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1.
J Photochem Photobiol B ; 240: 112665, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36736031

RESUMO

Worldwide, the most frequently diagnosed cancer is female breast cancer, and it poses a serious global health threat. Traditional cancer therapies are associated with various side effects, so developing better therapies for breast cancer is necessary, such as laser therapy which could be a promising treatment option. The aim of the current study was to investigate the femtosecond laser irradiation effect on breast cancer using T47D cell line as an in vitro model. Cells were seeded at a density of 5 × 104 cells/well in 96-well plates and incubated overnight. After that, the cells were exposed to femtosecond laser irradiation at various wavelengths falling in the UV, visible, and IR ranges for 3, 5, or 10 min and at a constant power of 100 mW. Cell viability was measured directly and 24 h after femtosecond laser irradiation using MTT assay. When using different femtosecond laser irradiation parameters, especially the 380 and 400 nm femtosecond laser irradiation, there was significant inhibition of breast cancer cell growth, either directly or 24 h after femtosecond laser exposure. Also, 420 and 440 nm significantly affected the viability of the cells. It was also observed that increasing exposure time enhances the observed effect, so 10 min exposure time was the best time of exposure. However, 700, 720, 750, and 780 nm did not significantly affect the cells viability with different exposure times. It was possible to conclude from the aforementioned results that femtosecond laser irradiation exerted a significant anticancer effect against T47D cells. Consequently, the femtosecond laser could be used successfully for breast cancer management.


Assuntos
Neoplasias da Mama , Terapia a Laser , Terapia com Luz de Baixa Intensidade , Feminino , Humanos , Neoplasias da Mama/radioterapia , Lasers , Proliferação de Células/efeitos da radiação
2.
Ann Med Surg (Lond) ; 84: 104952, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36536726

RESUMO

Background: Obesity is a chronic condition that affects millions globally; consequently, bariatric surgery is the key to this serious issue. Bariatric procedures are rapidly expanding in number and methods to address the recognized problems. So, it would make a sense for surgeons and patients if there is a more physiological bypass surgery technique in Morbid obesity. This study aims to evaluate the outcome proposed technique. Patients and methods: The present study is a retrospective analysis on 256 participants subjected to the proposed bypass procedure from December 1999 to January 2017, the participants were followed up for an interval of 3years. Results: The findings of the present study revealed a significant Excess Weight Loss (EWL). In addition, patients experienced decreased calcium, iron, vitamin B12, Hemoglobin, zinc, and Prothrombin Concentration. However, three to six months after surgery, they experienced a significant improvement until they reached normal levels without any supplement by the end of 12,18 months, with a three-year follow-up. Conclusion: This proposed Bypass Operation aims to adequate digestions as well as selective absorption without inducing any vital deficit. Most of study's population showed no elements inadequacies, although few percentages emerged during the interval of maximal weight reduction, and it were transient and minimal. No minerals or vitamins were needed.

3.
J Complement Integr Med ; 18(4): 761-767, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33781011

RESUMO

BACKGROUND: Alzheimer's (AD) is one of the most common neurodegenerative diseases, causing dementia and brain cells death. OBJECTIVES: This study aimed to assess the ameliorating effect of Acidophilus probiotic against AD induced in rats by d-galactose and AlCl3 injection via evaluating mitochondrial parameter changes in hippocampus. METHODS: This study was carried out on rats were classified into five groups; G1 (control group), G2 (probiotic group), G3 (AD group), G4 (co-treated group) and G5 (post-treated group). By the end of the experiment, some different neurotransmitters, oxidative stress biomarkers, zinc, blood glucose, Na+K-ATPase subunit alpha 1 (ATP1A1), and gene expression of mitochondrial membrane potential (MMP) were measured. RESULTS: Significant changes in neurotransmitters, antioxidants levels and decreased ATP1A1 activity and gene expression of MMP in the hippocampus in G3 were detected if compared to control. Best improvement in G5 than G4 group was observed. These results were confirmed by histological and immunohistochemical studies in hippocampus. CONCLUSIONS: Acidophilus probiotic was able to alleviate learning and memory associated injuries in AD by reducing mitochondrial dysfunction induced by d-galactose and AlCl3. This may be associated with its antioxidant properties.


