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1.
PLoS One ; 17(8): e0272776, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35947632

RESUMO

Hepatocellular carcinoma (HCC) is one of the world's most risky diseases due to the lack of clear and cost-effective therapeutic targets. Currently, the toxicity of conventional chemotherapeutic medications and the development of multidrug resistance is driving research into targeted therapies. The nano-biomedical field's potential for developing an effective therapeutic nano-sized drug delivery system is viewed as a significant pharmaceutical trend for the encapsulation and release of numerous anticancer therapies. In this regard, current research is centered on the creation of biodegradable chitosan nanoparticles (CSNPs) for the selective and sustained release of bee venom into liver cancer cells. Furthermore, surface modification with polyethylene glycol (PEG) and GE11 peptide-conjugated bee venom-CSNPs allows for the targeting of EGFR-overexpressed liver cancer cells. A series of in vitro and in vivo cellular analyses were used to investigate the antitumor effects and mechanisms of targeted bee venom-CSNPs. Targeted bee venom-CSNPs, in particular, were found to have higher cytotoxicity against HepG2 cells than SMMC-7721 cells, as well as stronger cellular uptake and a substantial reduction in cell migration, leading to improved cancer suppression. It also promotes cancer cell death in EGFR overexpressed HepG2 cells by boosting reactive oxygen species, activating mitochondria-dependent pathways, inhibiting EGFR-stimulated MEK/ERK pathway, and elevating p38-MAPK in comparison to native bee venom. In hepatocellular carcinoma (HCC)-induced mice, it has anti-cancer properties against tumor tissue. It also improved liver function and architecture without causing any noticeable toxic side effects, as well as inhibiting tumor growth by activating the apoptotic pathway. The design of this cancer-targeted nanoparticle establishes GE11-bee venom-CSNPs as a potential chemotherapeutic treatment for EGFR over-expressed malignancies. Finally, our work elucidates the molecular mechanism underlying the anticancer selectivity of targeted bee venom-CSNPs and outlines therapeutic strategies to target liver cancer.


Assuntos
Venenos de Abelha , Carcinoma Hepatocelular , Quitosana , Neoplasias Hepáticas , Nanopartículas , Animais , Venenos de Abelha/farmacologia , Venenos de Abelha/uso terapêutico , Carcinoma Hepatocelular/patologia , Quitosana/uso terapêutico , Receptores ErbB/metabolismo , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Peptídeos/metabolismo
2.
Molecules ; 26(22)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34833928

RESUMO

The study of diabetes mellitus (DM) patterns illustrates increasingly important facts. Most importantly, they include oxidative stress, inflammation, and cellular death. Up to now, there is a shortage of drug therapies for DM, and the discovery and the development of novel therapeutics for this disease are crucial. Medicinal plants are being used more and more as an alternative and natural cure for the disease. Consequently, the objective of this review was to examine the latest results on the effectiveness and protection of natural plants in the management of DM as adjuvant drugs for diabetes and its complex concomitant diseases.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Animais , Diabetes Mellitus/metabolismo , Humanos , Insulina/metabolismo , Fitoterapia/métodos , Extratos Vegetais/química
3.
Pharmaceutics ; 13(11)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34834352

RESUMO

Numerous epidemiological findings have repeatedly established associations between Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease. Targeting different pathways in the brain with T2DM-therapy offers a novel and appealing strategy to treat diabetes-related neuronal alterations. Therefore, here we investigated the capability of a natural compound, curcumin nanoparticle (CurNP), and a biomedical metal, zinc oxide nanoparticle (ZnONP), to alleviate hippocampal modifications in T2DM-induced rats. The diabetes model was induced in male Wistar rats by feeding a high-fat diet (HFD) for eight weeks followed by intraperitoneal injection of streptozotocin (STZ). Then model groups were treated orally with curcumin, zinc sulfate, two doses of CurNP and ZnONP, as well as metformin, for six weeks. HFD/STZ-induced rats exhibited numerous biochemical and molecular changes besides behavioral impairment. Compared with model rats, CurNP and ZnONP boosted learning and memory function, improved redox and inflammation status, lowered Bax, and upregulated Bcl2 expressions in the hippocampus. In addition, the phosphorylation level of the MAPK/ERK pathway was downregulated significantly. The expression of amyloidogenic-related genes and amyloid-beta accumulation, along with tau hyperphosphorylation, were lessened considerably. In addition, both nanoparticles significantly improved histological lesions in the hippocampus. Based on our findings, CurNP and ZnONP appear to be potential neuroprotective agents to mitigate diabetic complications-associated hippocampal toxicity.

