain reaction method to quantify messenger RNA (mRNA) expression of inflammatory and anti-inflammatory cytokines. Antioxidant assay was employed to quantify antioxidant parameters including nitric oxide and malondialdehyde levels besides superoxide dismutase activity. Our findings indicated that both crocin and crocetin at low concentrations (2.5 and 5 µM) exhibited significant effects on increasing MSCs viability and on protecting them against apoptosis-induced death. Furthermore, crocin and crocetin at low concentrations (2.5 and 5 µM) displayed a better antioxidant function. Moreover, increased Treg population was observed at lower doses. In addition, crocin/crocetin at low concentrations caused an elevation in mRNA expression of anti-inflammatory cytokines (transforming growth factor-ß, interleukin-10 [IL-10], and IL-4), while at higher doses (25 and 50 µM) they led to lowering inflammatory cytokines (IL-1ß, IL-6, IL-17, and interferon gamma). Altogether, both crocin and crocetin at lower concentrations exhibited more efficacies on MSCs with a better effect toward crocin. It seems that crocin and crocetin may be considered as complementary treatments for the patients who undergo MSCs transplantation.


Assuntos
Antioxidantes/farmacologia , Carotenoides/farmacologia , Células-Tronco Mesenquimais/patologia , Esclerose Múltipla/patologia , Óxido Nítrico/metabolismo , Extratos Vegetais/farmacologia , Vitamina A/análogos & derivados , Apoptose , Proliferação de Células , Células Cultivadas , Crocus/química , Humanos , Imunomodulação , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/metabolismo , Vitamina A/farmacologia
17.
J Acad Nutr Diet ; 121(1): 92-104, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33350944

RESUMO

BACKGROUND: Uterine leiomyomata (UL) are the leading indication for hysterectomy in the United States. Dietary supplementation with lycopene was associated with reduced size and incidence of oviduct leiomyoma in the Japanese quail. Two US prospective cohort studies of women reported little association between intake of lycopene, or other carotenoids, and UL incidence. However, these studies relied on self-reported physician-diagnosed UL, which is prone to misclassification. OBJECTIVE: This study examines the association between dietary intake of carotenoids and UL incidence. DESIGN: Data were derived from the Study of the Environment, Lifestyle, and Fibroids, a prospective cohort study. Women completed self-administered baseline questionnaires on demographic characteristics, reproductive history, and lifestyle, including a 110-item validated food frequency questionnaire, from which dietary intakes of carotenoids-including alpha carotene, beta carotene, cryptoxanthin, lutein-zeaxanthin, and lycopene-and vitamin A were estimated. PARTICIPANTS/SETTING: One thousand two hundred thirty Black women aged 23 to 35 years who did not have a previous diagnosis of UL, cancer, or autoimmune disease were eligible for enrollment (2010-2012). Participants were residents of the Detroit, MI, metropolitan area. MAIN OUTCOME MEASURES: Transvaginal ultrasound was used to assess UL at baseline and 20, 40, and 60 months of follow-up. STATISTICAL ANALYSES PERFORMED: Cox regression was used to estimate hazard ratios and 95% CIs, adjusted for energy intake, age at menarche, education, body mass index, parity, age at first birth, years since last birth, current use of oral contraceptives or progestin-only injectables, alcohol intake, and cigarette smoking. RESULTS: Among 1,230 women without prevalent UL at baseline, 301 incident UL cases during follow-up were identified. Intakes of lycopene, other carotenoids, and vitamin A were not appreciably associated with UL incidence. Hazard ratios comparing quartiles 2 (2,376 to 3,397 µg/day), 3 (3,398 to 4,817 µg/day), and 4 (≥4,818 µg/day) with quartile 1 (<2,376 µg/day) of lycopene intake were 1.03 (95% CI 0.72 to 1.47), 1.22 (95% CI 0.86 to 1.72), and 0.95 (95% CI 0.67 to 1.36), respectively. CONCLUSIONS: Study findings do not support the hypothesis that greater carotenoid intake is associated with reduced UL incidence.