Assuntos
Doença de Alzheimer , Probióticos , Doença de Alzheimer/tratamento farmacológico , Animais , Modelos Animais de Doenças , Hipocampo/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar
4.
Environ Sci Pollut Res Int ; 28(18): 22886-22901, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33432409

RESUMO

Diabetes mellitus is considered a set of diseases that lead to high glucose level due to the absolute or relative absence of insulin. The study investigated the antioxidant activity and antidiabetic effect of phlorotannins extracted from brown seaweed Cystoseira compressa. Phlorotannins were extracted from C. compressa. It was confirmed by 2,4 dimethoxy benzaldehyde assay (DMBA), ultraviolet spectra, Fourier transform infrared spectroscopy, and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The free radical scavenging activity of phlorotannins was estimated by total antioxidant capacity, 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activity, and 2,2 azino-bis3-ethylbenthiazoline-6-sulfonic acid assays. Four groups of albino rats used in this study include control normal, control phlorotannins extract, diabetic by intraperitoneally administering of streptozotocin, and diabetic treatment with 60 mg/kg of phlorotannin extract after 4 weeks of diabetes induction. The main compound identified by UPLC-MS/MS in C. compressa extract belonged to the fuhalol. C. compressa extract showed high antioxidant properties. Phlorotannins significantly decreased serum glucose, liver malondialdehyde, and α-amylase, glucosidase activities. However, total antioxidant capacity, serum insulin, hepatic glutathione, and AMPKα2 expression in skeletal muscle were improved compared to the diabetic group. The histopathological examination showed that phlorotannins markedly reduced damage in ß cells of pancreases. Phlorotannins from C. compressa have efficient antioxidant activity and the antidiabetic effect that may be utilized in human health.


Assuntos
Diabetes Mellitus Experimental , Alga Marinha , Animais , Antioxidantes , Cromatografia Líquida , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes , Extratos Vegetais , Ratos , Estreptozocina , Espectrometria de Massas em Tandem
5.
Lasers Med Sci ; 36(3): 641-647, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32725427

RESUMO

We investigated the influence of femtosecond laser irradiation on the growth of the two most common infectious bacterial pathogens in wounds; Staphylococcus aureus and Pseudomonas aeruginosa as an attempt to validate optimum parameters for a laser-based bactericidal modality to be used clinically. Bacterial cultures were exposed to femtosecond laser irradiation at different wavelengths, exposure times, and laser powers. The source of femtosecond laser was INSPIRE HF100 laser system, Spectra-Physics, which is pumped by a mode-locked femtosecond Ti: sapphire laser MAI TAI HP, Spectra-Physics. After irradiation, bacterial cells' survival was monitored by observing the clear zones of inhibition in cultured agar plates. Results for all strains indicated that the exposure to femtosecond laser irradiation with a wavelength ranging from ultraviolet (λ > 350 nm) to blue laser light (λ < 480 nm), for a period above 20 min and with a power density of ≈ 0.063 W/cm2, was enough to inhibit both bacterial pathogens with the results maintained for 1 week following irradiation.