4.
Sci Rep ; 11(1): 20677, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34667196

RESUMO

The present study was carried out to investigate the therapeutic effect of synthesized naturally compounds, curcumin nanoparticles (CurNPs) and metal oxide, zinc oxide nanoparticles (ZnONPs) on a high-fat diet (HFD)/streptozotocin (STZ)-induced hepatic and pancreatic pathophysiology in type 2 diabetes mellitus (T2DM) via measuring AKT pathway and MAPK pathway. T2DM rats were intraperitoneally injected with a low dose of 35 mg/kg STZ after being fed by HFD for 8 weeks. Then the rats have orally received treatments for 6 weeks. HFD/STZ-induced hepatic inflammation, reflected by increased phosphorylation of p38-MAPK pathway's molecules, was significantly decreased after nanoparticle supplementation. In addition, both nanoparticles significantly alleviated the decreased phosphorylation of AKT pathway. Further, administration of ZnONPs, CurNPs, conventional curcumin, and ZnSO4 (zinc sulfate), as well as metformin, effectively counteracted diabetes-induced oxidative stress and inflammation in the internal hepatic and pancreatic tissues. Based on the results of the current study, ZnONPs and CurNPs could be explored as a therapeutic adjuvant against complications associated with T2DM. Both nanoparticles could effectively delay the progression of several complications by activating AKT pathway and down-regulating MAPK pathway. Our findings may provide an experimental basis for the application of nanoparticles in the treatment of T2DM with low toxicity.


Assuntos
Curcumina/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Nanopartículas/administração & dosagem , Obesidade/metabolismo , Óxido de Zinco/farmacologia , Animais , Antioxidantes/metabolismo , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Insulina/metabolismo , Resistência à Insulina/fisiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Metformina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Estreptozocina/farmacologia
5.
PLoS One ; 15(11): e0241509, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33166302

RESUMO

OBJECTIVES: Infertility is a global health problem with about 15 percent of couples involved. About half of the cases of infertility are related to male-related factors. A major cause of infertility in men is oxidative stress, which refers to an imbalance between levels of reactive oxygen species (ROS) and antioxidants. Erectile dysfunction drugs (EDD), known as phosphodiesterase inhibitors (PDEIs), have been used for the treatment of ED. It has been shown that oxidative stress plays an important role in the progression of erectile dysfunction. Oxidative stress can be alleviated or decreased by non-antioxidants and antioxidant enzymes. The present study was undertaken to determine if these compounds could have a role in the incidence of infertility, especially after long-term use. Therefore, the present study aims to investigate the effect of EDD on the activities of antioxidant enzymes, free radical levels as well as the protein expression of different cytochrome P450 isozymes involved in the steroidogenesis of different hormones. In addition, the activity of both 17ß-hydroxysteroid dehydrogenase and 17-ketosteroid reductase were assayed. The architectures of both livers and testes cells were investigated under the influence of EDD. METHODS: A daily dose of Sildenafil (1.48 mg/kg), Tadalafil (0.285 mg/kg) and Vardenafil (0.285 mg/kg) were administered orally to male rabbits for 12 week. Western immunoblotting, ELISA, spectrophotometric and histopathological techniques were used in this study. RESULTS: The present study showed that Sildenafil, Vardenafil, and Tadalafil treatments significantly decreased the levels of glutathione and free radicals in both livers and testes of rabbits. Also, Vardenafil and Sildenafil induced the activity of superoxide dismutase and catalase whereas, glutathione S-transferase, glutathione reductase, and glutathione peroxidase activities inhibited in livers of rabbits. The protein expression of cytochrome P450 isozymes (CYP 11A1, 21A2, and 19C) which are involved in the steroidogenesis was markedly changed in both livers and testes of rabbits after their treatments for 12 weeks. After the treatment of rabbits with these medication, the protein expression of CYP11A1 was slightly down-regulated in both livers and testes except Sildenafil up-regulated such protein expression. In addition, the protein expressions of CYP11A1 and CYP 19C in both livers and testes were down-regulated after treatment of rabbits with Sildenafil, Vardenafil, and Tadalafil for 12 weeks. Also, these drugs inhibited the activity of both 17ß-hydroxysteroid dehydrogenase and 17-ketosteroid reductase in testes of rabbits. Moreover, Sildenafil, Vardenafil, and Tadalafil-treated rabbits showed a decrease in spermatocytes and the number of sperms in the testes. CONCLUSIONS: It is concluded that ED drugs induced the activities of both SOD and catalase which consequently decreased MDA level. Decrement in MDA levels and oxidative stress could therefore sustain the erection for a long period of time. On the other hand, it is not advised to use these drugs for a long-term since the protein expressions of CYP isozymes involved in steroidogenesis as well as the numbers of spermatocytes in testes were decreased.


