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1.
AAPS PharmSciTech ; 20(8): 319, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641892

RESUMO

Colorectal cancer has become the third most frequent reason of cancer death in men and women. Currently, natural compounds are being looked up to, for subversion and deterrence of cancers. Inositol hexaphosphate (IP6) is one such naturally occurring phosphorylated carbohydrate present in most legumes and cereals which acts as a potential antineoplastic agent and can be used effectively to prevent and treat colon carcinomas. Despite the immense potential, due to the prevalence of high charge and ability to form salts and chelates with various divalent metals, it gets excreted out quickly from the body. On reaching the colon in its original form, it can serve as an effective anticancer agent. Therefore, a suitable dosage form that can prevent the drugs from being absorbed from the upper gastrointestinal tract is required to be prepared, to target it to the colon. Thus, microspheres of IP6 using a biodegradable polymer that degrades in the colon were attempted using the solvent evaporation method. The formulation was investigated for percentage yield, encapsulation efficiency, particle size distribution modification, and release rate. Optimized formulation showed particle size of 92 ± 0.76 µm, entrapment efficiency of 67.26% ± 0.75, percent drug loading of 15.74%, and in vitro drug release 82.36 ± 0.51. The results of the in vivo study divulged that IP6 loaded pectin microspheres showed significant positive modulation of biomarker levels and restoration of colonic architecture to almost normal as observed through histopathology and scanning electron microscopy studies in DMH-induced colon tumors in Albino Wistar rats.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Ácido Fítico/química , Animais , Biomarcadores , Neoplasias do Colo/patologia , Liberação Controlada de Fármacos , Feminino , Humanos , Masculino , Microesferas , Tamanho da Partícula , Ácido Fítico/uso terapêutico , Ratos , Ratos Wistar
2.
Melanoma Res ; 29(3): 322-324, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30615010

RESUMO

Inositol hexaphosphate (IP6) also called phytic acid is a polyphosphorylated carbohydrate naturally found in cereals, nuts, grains, and high-fiber-containing foods. It has been shown to inhibit the growth of many different tumor cell lines both in vitro and in vivo like colon, pancreas, liver, prostate, and even melanoma. Vitamin B inositol is a precursor of IP6 and another naturally occurring compound with anticancer properties. We present a case report of a patient with metastatic melanoma who declined traditional therapy and opted to try over the counter supplement IP6+inositol instead. To our surprise, the patient achieved a complete remission and remains in remission 3 years later. On the basis of this case and previous preclinical studies, we believe further research is indicated in exploring antiproliferative and potential immune stimulating effects of IP6+inositol in patients with metastatic melanoma.


Assuntos
Inositol/uso terapêutico , Melanoma/tratamento farmacológico , Ácido Fítico/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Complexo Vitamínico B/uso terapêutico , Quimioterapia Combinada , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Indução de Remissão , Neoplasias Cutâneas/patologia
3.
Int J Oncol ; 53(4): 1625-1632, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30066850

RESUMO

Inositol hexaphosphate (IP6), also known as phytic acid, has been shown to exhibit anticancer effects in a number of preclinical tumor models. IP6 decreases proliferation by arresting cells in the G0/G1 phase, inhibits iron-mediated oxidative reactions, enhances differentiation and stimulates apoptosis. The present study attempted to characterize the effect of IP6 on the migration and adhesion of colon cancer SW620 cells. IP6 was assessed at concentrations of 0.2 and 1 mM during 12, 24 and 48 h of exposure. Migration ability was measured with the real-time xCELLigence Real-Time Cell Analyzer Dual Purpose system. The expression of mRNA and proteins involved in migration and cancer progression [epithelial cell adhesion molecule, intercellular adhesion molecule-1, ß-catenin, N-cadherin, E-cadherin, matrix metalloproteinase (MMP)-2 and MMP-9] was determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The changes in the expression and subcellular localization of E-cadherin were determined by indirect immunofluorescence. IP6 induced a decrease in the migration ability of the tested SW620 cell line. IP6-treated cells also showed decreased expression of N-cadherin, increased levels of E-cadherin and decreased expression of MMP-2 and MMP-9. These results indicated that IP6 has potential to modulate the migration ability and expression of markers associated with invasion in SW620 cells; however, further analysis is necessary to obtain a detailed understanding of the mechanism of action.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Ácido Fítico/farmacologia , Antineoplásicos/uso terapêutico , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Progressão da Doença , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Invasividade Neoplásica/prevenção & controle , Ácido Fítico/uso terapêutico
4.
Molecules ; 22(10)2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-28972559