Assuntos
Carotenoides/farmacologia , Leiomioma/tratamento farmacológico , Licopeno/farmacologia , Neoplasias Uterinas/tratamento farmacológico , Vitamina A/farmacologia , Adulto , Afro-Americanos , Estudos de Coortes , Dieta/estatística & dados numéricos , Ingestão de Alimentos , Ingestão de Energia , Feminino , Humanos , Incidência , Leiomioma/diagnóstico por imagem , Leiomioma/epidemiologia , Michigan/epidemiologia , Estudos Prospectivos , Ultrassonografia , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/epidemiologia
18.
Med Hypotheses ; 144: 110250, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33254555

RESUMO

This study presents two new concepts and definitions to the medical literature. One of those is "endogenous retinoic acid theory" and the other "retinoic acid depletion syndrome". A new classification will be provided for the immune system: "retinoic acid-dependent component" and "retinoic acid non-dependent component". If this theory is verified, all the diseases where the retinoic acid metabolism is defective and retinoic acid levels are low will be identified and new approaches will be developed fortreating such diseases. When the need for retinoic acids increases, such as acute infection, high fever, severe catabolic process, or chronic antigenic stimulation, cytochrome oxidase enzymes are inhibited by drugs or internal mechanisms. Metabolism and excretion of retinoic acids stored in the liver are prevented. In this way, retinoic acid levels in the blood are raised to therapeutic levels. This is called "Endogenous Retinoic Acid Theory". Retinoic acids also manage their metabolism through feedback mechanisms. Despite compensatory mechanisms, causes such as high fever, serious catabolic process and excessively large viral genome (SARS-CoV-2), excessive use of RIG-I and Type I interferon synthesis pathway using retinoic acid causes emptying of retinoic acid stores. As a result, the RIG-I pathway becomes ineffective, Type I IFN synthesis stops, and the congenital immune system collapses. Then the immune mechanism passes to TLR3, TLR7, TLR8, TLR9, MDA5 and UPS pathways in the monocyte, macrophage, neutrophil and dendritic cells of the adaptive immune defense system that do not require retinoic acid. This leads to excessive TNFα and cytokine discharge from the pathway. With the depletion of retinoic acid stores as a result of this overuse, the immune defense mechanism switches from the congenital immune system to the adaptive immune system, where retinoic acids cannot be used. As a result of this depletion of retinoic acids, the shift of the immune system to the NFκB arm, which causes excessive cytokine release, is called "retinoic acid depletion syndrome". COVID-19 and previously defined sepsis, SIRS and ARDS are each retinoic acid depletion syndrome. We claim that retinoic acid metabolism is defective in most inflammatory diseases, particularly COVID-19 (cytokine storm) sepsis, SIRS and ARDS. Finding a solution to this mechanism will bring a new perspective and treatment approach to such diseases.


Assuntos
COVID-19/imunologia , COVID-19/terapia , Tretinoína/metabolismo , Autoimunidade , COVID-19/metabolismo , Carotenoides/metabolismo , Proteína DEAD-box 58/imunologia , Humanos , Sistema Imunitário , Interferon Tipo I/metabolismo , Interferons/metabolismo , Fígado/metabolismo , Modelos Teóricos , Sistema Nervoso/metabolismo , Síndrome , Carga Viral , Vitamina A/farmacologia , Deficiência de Vitamina A/metabolismo , Zinco/metabolismo
19.
Nutrients ; 12(11)2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233594