Assuntos
Antibacterianos/farmacologia , Lasers , Ferimentos e Lesões/microbiologia , Doença Crônica , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos da radiação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/efeitos da radiação
6.
Sci Total Environ ; 703: 134664, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31757552

RESUMO

Environmental exposure to BPA is alarming because of the potential health threats for example those concerning the thyroid glands which may show signs of oxidative stress. This original study aimed to investigate the possible antioxidant protective effects of ginger extract (GE) against BPA-induced thyroid injury in male rats, focusing on its effect on Nrf-2/HO-1 signaling and thyroid hormone synthesis regulating genes. The cascade of events in thyroid injury induced by chronic exposure to BPA (200 mg/kg b.w/day for 35 days) involved a preliminary overproduction of ROS followed by significant (p ≤ 0.05) depletion of reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity as well as significant increases of malondialdehyde (MDA) contents, myeloperoxidase (MPO) activity and inducible nitric oxide synthase (iNOS) gene expression. These actions consequently down-regulate the Nrf-2/HO-I signaling which eventually resulting in the DNA fragmentation within the thyroid tissues. Moreover, BPA administration caused a reduction of thyroid iodide uptake evidenced by significant inhibitions (p ≤ 0.05) of sodium-iodide symporter (NIS), thyroid peroxidase (TPO) and thyroid-stimulating hormone receptor (TSHR) mRNA expressions within the thyroid glands. A subsequent significant decreased serum levels of T3 and T4 accompanied by a significantly increased serum TSH level were also detected. These findings were confirmed by the severe pathological changes detected in the thyroid tissue of BPA treated rats. These biochemical and histological alterations were significantly alleviated with ginger administration (250 mg/kg b.w/day for 35 days) plus BPA. In conclusion, ginger extract is a potent antioxidant that can effectively protect against BPA-induced thyroid oxidative damage by activating the Nrf-2/HO-1 gene expressions and enhancing the thyroid hormones synthesis. This is the first study to show the contribution of Nrf-2/HO-1 pathway to the protective effect of ginger extract against BPA-induced thyroid oxidative damage and thyroid hormonal disruption.


Assuntos
Zingiber officinale , Animais , Compostos Benzidrílicos , Masculino , Estresse Oxidativo , Fenóis , Extratos Vegetais , Ratos , Hormônios Tireóideos
7.
Biomed Pharmacother ; 101: 58-73, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29477473

RESUMO

This study aimed to evaluate the effect of quercetin and the photo-stimulatory effect of low energy 632.8 nm laser irradiation on excisional wound healing in non-diabetic and diabetic rats. Streptozotocin (45 mg/kg body weight) was intraperitoneally applied for diabetes induction. A full-thickness skin wound (2 × 2 cm2) was aseptically created with a scalpel in non-diabetic and diabetic rats on the shaved back of the animals. The wounded non-diabetic and diabetic rats were treated every other day with quercetin by oral gavage at dose 25 mg/kg body weight and/or with low level laser therapy (LLLT) for 14 days. The wound closure percent calculated during the course of the experiment at days 1, 7 and 14 was remarkably increased as a result of treatment of non-diabetic and diabetic wounded rats with quercetin and LLLT; the treatment with both was the most potent. The elevated blood glucose and the lowered serum insulin levels were significantly improved in diabetic wounded rats treated with quercetin and LLLT as compared to the diabetic wounded control. The histological findings indicated that the wounded skin showed a marked increase in collagen fibers which become well oriented in sub-epidermal tissue, intact epidermis and presence of hyperplasia covering well-developed granulation tissue in the wounded rats treated with quercetin and LLLT as compared to the corresponding wounded control. The elevated levels of serum pro-inflammatory cytokines, IL-1ß and TNF-α, as well as PGE-2 and LTB-4 were decreased in non-diabetic and diabetic wounded rats with quercetin and LLLT while the lowered level of serum anti-inflammatory cytokine, IL-10, was increased. The augmented oxidative stress represented by increased serum lipid peroxides level was decreased and the serum level of non-enzymatic anti-oxidant glutathione was increased as a result of treatment with quercetin and LLLT. Thus, it can be suggested that the improvements in glycemic state, cytokines involved in inflammation and antioxidant defense system as well as structural reorganization after treatment with quercetin and LLLT may play pivotal roles in promoting the wound healing process. The study also concluded that the treatment with quercetin in association with LLLT was better in improving wound healing in non-diabetic and diabetic rats than the use of either of each.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Mediadores da Inflamação/antagonistas & inibidores , Terapia com Luz de Baixa Intensidade/métodos , Estresse Oxidativo/efeitos dos fármacos , Quercetina/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Terapia Combinada/métodos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Estresse Oxidativo/fisiologia , Quercetina/farmacologia , Ratos , Cicatrização/fisiologia
8.
Chem Biol Interact ; 285: 76-84, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29481770

