RESUMO
Albumin polymeric Nanoparticles (NPs) have opened a great expectancy as for controlled drug delivery due to their therapeutic potency. Concomitantly biodegradable NPs technologies with target linked structures to pave the way of personalised medicine are becoming increasingly important in sight of a therapeutically effective research technology. This is particularly attractive for nanoparticle-based cancer delivery systems, based on the known limitations and efforts to overcome. This new group of gamma irradiated-NPs inherited both the protein delivery properties and robustness of polymer forming structures, and gamma irradiation techniques that leave clean, innocuous and biodegradable NPs. These protein NPs made of serum albumin are referred to SA NPs that possesses several characteristics making them especially attractive to be considered as a drug delivery system. This review focused on methodologies actually being used in the synthesis and characterisation of albumin NPs and different author's opinions on strategic ways to treat cancerous cell-lines with NPs. Utterly, challenges being overthrown by researchers are brought up to anneal an effective, all in one targeted albumin NPs to passed through in vitro and preclinical trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Portadores de Fármacos/administração & dosagem , Raios gama , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Albumina Sérica/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos da radiação , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/efeitos da radiação , Raios gama/uso terapêutico , Humanos , Nanopartículas/química , Nanopartículas/efeitos da radiação , Neoplasias/metabolismo , Albumina Sérica/química , Albumina Sérica/efeitos da radiaçãoRESUMO
Human serum albumin (HSA) is the most abundant protein in the circulatory system. Oxidized albumin was identified in the skin of patients suffering from vitiligo, a depigmentation disorder in which the protection against ultraviolet (UV) radiation fails because of the lack of melanin. Oxidized pterins, efficient photosensitizers under UV-A irradiation, accumulate in the skin affected by vitiligo. In this work, we have investigated the ability of pterin (Ptr), the parent compound of oxidized pterins, to induce structural and chemical changes in HSA under UV-A irradiation. Our results showed that Ptr is able to photoinduce oxidation of the protein in at least two amino acid residues: tryptophan (Trp) and tyrosine (Tyr). HSA undergoes oligomerization, yielding protein structures whose molecular weight increases with irradiation time. The protein cross-linking, due to the formation of dimers of Tyr, does not significantly affect the secondary and tertiary structures of HSA. Trp is consumed in the photosensitized process, and N-formylkynurenine was identified as one of its oxidation products. The photosensitization of HSA takes place via a purely dynamic process, which involves the triplet excited state of Ptr. The results presented in this work suggest that protein photodamage mediated by endogenous photosensitizers can significantly contribute to the harmful effects of UV-A radiation on the human skin.
Assuntos
Albumina Sérica/química , Albumina Sérica/efeitos da radiação , Reagentes de Ligações Cruzadas , Humanos , Modelos Químicos , Oxirredução , Processos Fotoquímicos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Pterinas/química , Pterinas/efeitos da radiação , Albumina Sérica/metabolismo , Pele/metabolismo , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos da radiação , Triptofano/química , Triptofano/efeitos da radiação , Tirosina/química , Tirosina/efeitos da radiação , Raios Ultravioleta/efeitos adversosRESUMO
INTRODUCCION: La electricidad y las comunicaciones son aspectos sin los cuales es imposible la vida moderna; sin embargo, las radiaciones electromagnéticas (radiaciones no ionizantes) afectan la salud. De ahí que reviste gran importancia conocer la posible influencia que sobre el estatus oxidativo, la capacidad antioxidante y los niveles hemoquímicos pudiera ejercer la exposición a las ondas electromagnéticas no ionizantes. OBJETIVO: Valorar el comportamiento del ácido úrico, la albúmina y las proteínas totales en sujetos expuestos a las radiaciones electromagnéticas. MÉTODOS: Se realizó un estudio prospectivo, longitudinal y analítico de casos y controles en 125 sujetos del sexo masculino, con edades comprendidas entre 20 y 29 años. Se conformaron dos grupos de estudios: el primero formado por n = 63 sujetos expuestos (operan equipos de radiolocalización a través de radares) y el segundo grupo control formado por sujetos no expuestos a radiaciones ionizantes, n = 62. Para detectar diferencias significativas entre grupos fue utilizado el test T para muestras independientes. El nivel de significación fue de p ú 0,05. RESULTADOS: Al comparar ambos grupos, se observaron diferencias significativas en cuanto a los valores de proteínas totales y albúmina; sin embargo, los niveles de ácido úrico no sufrieron afectación. CONCLUSIONES: Los sujetos expuestos a radiaciones electromagnéticas no ionizantes en el orden de las supra altas frecuencias (SAF - 3 a 30 GHz) presentan un aumento significativo en los niveles de proteínas totales y de albúmina, lo cual pudiera afectar su capacidad de defensa antioxidante