Assuntos
Antioxidantes/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Disfunção Erétil/tratamento farmacológico , Estresse Oxidativo , Esteroides/biossíntese , Animais , Glutationa/metabolismo , Isoenzimas/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Coelhos , Citrato de Sildenafila/farmacologia , Citrato de Sildenafila/uso terapêutico , Tadalafila/farmacologia , Tadalafila/uso terapêutico , Testículo/efeitos dos fármacos , Testículo/patologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Dicloridrato de Vardenafila/farmacologia , Dicloridrato de Vardenafila/uso terapêutico
6.
PLoS One ; 14(8): e0220779, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31442295

RESUMO

BACKGROUND AND OBJECTIVES: In the present article, we explore a novel strategy of selenium nanoparticles (Se-NPs) for the treatment of type 2 diabetes mellitus (T2DM) by investigating the effect of Se-NPs alone and in combination with standard anti-diabetic drug metformin (MET) in high-fat diet/streptozotocin (HFD/STZ)-induced T2DM. METHODS: HFD was supplemented daily to experimental rats for 8 weeks, followed by a single low dose injection of 35 mg/kg of STZ to induce T2DM. The synergistic effect of the different therapeutic strategies on diabetic complications was evaluated after the Se-NPs and MET administration for 8 weeks. Molecular and biochemical analyses were conducted to figure out the effectiveness of our treatment on insulin sensitivity, oxidative mediators and inflammatory markers. RESULTS: Our observations demonstrated that HFD/STZ-induced rats have a toxic effect on serum and hepatic tissues resulted in inducing remarkable oxidative damage and hyper-inflammation with a significant disturbance in the insulin signaling pathway. Experimental animals either treated with mono-therapeutic-two doses Se-NPs (0.1 and 0.4 mg/kg) and/or MET (100 mg/kg) alone as well as the combined therapy resulted in a remarkable protective anti-diabetic effect illustrated by significant decreases in fasting blood glucose and insulin levels after 8 weeks treatment. At the same time, the levels of active insulin signaling proteins pIRS1/pAKT/pGSK-3ß/pAMPK were significantly improved. Moreover, Se-NPs exhibited an anti-inflammatory effect by the mitigation of cytokine expression and a balance between oxidative stress and antioxidant status was restored. Furthermore, the anti-diabetic drug MET administration also exhibited a significant improvement in diabetic complications after the treatment period. CONCLUSION: This study provides mightily the mechanism of action of combined Se-NPs and MET as a promising therapeutic alternative that synergistically alleviates most of diabetic complications and insulin resistance.


Assuntos
Antioxidantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Selênio/uso terapêutico , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Sinergismo Farmacológico , Resistência à Insulina , Masculino , Nanopartículas/uso terapêutico , Ratos , Ratos Sprague-Dawley
7.
PLoS One ; 12(5): e0172429, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28505155

RESUMO

BACKGROUND AND OBJECTIVES: Insulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer's progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated. METHODS: T2DM-induced rats were orally and daily administrated 2.0 ml NSO, 100 mg metformin (MT), 0.8 mg glimepiride (GI) and different combinations (100 mg MT & 2.0 ml NSO, 0.8 mg GI & 2.0 ml NSO and 2.0 ml NSO & intraperitoneal injection of 1/100 LD50 of IOMe-AG538) per kg body weight for 21 days. RESULTS: A significant increase in the brain lipid peroxidation and decrease in the antioxidant status with peripheral and central production of pro-inflammatory mediators were observed in diabetes-induced rats. The brain AChE was activated and associated with diminished brain glucose level and cholinergic function. In addition, the brain insulin resistance and the attenuated insulin signaling pathway (p-IRS/ p-AKT/p-GSK-3ß) were accompanied by an augmentation in GSK-3ß level, which in turn may contribute in the extensive alterations of Tau phosphorylation along with changes in PP2A level. Furthermore, neuronal loss and elevation in Aß-42 plaque formation were observed due to a low IDE formation and an increased expression of p53, BACE1 and APP with diminished ADAM10, SIRT1 and BDNF levels. The expression profile of AD-related miRNAs in sera and brain tissues displayed its neuro-protection role. The treatment of diabetes-induced rats with NSO and the anti-diabetic drugs alone and/or in combination have the potential to suppress the oxidative stress, the pro-inflammatory mediators and amyloidogenic pathway. Moreover, it lowers the insulin receptor inhibitory effect of IOMe-AG538 and modifies the insulin-signaling pathway. Therefore, it prevents the neurotoxicity, amyloid plaque formation and Tau hyper-phosphorylation and restores AD-related miRNA normal levels. CONCLUSION: These data suggest that NSO or its combined treatments with anti-diabetic drugs have a possible benefit as disease modifying agents for the insulin resistance in the brain through enhancing brain insulin signaling pathway.