RESUMO

There are global increased interests to identify novel agents that can possess anti-tumor effects or maximize the anti-tumor effects of low doses for conventional anti-cancer drugs. The aim of this study was to investigate anti-tumor effects and protective role of isolated hesperidin from sweet orange on doxorubicin-induced toxicity in Ehrlich ascites carcinoma (EAC) bearing mice. Tumor cells were injected into Swiss albino mice followed by hesperidin administration either alone or in combination with doxorubicin. Biochemical parameters on serum and hepatic were measured. In addition, the effect of hesperidin on apoptotic genes (Caspase3 and Bax) and anti-apoptotic gene (Bcl2) on tumor cells were evaluated by RT- PCR. The results showed that addition of hesperidin to doxorubicin-induced higher anti-tumor responses than treatment with hesperidin or doxorubicin alone. Hesperidin and doxorubicin in combination prolonged the life span of EAC tumor-bearing mice which was associated with a decrease in the number of viable tumor cells and increases in dead tumor cells number. In addition, co-administration of hesperidin with doxorubicin ameliorated the alteration in serum ALT, AST, ALP, GGT and LDH activities, total protein, albumin, creatinine, urea and total lipids concentrations. Moreover, hesperidin alone and in combination with doxorubicin-treated group decreased hepatic, TBARS level significantly as compared with tumor bearing mice and doxorubicin treated group. In contrast, hesperidin alone and combined with doxorubicin ameliorated total antioxidant capacity, reduced glutathione level, and antioxidant enzymes activities such as GPx and CAT in liver tissues. Moreover, hesperidin induced apoptosis of tumor cells which appeared as DNA fragmentation by down-regulation of Bcl2 as anti-apoptotic gene and stimulation of Caspase3 and Bax genes expression as apoptotic genes. In conclusion, Egyptian citrus peels are a rich source of the antioxidant hesperidin. Moreover, it can ameliorate the cytotoxic effect of doxorubicin while enhancing its anti-tumor effect.


Assuntos
Ascite/tratamento farmacológico , Carcinoma de Ehrlich/tratamento farmacológico , Hesperidina/uso terapêutico , Animais , Peso Corporal/efeitos dos fármacos , Hesperidina/farmacologia , Masculino , Camundongos , Carga Tumoral/efeitos dos fármacos
9.
Anal Chem ; 89(1): 910-915, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-27959505

RESUMO

96-Well plate has been the traditional method used for screening drug compounds libraries for potential bioactivity. Although this method has been proven successful in testing dose-response analysis, the microliter consumption of expensive reagents and hours of reaction and analysis time call for innovative methods for improvements. This work demonstrates a droplet microfluidic platform that has the potential to significantly reduce the reagent consumption and shorten the reaction and analysis time by utilizing nanoliter-sized droplets as a replacement of wells. This platform is evaluated by applying it to screen drug compounds that inhibit the tau-peptide aggregation, a phenomena related to Alzheimer's disease. In this platform, sample reagents are first dispersed into nanolitre-sized droplets by an immiscible carrier oil and then these droplets are trapped on-demand in the downstream of the microfluidic device. The relative decrease in fluorescence through drug inhibition is characterized using an inverted epifluorescence microscope. Finally, the trapped droplets are released on-demand after each test by manipulating the applied pressures to the channel network which allows continuous processing. The testing results agree well with that obtained from 96-well plates with much lower sample consumption (∼200 times lower than 96-well plate) and reduced reaction time due to increased surface volume ratio (2.5 min vs 2 h).