INTRODUCTION: The electricity and communications are features essential in the modern life; however, the electromagnetic radiations (non-ionizing radiations affect the health. Hence, it is very important to know the potential influence that on the oxidative status, the antioxidant ability and the hemochemical levels could exert the exposition to non-ionizing electromagnetic radiations. OBJECTIVE: To assess the behavior of uric acid, the albumin and the total proteins in subjects exposed to electromagnetic radiations. METHODS: A analytical, longitudinal and prospective cases-controls study was conducted in 125 male subjects aged between 20 and 29. Two study groups were created: the first one included n= 63 exposed subjects (using radio location equipments by radar) and the second one included subjects non-exposed to ionizing radiations, n = 62. To detect significant differences among groups T test was used for independent samples. The significance level was of p ? 0,05. RESULTS: Comparing both groups it was possible to observe significant differences as regards total proteins and albumin values; however, the uric acid levels remained without affection. CONCLUSIONS: The subjects exposed to non0ionizing electromagnetic radiations in the order of very high frequencies (SAF - 3 to 30 GHz) had a significant increase in the total proteins and albumin levels, which could to affect its ability of antioxidant defense
Assuntos
Humanos , Masculino , Adulto , Ácido Úrico/efeitos da radiação , Albumina Sérica/efeitos da radiação , Proteínas Sanguíneas/efeitos da radiação , Estudos Longitudinais , Estudos ProspectivosRESUMO
Aceclofenac (Airtal) (1) is a photoallergic and phototoxic anti-inflammatory and analgesic agent. This drug is photolabile under aerobic and anaerobic conditions. Irradiation of an ethanol-solution of aceclofenac under oxygen or argon at 290-320 nm affords via decarboxlation compound 2 as the main isolated and spectroscopically identified photoproduct, besides hydroxylamine derivates 3 and 4. A radical intermediate was evidenced spectrophotometrically with GSH and DTNB, as well as by the dimerization of cysteine. Red blood cell lysis photosensitized by 1-4 was investigated. Furthermore, in a lipid-photoperoxidation test with linoleic acid the in vitro phototoxicity of aceclofenac was also verified. The photoinduced generation of peroxide by compound 1 was determined during the irradiation in presence of NADPH by chemiluminescence. In relation to the photoallergic activity of this drug, the interaction of aceclofenac with human serum albumin (HSA) has been studied through fluorescence spectroscopy. No photoinduced binding was observed after irradiation of compounds 1 in the presence of human serum albumin.
Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/toxicidade , Dermatite Fototóxica/patologia , Diclofenaco/análogos & derivados , Cisteína/efeitos dos fármacos , Cisteína/efeitos da radiação , Diclofenaco/química , Diclofenaco/toxicidade , Eritrócitos/efeitos da radiação , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Glutationa/efeitos da radiação , Hemólise/efeitos dos fármacos , Hemólise/efeitos da radiação , Humanos , Técnicas In Vitro , Ácido Linoleico/efeitos da radiação , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Luminescência , Oxidantes/química , Oxirredução , Oxigênio/sangue , Fotólise , Albumina Sérica/química , Albumina Sérica/efeitos da radiação , Raios UltravioletaRESUMO
A comparative study of the photosensitizing activity of advanced glycation endproducts (AGEs) prepared by incubating glucose (Glc), threose (Threo) and ascorbate (AH-) in the presence of lysine (Lys) was performed. Photochemical activity was evaluated under low oxygen pressure with the aim to simulate the conditions of the eye lens. AGE-sensitized tryptophan and AH- photodecomposition and glucose 6-phosphate dehydrogenase inactivation were studied. In all systems, glucose-derived AGEs showed the highest photosensitizing efficiency, followed by ascorbate and threose. The presence of different sensitizers in glycation products mixtures was investigated. For this purpose, Trp decomposition quantum yields were determined at 344 and 367 nm. The values obtained at 344 nm are between three and six times higher than those observed at 367 nm, confirming the presence of at least two compounds with different photosensitizing activities in the mixtures. The chemiluminescence associated with the AGE-mediated oxidation of free Trp and Trp residues in human serum albumin was also studied, and a good correlation between the emission of light and the extent of Trp decomposition was found. In conclusion, it is demonstrated that glucose derived AGEs, which can be formed in vivo in the eye lens of diabetic patients and are accumulated in elderly lenses, have a higher photosensitizing efficiency, at low oxygen pressure, than those arising from ascorbate and threose. This high efficiency is especially significant when proteins are employed as photochemical targets, indicating that protein-sensitizer interaction and the local environment around the sensitizers play an important role.
Assuntos
Ácido Ascórbico/efeitos da radiação , Glucosefosfato Desidrogenase/efeitos da radiação , Produtos Finais de Glicação Avançada/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Albumina Sérica/efeitos da radiação , Triptofano/efeitos da radiação , Humanos , Cristalino , Modelos Biológicos , Oxigênio , Raios UltravioletaRESUMO
The phototoxic anti-cancer drug flutamide is photolabile under UV-B light in either aerobic or anaerobic conditions. Irradiation of a methanol solution of this drug produces several photoproducts, one by photoreduction of the nitro group, one by rupture of the aromatic-NO2 bond of the parent compound, two as a result of the rupture of the CO-NH bond and one derived from the photoreduction product by scission of the aromatic-NH2 bond. Flutamide shows a photohemolytic effect on human erythrocytes and photoinduces lipid peroxidation. Studies on peripheral blood polymorphonuclear cells (neutrophils) demonstrated the phototoxicity of flutamide as well as inhibition of the cytotoxicity respiratory burst by the photoproduct derived from its photoreduction. The results suggest that the inhibition of the respiratory burst observed in phorbol myristate acetate (PMA)-activated cells is mediated by photosensitization and concomitant singlet oxygen production and/or formation of toxic photoproducts.