RESUMO

Abstract: AKT, a serine/threonine protein kinase and mammalian target of rapamycin (mTOR) plays a critical role in the proliferation and resistance to apoptosis that are essential to the development and progression of colon cancer. Therefore, AKT/mTOR signaling pathway has been recognized as an attractive target for anticancer therapy. Inositol hexaphosphate (InsP6), a natural occurring phytochemical, has been shown to have both preventive and therapeutic effects against various cancers, however, its exact molecular mechanisms of action are not fully understood. The aim of the in vitro study was to investigate the anticancer activity of InsP6 on colon cancer with the focus on inhibiting the AKT1 kinase and p70S6K1 as mTOR effector, in relation to proliferation and apoptosis of cells. The colon cancer Caco-2 cells were cultured using standard techniques and exposed to InsP6 at different concentrations (1 mM, 2.5 mM and 5 mM). Cellular proliferative activity was monitored by 5-bromo-2'-deoxyuridine (BrdU) incorporation into cellular DNA. Flow cytometric analysis was performed for cell cycle progression and apoptosis studies. Real-time RT-qPCR was used to validate mRNA levels of CDNK1A, CDNK1B, CASP3, CASP9, AKT1 and S6K1 genes. The concentration of p21 protein as well as the activities of caspase 3, AKT1 and p70S6K1 were determined by the ELISA method. The results revealed that IP6 inhibited proliferation and stimulated apoptosis of colon cancer cells. This effect was mediated by an increase in the expression of genes encoding p21, p27, caspase 3, caspase 9 as well a decrease in transcription of AKT1 and S6K1. InsP6 suppressed phosphorylation of AKT1 and p70S6K1, downstream effector of mTOR. Based on these studies it may be concluded that InsP6 can reduce proliferation and induce apoptosis through inhibition of the AKT/mTOR pathway and mTOR effector followed by modulation of the expression and activity of several key components of these pathways in colon cancer cells.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Ácido Fítico/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Humanos , Ácido Fítico/química , Ácido Fítico/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
5.
Eur Rev Med Pharmacol Sci ; 21(2 Suppl): 43-50, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28724186

RESUMO

OBJECTIVE: Oral treatment with inositol hexaphosphate (InsP6) has shown to be efficient in decreasing adverse effects in patients with breast cancer under chemotherapy. This study was aimed at evaluating and comparing the efficacy of topical InsP6 in improving quality of life in women treated with anticancer drugs. PATIENTS AND METHODS: The study was a double-blind, randomized controlled trial (RCT) with allocation concealment of 20 patients in two groups, one (experimental) applied 4% topical formulation of InsP6 once a day, whereas the second one (control) a gel containing hyaluronic acid. InsP6 therapy started 6 weeks after lumpectomy. Blood tests were monitored in both groups and quality of life was assessed using standardized QLQ-C30 and QLQ-BR23. RESULTS: Patients who applied InsP6 on the breast significantly improved their quality of life and functional status reducing side effects compared to control group; moreover, after treatment, a significant difference between the two groups was observed in the white blood cells and platelets count values. CONCLUSIONS: Topical InsP6 treatment has demonstrated to be effective and safe in preventing and/or mitigating chemotherapy-induced side effects as well as the preserving quality of life in women with ductal breast cancer.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante/efeitos adversos , Ácido Fítico/administração & dosagem , Ácido Fítico/uso terapêutico , Administração Tópica , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Contagem de Plaquetas , Qualidade de Vida , Resultado do Tratamento
6.
Eur J Pharmacol ; 805: 67-74, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28315345

RESUMO

Colorectal cancer (CRC) is common worldwide, and most treatments for CRC have undesirable side effects. Many researchers have demonstrated that inositol hexaphosphate (IP6) has potent anticarcinogenic activity against CRC and no apparent toxicity to normal cells. However, the underlying mechanism is still unclear. In this study, we investigated the anticancer and anti-proliferative properties of IP6 in CRC and its possible mechanisms during this chemopreventive process. We examined the expression of genes related to the PI3K/Akt and Wnt pathways at the transcriptional and translational levels in a DMH-induced rat CRC model following IP6 administration. In addition, we also conducted cell proliferation analysis. The results demonstrated that IP6 could inhibit tumors, in terms of tumor incidence, number, weight and volume in DMH-induced rats. Additionally, Akt and c-Myc mRNA levels were significantly decreased. IP6 was also shown to downregulate Akt, pAkt, pGSK-3ß, and c-Myc protein expression and upregulate pß-catenin protein expression. Furthermore, tumor tissues from IP6-treated rats showed decreased proliferation. In conclusion, the anti-proliferative effect of IP6 may be related to crosstalk between the PI3K/Akt and Wnt pathways, revealing a potential mechanism of CRC inhibition by IP6 in our model.