RESUMO

Carotenoids may strengthen the association of antioxidant vitamins A, C, and E with favorable cognitive outcomes over time, though a few prospective studies have examined this hypothesis. We evaluated the longitudinal data from 1251 participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (Age at visit 1 in 2004-2009 (v1): 30-65 years). Vitamins A, C, and E dietary intakes and total and individual dietary carotenoids were computed using two 24-h recalls at v1. Cognitive tests, covering global mental status and domains of memory/learning, attention, psychomotor speed, visuo-spatial, language/verbal, and executive function were conducted at v1 and/or v2 (2009-2013); mean ± SD follow-up: 4.66 ± 0.93 years. Mixed-effects linear regression models detected an interaction between vitamin E and total (and individual) carotenoids for three of 11 cognitive tests at v1, with only one meeting the statistical significance upon multiple testing correction whereby vitamin E was linked with greater verbal memory performance in the uppermost total carotenoid tertile (γ0a = +0.26 ± 0.08, p = 0.002), a synergism largely driven by carotenoid lycopene. Vitamins A and C showed no consistent interactions with carotenoids. In conclusion, we provide partial evidence for synergism between vitamin E and carotenoids in relation to better baseline cognitive performance, pending further studies with time-dependent exposures and randomized trials directly examining this synergism.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Carotenoides/farmacologia , Cognição/efeitos dos fármacos , Vitamina A/farmacologia , Vitamina E/farmacologia , Adulto , Idoso , Atenção , Estudos de Coortes , Dieta , Função Executiva , Feminino , Envelhecimento Saudável , Humanos , Aprendizagem , Estilo de Vida , Masculino , Memória , Rememoração Mental , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , População Urbana
20.
Mol Med Rep ; 22(6): 5271-5281, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33173984

RESUMO

Arsenic trioxide (ATO) is commonly used to treat patients with acute promyelocytic leukemia since it was authorized by the U.S. Food and Drug Administration in the 1970s, but its applicability has been limited by its cardiotoxic effects. Therefore, the aim of the present study was to investigate the cardioprotective effects and underlying mechanism of crocetin (CRT), the critical ingredient of saffron. Sprague­Dawley rats were then randomly divided into four groups (n=10/group): i) Control group; ii) ATO group, iii) CRT­low (20 mg/kg) group; and iv) CRT­high (40 mg/kg) group. Rats in the Control and ATO groups were intraperitoneally injected with equal volumes of 0.9% sodium chloride solution, and CRT groups were administered with either 20 and 40 mg/kg CRT. Following 6 h, all groups except the Control group were intraperitoneally injected with 5 mg/kg ATO over 10 days. Cardiotoxicity was indicated by changes in electrocardiographic (ECG) patterns, morphology and marker enzymes. Histomorphological changes in the heart tissue were observed by pathological staining. The levels of superoxide dismutase, glutathione peroxidase, malondialdehyde and catalase in the serum were analyzed using colometric commercial assay kits, and the levels of reactive oxygen species in the heart tissue were detected using the fluorescent probe dihydroethidium. The expression levels of inflammatory factors and activities of apoptosis­related proteins were analyzed using immunohistochemistry. The protein expression levels of silent information regulator of transcription 1 were measured using western blotting. Cardiotoxicity was induced in male Sprague­Dawley rats with ATO (5 mg/kg). CRT (20 and 40 mg/kg) and ATO were co­administered to evaluate possible cardioprotective effects. CRT significantly reduced the heart rate and J­point elevation induced by ATO in rats. Histological changes were evaluated via hematoxylin and eosin staining. CRT decreased the levels of creatine kinase and lactate dehydrogenase, increased the activities of superoxide dismutase, glutathione­peroxidase and catalase, and decreased the levels of malondialdehyde and reactive oxygen species. Moreover, CRT downregulated the expression levels of the pro­inflammatory factors IL­1, TNF­α, IL­6, Bax and p65, as well as increased the expression of Bcl­2. It was also identified that CRT enhanced silent information regulator of transcription 1 protein expression. Thus, the present study demonstrated that CRT treatment effectively ameliorated ATO­induced cardiotoxicity. The protective effects of CRT can be attributed to the inhibition of oxidative stress, inflammation and apoptosis. Therefore, CRT represents a promising therapeutic method for improving the cardiotoxic side effects caused by ATO treatment, and additional clinical applications are possible, but warrant further investigation.


Assuntos
Intoxicação por Arsênico/tratamento farmacológico , Trióxido de Arsênio/toxicidade , Carotenoides/farmacologia , Vitamina A/análogos & derivados , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Trióxido de Arsênio/efeitos adversos , Trióxido de Arsênio/farmacologia , Cardiotônicos/farmacologia , Cardiotoxicidade/tratamento farmacológico , Carotenoides/metabolismo , China , Coração/efeitos dos fármacos , Inflamação/patologia , Masculino , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Vitamina A/metabolismo , Vitamina A/farmacologia
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