Assuntos
Antineoplásicos Hormonais/efeitos da radiação , Antineoplásicos Hormonais/toxicidade , Flutamida/efeitos da radiação , Flutamida/toxicidade , Antineoplásicos Hormonais/química , Flutamida/química , Hemólise/efeitos dos fármacos , Hemólise/efeitos da radiação , Humanos , Técnicas In Vitro , Peroxidação de Lipídeos/efeitos da radiação , Medições Luminescentes , Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos da radiação , Fotobiologia , Fotoquímica , Fotólise , Albumina Sérica/efeitos da radiação , Raios UltravioletaRESUMO
Estudaram-se os efeitos da irradiaçäo sobre o estado nutricional e o metabolismo energético do hospedeiro. Utilizaram-se 48 ratos adultos machos Wistar, mantidos em gaiolas metabólicas, e divididos em grupos controle (C) e irradiado (R). No período 1, pré-irradiaçäo, os ratos foram submetidos a calorimetria indireta no dia 4 (calorimetria 1) que forneceu as variáveis gasto energético (GE), quociente respiratório (QR), substrato total oxidado (STO) e proteínas (PO), glicides (GO) e lípides oxidadas (LO). A seguir transcorreu o período 2, de irradiaçäo, quando os ratos R receberam 300 cGy/ diários de irradiaçäo abdominal, por cinco dias, sob restriçäo em molde acrílico. Cada rato do grupo C passou a receber alimentaçäo pareada e foi submetido a irradiaçäo simulada. Calorimetrias foram realizadas durante esse período (II e III) e após o seu final (IV). No sacrifício (dia 14), dosou-se hemoglobina, hermatócrito, albumina e transferrina. A análise estatística dos resultados foi feita com significância de 0,05 e 0,01. No período 1, näo houve diferenças entre os grupos em relaçäo às variáveis analisadas. No período 2 ocorreu reduçäo da ingestäo de dieta e perda percentual de peso corpóreo nos dois grupos. Apesar da ingestäo semelhante, a reduçäo ponderal foi maior no grupo R que no C. A incorporaçäo de nitrogênio decresceu significantemente no período 2. Apenas a média de albumina sérica apresentou-se menor no grupo R. O QR reduziu-se na avaliaçäo calorimétrica III, mantendo-se mais baixo em IV no grupo R, sem retornar aos níveis iniciais. Houve reduçäo significante do GE apenas no grupo R, em III. No grupo R o STO diminuiu com a irradiaçäo. Em ambos houve reduçäo da PO e GO, que no grupo R se manteve reduzida em IV, mantendo menor PO. Nas condiçöes do presente estudo, a irradiaçäo abdominal determinaou reduçäo de ingestäo alimentar, perda ponderal corporal, hipoalbuminemia, reduçäo de incorporaçäo de nitrogênio e promoveu queda do gasto energético e do quociente respiratório, levando ainda a uma alteraçäo do perfil de consumo de substratos. Conclui-se que a irradiaçäo pode conduzir a desnutriçäo protéico-calórico, näo decorrente exclusivamente da anorexia a ela associada
Assuntos
Humanos , Masculino , Animais , Ratos , Metabolismo Energético/efeitos da radiação , Estado Nutricional/efeitos da radiação , Albumina Sérica/efeitos da radiação , Análise de Variância , Peso Corporal/efeitos da radiação , Calorimetria Indireta , Dieta , Ratos Wistar , Estudos de Amostragem , Transferrina/efeitos da radiaçãoRESUMO
In this study the effects on nutritional status and energetic metabolism due to abdominal irradiation were analysed. Adult male Wistar rats (48), were divided in two groups Control (C) and Radiated (R). The rats were maintained all time in metabolic cages. The study was done in two periods: Period 1 begun at 0 day, where rats adapted to cages and oral diet, had food and water "ad libitum". At the day 4 indirect calorimetric measurements were performed (calorimetry I). At Period 2, group R rats abdominal radiation at a 300cGy/day rate, for 5 consecutive days, and group C started a pair feeding process linked individually to R rats and suffered application of simulated-radiation. Two other calorimetric measurements (II,III) were performed during Period 2. After radiation the last calorimetry was performed (IV). At sacrifice (day 14) blood was collected for determination of hemoglobin, haematocrit, albumin and transferrin. There were no statistical differences among groups C and R during Period 1 (p < 0.05). Great reduction in food intake and weight variation were found in Period 2, but weight loss was significantly higher in R rats. Nitrogen balance decreased in Period 2, but without difference among the groups (p < 0.05). Serum albumin was significantly lower in R rats. Respiratory quotient decreased in both groups during Period 2, but R rats kept it lower (p < 0.05). The energy expenditure level decreased after radiation in Group R. During Period 2 total substrate oxidation decreased in R rats. Radiation decreased glucose and protein oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)