Assuntos
1,2-Dimetilidrazina/farmacologia , Neoplasias Colorretais/patologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Ácido Fítico/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/tratamento farmacológico , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Masculino , Ácido Fítico/uso terapêutico , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar
7.
Nefrologia ; 37(1): 20-28, 2017.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27697413

RESUMO

Phytate, or myo-inositol 1,2,3,4,5,6-hexakis dihydrogen phosphate (InsP6), is a naturally occurring phosphorus compound that is present in many foods, mainly legumes, whole grains and nuts. Patients with chronic kidney disease (CKD) have cardiovascular disease mortality up to 30times higher than the general population. Vascular calcifications (VCs) directly contribute to overall morbidity and mortality, especially in CKD. In part, this high mortality is due to elevated levels of phosphorus in the blood. Therefore, control of dietary phosphorus is essential. Dietary phosphorus can be classified according to its structure in organic phosphorus (plant and animal) and inorganic (preservatives and additives). Plant-phosphorus (legumes and nuts), mainly associated with InsP6, is less absorbable by the human gastrointestinal tract as the bioavailability of phosphorous from plant-derived foods is very low. Recent data indicate that restriction of foods containing plant phosphates may compromise the adequate supply of nutrients that have a beneficial effect in preventing cardiovascular events, such as InsP6 or fibre found in legumes and nuts. Experimental studies in animals and observational studies in humans suggest that InsP6 can prevent lithiasis and VCs and protect from osteoporosis. In conclusion, we need prospective studies to elucidate the potential benefits and risks of phytate (InsP6) through the diet and as an intravenous drug in patients on haemodialysis.


Assuntos
Calcinose/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Hiperfosfatemia/complicações , Fosfatos/metabolismo , Fósforo na Dieta/farmacocinética , Ácido Fítico/metabolismo , Insuficiência Renal Crônica/metabolismo , Urolitíase/prevenção & controle , Animais , Antioxidantes/metabolismo , Arteriosclerose/prevenção & controle , Disponibilidade Biológica , Calcinose/etiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Cinacalcete/uso terapêutico , Estudos Transversais , Fabaceae , Humanos , Hiperfosfatemia/mortalidade , Masculino , Estrutura Molecular , Nozes , Estudos Observacionais como Assunto , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Fósforo na Dieta/administração & dosagem , Fósforo na Dieta/efeitos adversos , Ácido Fítico/farmacologia , Ácido Fítico/uso terapêutico , Estudos Prospectivos , Ratos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/dietoterapia , Urolitíase/etiologia
8.
Int J Exp Pathol ; 97(5): 397-407, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27921351

RESUMO

Inositol hexakisphosphate (IP6) and inositol both regulate insulin secretion, but their combined use in the management of diabetes deserves investigation. The combined effects of IP6 and inositol supplementation were investigated in streptozotocin-induced type 2 diabetic rats. The following groups of rats were studied for 8 weeks: non-diabetic control, non-diabetic high-fat diet control, diabetic untreated, diabetic rats treated with the combination of IP6 and inositol (650 mg/kg bw) and diabetic rats treated with glibenclamide (10 mg/kg bw). High-fat diet and streptozotocin were used to induce type 2 diabetes mellitus in Sprague-Dawley rats. Body weight, blood glucose, glycated haemoglobin, insulin, serum leptin, HOMA-insulin resistance scores, intestinal amylase activity, serum and faecal lipids and food and fluid consumption were measured. Treatment with the combination significantly reduced blood glucose (306 ± 53 mg/dl) and insulin resistance score (1.93 ± 0.45) compared with diabetic controls (522 ± 24 mg/dl and 5.1 ± 0.69 respectively). Serum leptin (2.8 ± 0.6 ng/dl) and faecal triglycerides (108 ± 8 mg/dl) were significantly increased in rats treated with the combination compared with the diabetic control (1.8 ± 0.06 ng/dl and 86 ± 4 mg/dl). Serum triglyceride (47 ± 5.1 mg/dl), total cholesterol (98 ± 3.2 mg/dl) and food intake (26 ± 0.3 g) were significantly reduced by 45%, 25% and 25%, respectively, in rats treated with the combination compared with the diabetic control. Inositol and IP6 combined supplementation may be effective in the management of type 2 diabetes mellitus and related metabolic disorders by regulating some aspects of lipid and carbohydrate metabolism.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inositol/uso terapêutico , Ácido Fítico/uso terapêutico , Amilases/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Suplementos Nutricionais , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Avaliação Pré-Clínica de Medicamentos/métodos , Quimioterapia Combinada , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Fezes/química , Hipoglicemiantes/farmacologia , Inositol/farmacologia , Intestinos/enzimologia , Leptina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Ácido Fítico/farmacologia , Ratos Sprague-Dawley
9.
Nutrients ; 8(5)2016 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-27187454