Assuntos
Compostos Azo/análise , Avaliação Pré-Clínica de Medicamentos/métodos , Técnicas Analíticas Microfluídicas , Inibidores de Proteínas Quinases/análise , Compostos Azo/farmacologia , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Técnicas Analíticas Microfluídicas/instrumentação , Tamanho da Partícula , Agregados Proteicos/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia
10.
Mar Pollut Bull ; 111(1-2): 435-442, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26902685

RESUMO

Two microbial isolates from oil polluted Red Sea water in Egypt, designated as RS-Y1 and RS-F3, were found capable of degrading Belayim mix (BX) crude oil. Strains RS-Y1 and RS-F3 were assigned to the genera Lipomyces tetrasporus and Paecilomyces variotii based on their morphological and physiological characteristics. Both isolates were compared for the biodegradation of crude petroleum-oil hydrocarbons in basal salt medium supplemented with 5% (w/v) of BX-crude oil. Gas chromatography profile showed that the biodegradation of total petroleum hydrocarbons (TPHs) inoculated with L. tetrasporus (68.3%) and P. variotii (58.15%) along with their consortium (66%) significantly reduced TPHs levels as compared to the control after 30days. L. tetrasporus (44.5%) was more effective than P. variotii strain (32.89%) in reducing the unresolved complex mixtures (UCM) content from the medium. Both isolates exhibited a strong growth over a wide range of salinity (5-45g/L NaCl).


Assuntos
Lipomyces/metabolismo , Paecilomyces/metabolismo , Poluição por Petróleo , Petróleo/metabolismo , Poluição da Água , Biodegradação Ambiental , Egito , Hidrocarbonetos/metabolismo , Lipomyces/crescimento & desenvolvimento , Lipomyces/isolamento & purificação , Paecilomyces/crescimento & desenvolvimento , Paecilomyces/isolamento & purificação , Água do Mar/microbiologia
11.
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
12.
Biol Trace Elem Res ; 160(3): 392-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25022246

RESUMO

The present study was carried out to investigate the protective effect of Physalis peruviana L. (family Solanaceae) against cadmium-induced neurotoxicity in rats. Adult male Wistar rats were randomly divided into four groups. Group 1 was used as control. Group 2 was intraperitoneally injected with 6.5 mg/kg bwt of cadmium chloride for 5 days. Group 3 was treated with 200 mg/kg bwt of methanolic extract of Physalis (MEPh). Group 4 was pretreated with MEPh 1 h before cadmium for 5 days. Cadmium treatment induced marked disturbances in neurochemical parameters as indicating by significant (p < 0.05) reduction in dopamine (DA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in cerebellum, hippocampus, and cerebral cortex and enhanced significantly (p < 0.05) the levels of lipid peroxidation and nitric oxide in the brain. Cadmium treatment also decreased the amount of nonenzymatic and enzymatic antioxidants significantly (p < 0.05). Pretreatment with MEPh resulted in significant (p < 0.05) decreases in lipid peroxidation and nitric oxide levels and restored the amount of glutathione successfully. Although, preadministration of MEPh also brought the activities of cellular antioxidant enzymes, namely superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase significantly (p < 0.05) to the control levels, as well as the levels of Ca(2+), Cl(-), DA, 5-HT, and serotonin metabolite, 5-HIAA. These data indicated that Physalis has a beneficial effect in ameliorating the cadmium-induced oxidative neurotoxicity in the brain of rats.