RESUMO

Inositol hexaphosphate (IP6) and inositol (Ins), naturally occurring carbohydrates present in most mammals and plants, inhibit the growth of numerous cancers both in vitro and in vivo. In this study, we first examined the anti-metastatic effects of IP6 and Ins using a liver metastasis model of colorectal cancer (CRC) in BALB/c mice. CT-26 cells were injected into the splenic capsule of 48 BALB/c mice. The mice were then randomly divided into four groups: IP6, Ins, IP6 + Ins and normal saline control (n = 12 per group). IP6 and/or Ins (80 mg/kg each, 0.2 mL/day) were injected into the gastrointestinal tracts of the mice on the second day after surgery. All mice were sacrificed after 20 days, and the tumor inhibition rates were determined. The results demonstrated that the tumor weights of liver metastases and the tumor inhibition rates were reduced in the experimental groups compared to the control group and that treatment with the combination of IP6 and Ins resulted in greater inhibition of tumor growth than treatment with either compound alone. These findings suggest that IP6 and Ins prevent the development and metastatic progression of colorectal cancer to the liver in mice by altering expression of the extracellular matrix proteins collagen IV, fibronectin and laminin; the adhesion factor receptor integrin-ß1; the proteolytic enzyme matrix metalloproteinase 9; and the angiogenic factors vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor beta in the tumor metastasis microenvironment. In conclusion, IP6 and Ins inhibited the development and metastatic progression of colorectal cancer to the liver in BALB/c mice, and the effect of their combined application was significantly greater than the effect of either compound alone. This evidence supports further testing of the combined application of IP6 and Ins for the prevention of colorectal cancer metastasis to the liver in clinical studies.


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias Colorretais/patologia , Inositol/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Ácido Fítico/uso terapêutico , Adenocarcinoma/patologia , Adenocarcinoma/prevenção & controle , Adenocarcinoma/secundário , Animais , Neoplasias Colorretais/tratamento farmacológico , Feminino , Inositol/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica/prevenção & controle , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/secundário , Ácido Fítico/administração & dosagem , Distribuição Aleatória
10.
J Cosmet Dermatol ; 15(3): 269-82, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27028014

RESUMO

BACKGROUND: Melasma is one of the most frequently diagnosed hyperpigmentation changes on the skin of women's faces. Nearly 30% of women using oral estrogen therapy struggle with this problem. A common way of reducing melasma is the application of azelaic acid products. AIM: Comparison of efficacy of three dermocosmetic products, containing azelaic acid, in the reduction in melasma for women aged 35-55. MATERIAL AND METHODS: A group of 60 women diagnosed with melasma were divided into three even, twenty-person subgroups. Each subgroup was assigned one dermocosmetic product containing azelaic acid. For 24 weeks, the patients applied the assigned product twice a day. The level of the colorant within the hyperpigmentation was marked before the treatment, after 1 month, after 3 months, and after 6 months of therapy. The pigmentation was measured using Mexameter(®) (Courage + Khazaka electronic, Germany). In addition, during each inspection, the patients' level of hydration, elasticity, and intensity of erythema was checked using Corneometer(®) , Reviscometer(®) . RESULTS: All dermocosmetics containing azelaic acid that were applied significantly contributed to the reduction in pigment in the pigmentary lesion. The largest decrease in the amount of pigment was observed in the first 3 months of use of the products. A combination containing 20% azelaic acid and mandelic acid, phytic acid, 4N-butyl resorcinol, and ferulic acid proved to be the most effective dermocosmetic III (Sesderma, Valencia, Spain). CONCLUSIONS: Dermocosmetics containing azelaic acid significantly contribute to the clearing of melasma. The effect depends on the treatment time, the acid concentration, and addition of other components.


Assuntos
Cosmecêuticos/química , Cosmecêuticos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Ácidos Dicarboxílicos/uso terapêutico , Melanose/tratamento farmacológico , Adulto , Fármacos Dermatológicos/análise , Ácidos Dicarboxílicos/análise , Combinação de Medicamentos , Feminino , Humanos , Ácidos Mandélicos/uso terapêutico , Pessoa de Meia-Idade , Ácido Fítico/uso terapêutico , Resorcinóis/uso terapêutico , Fatores de Tempo
11.
Dermatol Surg ; 42(3): 384-91, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26859648

RESUMO

BACKGROUND: Melasma is acquired symmetric hypermelanosis characterized by light-to-deep brown pigmentation over cheeks, forehead, upper lip, and nose. Treatment of this condition is difficult and associated with high recurrence rates. Chemical peels have become a popular modality in the treatment of melasma. OBJECTIVE: To compare the therapeutic efficacy and tolerability of glycolic acid (35%) versus salicylic-mandelic (SM) acid (20% salicylic/10% mandelic acid) versus phytic combination peels in Indian patients with melasma. MATERIALS AND METHODS: Ninety patients diagnosed with melasma were randomly assigned into 3 groups of 30 patients each. Group A received glycolic acid (GA-35%) peel, Group B received SM acid, and Group C received phytic combination peels. Each group was primed with 4% hydroquinone and 0.05% tretinoin cream for 4 weeks before treatment. Chemical peeling was done after every 14 days in all groups until 12 weeks. Clinical evaluation using melasma area and severity index (MASI) score and photography was recorded at every visit and follow-up was done until 20 weeks. RESULTS: There was a decrease in MASI score in all 3 groups but it was statistically significantly lower in Group A than Group C (p = .00), and it was also statistically significantly lower in Group B than Group C (p = .00) but there was no statistically significant difference between Groups A and B (p = .876). Objective response to treatment evaluated by reduction in MASI scoring after 12 weeks was 62.36% reduction in GA group, 60.98% reduction in SM group, and 44.71% in phytic acid group. CONCLUSION: It is concluded that GA (35%) and SM acid peels are both equally efficacious and a safe treatment modality for melasma in Indian skin, and are more effective than phytic acid peels. Salicylic-mandelic peels are better tolerated and more suitable for Indian skin.


Assuntos
Abrasão Química/métodos , Glicolatos/uso terapêutico , Ceratolíticos/uso terapêutico , Ácidos Mandélicos/uso terapêutico , Melanose/terapia , Ácido Fítico/uso terapêutico , Ácido Salicílico/uso terapêutico , Adulto , Antioxidantes/uso terapêutico , Combinação de Medicamentos , Feminino , Seguimentos , Glicolatos/efeitos adversos , Humanos , Hidroquinonas/uso terapêutico , Índia , Ceratolíticos/efeitos adversos , Masculino , Ácidos Mandélicos/efeitos adversos , Pessoa de Meia-Idade , Ácido Fítico/efeitos adversos , Estudos Prospectivos , Ácido Salicílico/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento , Tretinoína/uso terapêutico , Adulto Jovem
12.
Neurosci Lett ; 597: 132-6, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25929185

RESUMO

Phytic acid (PA) is a naturally occurring constituent which exhibits protective action in Parkinson's disease (PD). Inflammation in the central nervous system (CNS) is strongly associated with neuronal death in PD. However, the molecular mechanism of the protective effect of PA in PD has not been fully elucidated. In this study, we tried to testify the protection of PA on neuron and inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model of mice and investigated the mechanism involved in them. Motor behavior test and tyrosine hydroxylase (TH) immunohistochemistry method showed PA significantly inhibited MPTP-induced dopaminergic cell loss in the substantia nigra (SN). Moreover, using immunohistochemistry method and quantitative polymerase chain reaction (qPCR), microglial activation and inducible nitric oxide synthase (iNOS) were found to be markedly repressed by PA. Via western blot assay, expressions of nuclear factor κB (NF-κB) and phosphorylated extracellular signal-regulated kinase (p-ERK) were significantly attenuated by PA. In conclusion, it is suggested that PA has a neuroprotective effect in MPTP-induced PD model and the neuroprotection is correlated with its anti-inflammatory effect which may be associated with suppression of pathways that involved in NF-κB and p-ERK.


Assuntos
Anti-Inflamatórios/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Ácido Fítico/farmacologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Anti-Inflamatórios/uso terapêutico , Proteínas de Ligação ao Cálcio/metabolismo , Neurônios Dopaminérgicos/patologia , Ativação Enzimática , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Microglia/metabolismo , Destreza Motora/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Óxido Nítrico Sintase Tipo II/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Parte Compacta da Substância Negra/efeitos dos fármacos , Parte Compacta da Substância Negra/patologia , Fosforilação , Ácido Fítico/uso terapêutico
13.
Toxicol Ind Health ; 31(12): 1258-68, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23796758

RESUMO

Cadmium (Cd) is one of the most dangerous occupational and environmental toxins. The objective of the present study is to examine the potential prophylactic effects of phytic acid (PA) on thyroid hormones of male rats intoxicated with Cd. The male albino rats were divided into five groups: group I (control) was fed with the basal diet, group II was intoxicated with Cd in drinking water, groups III, IV, and V were intoxicated with Cd in drinking water and fed with the diet containing 3.5, 7, and 10 g of PA/kg, respectively. The results indicated that the serum calcium, iron (Fe), and total Fe binding capacity levels and serum T3 and T4 in Cd-treated rats of group II were decreased when compared with the control group, while PA-administered groups with Cd showed a significant improvement when compared with the Cd-treated rats only. Serum thyroid stimulating hormone (TSH) level was significantly increased in Cd-treated rats compared with the control group, while the addition of PA in diet decreased the high levels of TSH. These results indicated a prophylactic effect of PA against Cd-induced toxicity in rats.