Assuntos
Encéfalo , Cloreto de Cádmio/toxicidade , Síndromes Neurotóxicas , Physalis/química , Extratos Vegetais/farmacologia , Animais , Antioxidantes/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Química Encefálica/efeitos dos fármacos , Cádmio/toxicidade , Dopamina/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/prevenção & controle , Oxirredutases/metabolismo , Extratos Vegetais/química , Ratos , Ratos Wistar , Serotonina/metabolismo
13.
Artigo em Chinês | WPRIM | ID: wpr-672709

RESUMO

Objective:To investigate the adverse effect of exposure to acetylsalicylic acid (ASA), diazinon (DIA) and their combination on oxidant/antioxidant status in rat erythrocytes and the ameliorating role of selenium (Se). Methods: Rats were oral administered ASA at the maximum administration dose (1 350 mg/personal/d=2.5 mg/kg body weight/d), DIA at a dose of 20 mg/kg body weight/d and Se at a dose of 200 μg/kg body weight/d and their combinations for 28 consecutive d. Results: Administration of DIA, ASA and ASA+DIA lead to a significant increment (P≤0.05) in lipid peroxidation as evidenced by the increase in erythrocytes MDA levels by 61.8%, 20.79%and 105.62%, respectively. Co-administration of Se to treated rats modulated the augmentation of MDA levels. Administration of DIA, ASA and ASA+DIA lead to significant decreases (P≤0.05) in the activities of catalase, superoxide dismutase and glutathione peroxidase enzymes when compared to the control group. The most influence and decreases in the activities of the aforementioned enzymes were observed in the treatments of ASA+DIA by 30.53%, 43.42%and 48.31%, respectively. However, co-administration of Se mitigated the significant decreases of superoxide dismutase, catalase and glutathione peroxidase activities to by 14.47%, 15, 36%and 12.29%. Conclusions: It can be concluded that DIA and ASA induced oxidative stress and lipid peroxidation in rat erythrocytes. The results reveal the pronounced ameliorating effect of Se in DIA and ASA intoxicated rats. It is supposed that antioxidant supplementation may be beneficial for the people using ASA for longer periods and exposure to pesticides.

14.
Bioorg Med Chem Lett ; 21(19): 5881-7, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21873056

RESUMO

A group of 2-substituted N-(naphth-1-ylmethyl)pyrimidin-4-amines (6a-k) and N-benzhydrylpyrimidin-4-amines (7a-k) in conjunction with varying steric and electronic properties at the C-2 position were designed, synthesized and evaluated as dual cholinesterase and amyloid-ß (Aß)-aggregation inhibitors. The naphth-1-ylmethyl compound 6f (2-(4-cyclohexylpiperazin-1-yl)-N-(naphth-1-ylmethyl)pyrimidin-4-amine) exhibited optimum dual ChE (AChE IC(50)=8.0 µM, BuChE IC(50)=3.9 µM) and hAChE-promoted Aß-aggregation inhibition (30.8% at 100 µM), whereas in the N-benzhydryl series, compound 7f (N-benzhydryl-2-(4-cyclohexylpiperazin-1-yl)pyrimidin-4-amine) exhibited optimum combination of dual ChE (AChE IC(50)=10.0 µM, BuChE IC(50)=7.6µM) and hAChE-promoted Aß-aggregation inhibition (32% at 100 µM). These results demonstrate that a 2,4-disubstituted pyrimidine ring serves as a suitable template to target multiple pathological routes in AD, with a C-2 cyclohexylpiperazine substituent providing dual ChE inhibition and potency whereas a C-4 diphenylmethane substituent provides Aß-aggregation inhibition.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Compostos Benzidrílicos/síntese química , Compostos Benzidrílicos/farmacologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Acetilcolinesterase/metabolismo , Compostos Benzidrílicos/química , Compostos Benzidrílicos/metabolismo , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Relação Dose-Resposta a Droga , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Modelos Moleculares , Estrutura Molecular , Terapia de Alvo Molecular , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/prevenção & controle , Placa Amiloide/tratamento farmacológico , Placa Amiloide/patologia , Placa Amiloide/prevenção & controle , Pirimidinas/química , Pirimidinas/metabolismo , Relação Estrutura-Atividade
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