Assuntos
Intoxicação por Cádmio/prevenção & controle , Quelantes/uso terapêutico , Suplementos Nutricionais , Ácido Fítico/uso terapêutico , Adeno-Hipófise/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Animais , Cádmio/sangue , Cádmio/química , Cádmio/metabolismo , Cádmio/toxicidade , Cloreto de Cádmio/administração & dosagem , Intoxicação por Cádmio/sangue , Intoxicação por Cádmio/metabolismo , Intoxicação por Cádmio/patologia , Quelantes/administração & dosagem , Poluentes Ambientais/antagonistas & inibidores , Poluentes Ambientais/sangue , Poluentes Ambientais/metabolismo , Poluentes Ambientais/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ácido Fítico/administração & dosagem , Adeno-Hipófise/metabolismo , Adeno-Hipófise/patologia , Distribuição Aleatória , Ratos Sprague-Dawley , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Tireotropina/agonistas , Tireotropina/antagonistas & inibidores , Tireotropina/sangue , Tireotropina/metabolismo , Tiroxina/agonistas , Tiroxina/antagonistas & inibidores , Tiroxina/sangue , Tiroxina/metabolismo , Distribuição Tecidual , Toxicocinética , Tri-Iodotironina/agonistas , Tri-Iodotironina/antagonistas & inibidores , Tri-Iodotironina/sangue , Tri-Iodotironina/metabolismo
14.
Nutr Res ; 34(12): 1085-91, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25444642

RESUMO

Dietary phytic acid (PA; myo-inositol [MI] hexaphosphate) is known to inhibit colon carcinogenesis in rodents. Dietary fiber, which is a negative risk factor of colon cancer, improves characteristics of the colonic environment, such as the content of organic acids and microflora. We hypothesized that dietary PA would improve the colonic luminal environment in rats fed a high-fat diet. To test this hypothesis, rats were fed diets containing 30% beef tallow with 2.04% sodium PA, 0.4% MI, or 1.02% sodium PA + 0.2% MI for 3 weeks. Compared with the control diet, the sodium PA diet up-regulated cecal organic acids, including acetate, propionate, and n-butyrate; this effect was especially prominent for cecal butyrate. The sodium PA + MI diet also significantly increased cecal butyrate, although this effect was less pronounced when compared with the sodium PA diet. The cecal ratio of Lactobacillales, cecal and fecal mucins (an index of intestinal barrier function), and fecal ß-glucosidase activity were higher in rats fed the sodium PA diet than in those fed the control diet. The sodium PA, MI, and sodium PA + MI diets decreased levels of serum tumor necrosis factor α, which is a proinflammatory cytokine. Another proinflammatory cytokine, serum interleukin-6, was also down-regulated by the sodium PA and sodium PA + MI diets. These data showed that PA may improve the composition of cecal organic acids, microflora, and mucins, and it may decrease the levels of serum proinflammatory cytokines in rats fed a high-fat, mineral-sufficient diet.


Assuntos
Ceco/efeitos dos fármacos , Colo/efeitos dos fármacos , Citocinas/sangue , Dieta Hiperlipídica/efeitos adversos , Dieta , Fibras na Dieta/farmacologia , Ácido Fítico/farmacologia , Acetatos/metabolismo , Animais , Ácidos e Sais Biliares , Butiratos/metabolismo , Ceco/metabolismo , Ceco/microbiologia , Colo/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/prevenção & controle , Gorduras na Dieta/efeitos adversos , Fibras na Dieta/uso terapêutico , Fezes/química , Inflamação/etiologia , Inflamação/metabolismo , Mediadores da Inflamação/sangue , Interleucina-6/sangue , Lactobacillales , Linfotoxina-alfa/sangue , Masculino , Mucinas/metabolismo , Ácido Fítico/uso terapêutico , Propionatos/metabolismo , Ratos Sprague-Dawley , beta-Glucosidase/metabolismo
15.
Asian Pac J Cancer Prev ; 14(5): 3093-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23803085

RESUMO

BACKGROUND: Phytic acid (PA) is a polyphosphorylated carbohydrate that can be found in high amounts in most cereals, legumes, nut oil, seeds and soy beans. It has been suggested to play a significant role in inhibition of colorectal cancer. This study was conducted to investigate expression changes of ß-catenin and cyclooxygenase-2 (COX-2) and cell proliferation in the adenoma-carcinoma sequence after treatment with rice bran PA by immunocytochemistry. MATERIALS AND METHODS: Seventy-two male Sprague-Dawley rats were divided into 6 equal groups with 12 rats in each group. For cancer induction two intraperitoneal injections of azoxymethane (AOM) were given at 15 mg/kg bodyweight over a 2-weeks period. During the post initiation phase, two different concentrations of PA, 0.2% (w/v) and 0.5% (w/v) were administered in the diet. RESULTS: Results of ß-catenin, COX-2 expressions and cell proliferation of Ki-67 showed a significant contribution in colonic cancer progression. For ß-catenin and COX-2 expression, there was a significant difference between groups at p<0.05. With Ki-67, there was a statistically significant lowering the proliferating index as compared to AOM alone (p<0.05). A significant positive correlation (p=0.01) was noted between COX-2 expression and proliferation. Total ß-catenin also demonstrated a significant positive linear relationship with total COX-2 (p=0.044). CONCLUSIONS: This study indicated potential value of PA extracted from rice bran in reducing colonic cancer risk in rats.


Assuntos
Adenoma/prevenção & controle , Azoximetano/toxicidade , Neoplasias do Colo/prevenção & controle , Ciclo-Oxigenase 2/química , Oryza/química , Ácido Fítico/uso terapêutico , beta Catenina/antagonistas & inibidores , Adenoma/induzido quimicamente , Adenoma/metabolismo , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Carcinógenos/toxicidade , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/metabolismo , Ciclo-Oxigenase 2/metabolismo , Técnicas Imunoenzimáticas , Masculino , Ratos , Ratos Sprague-Dawley , beta Catenina/metabolismo
16.
Urology ; 80(5): 1163.e13-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22748613

RESUMO

OBJECTIVE: To study the possible effects caused by the interaction of some urinary components on the inhibition of calcium oxalate crystallization. Such interactions are susceptible to importantly change the inhibitory behavior of some urinary components by producing either positive (synergistic) or negative effects on preventing crystallization. METHODS: A urinary lithogenic risk (ULR) test was used to follow the crystallization of calcium oxalate from artificial urine in the presence of binary mixtures of known inhibitors of its crystallization (phytate, pyrophosphate, citrate, and chondroitin sulfate), which were assayed in physiological concentrations. RESULTS: Only the mixtures phytate + pyrophosphate and phytate + citrate manifested interaction effects on the calcium oxalate crystallization. Although the former exhibited synergistic effects, the latter showed negative effects on the inhibition. These effects are explained in terms of the affinity of the inhibitors for the calcium oxalate crystals surface and their concentrations in urine. CONCLUSION: The crystallization inhibitory capacity of target urine is explained by the combined effect of the compounds present in the complex urine matrix rather than the individual action of each compound. This kind of interactions is of key value in designing prophylactic treatments of urolithiasis based on inhibitors intake.


Assuntos
Oxalato de Cálcio/química , Ácido Cítrico/uso terapêutico , Ácido Fítico/uso terapêutico , Cálculos Urinários/prevenção & controle , Oxalato de Cálcio/antagonistas & inibidores , Quelantes/uso terapêutico , Cristalização , Humanos , Cálculos Urinários/etiologia , Cálculos Urinários/urina
17.
Artigo em Inglês | MEDLINE | ID: mdl-22827714

RESUMO

The central objective in treating patients with Parkinson's disease (PD) is two-fold (i) to increase the striatal dopamine content and (ii) to prevent further degeneration of the surviving dopaminergic neurons in the substantia nigra region of the ventral midbrain. Most of the current PD drugs contribute to the former and provide symptomatic relief. Although compounds such as Levodopa (L-DOPA) improve the striatal dopamine content, their long-term usage is associated with progressive decrease in drug response, motor fluctuations, dyskinesias and drug-induced toxicity. In addition, these drugs fail to prevent the progression of the degenerative process. This has shifted the focus onto alternative therapeutic approaches involving natural products that could provide independent therapy or offer neuroprotective support to the existing drugs. The current review describes the neuroprotective and therapeutic utility of such natural products including herbal extracts, phytochemicals and bioactive ingredients from other natural sources either in isolation or in combination, with potential application in PD, highlighting the relevant patents.


Assuntos
Produtos Biológicos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Fitoterapia/métodos , Animais , Toxinas Botulínicas/uso terapêutico , Gengibre , Humanos , Levodopa/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Nicotina/uso terapêutico , Patentes como Assunto , Ácido Fítico/uso terapêutico , Piper nigrum , Extratos Vegetais/uso terapêutico
18.
Br J Haematol ; 157(3): 357-69, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22404654

RESUMO

Patients with sickle cell disease (SCD) can present several severe symptoms during their lifetime, including painful events due to vascular occlusion (VOC). Even though multiple factors are involved in VOC, hypoxia is the most important triggering factor. Inositol hexaphosphate (IHP) reduces the oxygen-haemoglobin affinity thus improving the oxygen release in the blood stream and in the tissues. Thus, IHP-loaded homologous red blood cells (IHP-RBCs) could be able to reduce disorders in SCD. The effectiveness of treatment was assessed in two types of SCD transgenic mice (BERK and SAD). The administration of four repeated injections of IHP-RBCs in BERK mice resulted in an improved survival rate and brain development, prevention of severe anaemia and a greatly lowered risk of VOC. After one injection of IHP-RBCs, SAD mice were subjected to acute hypoxic stress. Analysis of the lungs revealed significantly decreased mRNA levels of molecules involved in intravascular disorders. Our results showed that transfusion of homologous IHP-RBCs, by increasing the oxygen delivery, reduces SCD disorders in sickle transgenic mice.


Assuntos
Anemia Falciforme/terapia , Transfusão de Eritrócitos/métodos , Ácido Fítico/uso terapêutico , Anemia Falciforme/complicações , Anemia Falciforme/fisiopatologia , Animais , Arteriopatias Oclusivas/etiologia , Arteriopatias Oclusivas/prevenção & controle , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Modelos Animais de Doenças , Transfusão de Eritrócitos/efeitos adversos , Feminino , Hipóxia/etiologia , Hipóxia/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Tamanho do Órgão , Fatores de Risco , Baço/crescimento & desenvolvimento , Baço/patologia , Análise de Sobrevida , Resultado do Tratamento
19.
J Cosmet Dermatol ; 10(4): 266-72, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22151934

RESUMO

BACKGROUND: Solar lentigines (SL) are benign signs of sun damage that many people find distressing. AIM: To assess the efficacy and safety of L-ascorbic acid 10% + phytic acid 2% for treating SL. PATIENTS/METHODS: A double-blind, vehicle-controlled trial in 30 healthy subjects with ≥2 SL. Subjects were randomly assigned to apply product to one side of the body and vehicle to the other twice daily for 3 months with follow-up of 2 months. RESULTS: The pigmentation index for product-treated SL was reduced (maximum reduction 1.3 at 3 months [M3]), while that for vehicle-treated lesions remained stable. These differences were statistically significant for M1-M4 (P ≤ 0.003). Dermoscopy detected significant intergroup differences in pigmentation at M5 (P=0.011). Colorimetry results indicated a statistically significant improvement in brightness (L*) between study drug and vehicle at M5. Fifteen subjects experienced 23 adverse events; six (mostly halo depigmentation) were judged possibly related to the study drug. There were six instances of mild-to-moderate intolerance in the study drug group and five in the vehicle-treated group. CONCLUSIONS: Study treatment was significantly more efficacious than vehicle in many respects and was well tolerated. Future, larger studies are needed to confirm these results and to compare the product with gold standard treatments.


Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Lentigo/tratamento farmacológico , Ácido Fítico/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/efeitos adversos , Ácido Ascórbico/efeitos adversos , Ácido Ascórbico/sangue , Colorimetria , Dermoscopia , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Lentigo/sangue , Masculino , Pessoa de Meia-Idade , Ácido Fítico/efeitos adversos , Ácido Fítico/sangue , Estatísticas não Paramétricas
20.
Comp Med ; 61(1): 39-44, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21819680

RESUMO

UVB radiation damages keratinocytes, potentially inducing chronic skin damage, cutaneous malignancy, and suppression of the immune system. Naturally occurring agents have been considered for prevention and treatment of various kinds of cancer, including skin cancer. Inositol hexaphosphate (IP6), an antioxidant, is a naturally occurring polyphosphorylated carbohydrate that has shown a strong anticancer activity in several experimental models. We assessed the protective effects of IP6 against UVB irradiationinduced injury and photocarcinogenesis by using HaCaT cells (human immortalized keratinocytes) and SKH1 hairless mice. We found that IP6 counteracts the harmful effects of UVB irradiation and increases the viability and survival of UVB-exposed cells. Treatment with IP6 after UVB irradiation (30 mJ/cm(2)) arrested cells in the G(1) and G(2) M phases while decreasing the S phase of the cell cycle. Treatment with IP6 also decreased UVB-induced apoptosis and caspase 3 activation. Topical application of IP6 followed by exposure to UVB irradiation in SKH1 hairless mice decreased tumor incidence and multiplicity as compared with control mice. Our results suggest that IP6 protects HaCaT cells from UVB-induced apoptosis and mice from UVB-induced tumors.


Assuntos
Ácido Fítico/uso terapêutico , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular , Feminino , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Camundongos , Neoplasias Cutâneas/tratamento farmacológico
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