Assuntos
Encéfalo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Insulina/metabolismo , Estresse Oxidativo , Transdução de Sinais , Animais , Antioxidantes/metabolismo , Biomarcadores , Encéfalo/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Expressão Gênica , Perfilação da Expressão Gênica , Hipoglicemiantes/farmacologia , Mediadores da Inflamação/metabolismo , Resistência à Insulina/genética , Masculino , MicroRNAs/genética , Oxidantes/metabolismo , Estresse Oxidativo/genética , Óleos de Plantas/farmacologia , Ratos , Transdução de Sinais/efeitos dos fármacos
8.
Artigo em Inglês | MEDLINE | ID: mdl-28293546

RESUMO

In rats with induced diabetes, Zinc and curcumin treatment showed a significant increase of catalase and a significant decrease of glucose, lipid profile components and arylsulphatases activity compared to the untreated rats. We suggest that dietary zinc and curcumin are promising protective agents for reducing the metabolic defect of diabetes.

9.
Saudi J Kidney Dis Transpl ; 28(2): 325-329, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28352015

RESUMO

Diabetic nephropathy (DN) is one of the leading causes of end-stage renal disease (ESRD). The development and progression of nephropathy is strongly determined by genetic factors, and few genes have been shown to contribute to DN. An insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE) was reported as a candidate gene predisposing to DN and ESRD. Accordingly, we investigated the frequency of ACE I/D polymorphism in 50 patients with DN, of whom 33 had ESRD and compared them with 64 patients with type 2 diabetes mellitus (T2DM) but with normal renal function. Polymerase chain reaction amplification, using specific primers, was performed to genotype ACE I/D. Chi-square test was used to assess the differences between the groups. The frequencies of the ACE genotypes were as follows: 48% D/D, 40% I/D, and 12% I/I in patients with DN in contrast to 32.8% D/D, 45.3% I/D, and 21.9% I/I in T2DM. The distribution of the D/D, D/I, and I/I genotypes did not significantly differ between T2DM and DN. However, having the D allele carried a risk for the development of DN [odds ratio (OD), 1.71, P = 0.054]. On the other hand, the distribution of the D/D, D/I, and I/I genotypes was significantly different between T2DM and ESRD patients, χ2 = 7.23, P = 0.027. This was reflected by the D allele which carried a risk for the development of ESRD (OR, 2.51, P = 0.0057). These findings suggest that the D allele may be considered as a risk factor for both the development of DN and the progression of DN to ESRD in Lebanese population with T2DM.


Assuntos
Nefropatias Diabéticas/genética , Mutação INDEL , Falência Renal Crônica/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/enzimologia , Nefropatias Diabéticas/epidemiologia , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/enzimologia , Falência Renal Crônica/epidemiologia , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de Risco
11.
Oxid Med Cell Longev ; 2016: 2492107, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27579151

RESUMO

The black cumin (Nigella sativa) "NS" or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling.


Assuntos
Antígenos CD/química , Nigella sativa/química , Receptor de Insulina/química , Animais , Diabetes Mellitus Experimental , Dieta Hiperlipídica , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
12.
J Diabetes Metab Disord ; 13(1): 116, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25516848

RESUMO

BACKGROUND: Diabetes mellitus (DM) is characterized by the overproduction of the reactive oxygen species which affects the integrity of the lysosomal membrane affecting lysosomal enzymes. The effect of these species is blocked by some natural products as antioxidants. In the current study, groups of normal and streptozotocin (STZ)-induced diabetic rats were treated by Nigella sativa (NS), olive and canola oils and subjected to the study of arylsulfatases as a model of lysosomal enzymes. The aim of the present study is to investigate the effect of STZ-induced diabetes on arylsulfatases in presence and absence of NS, olive and canola oils. METHODS: Different groups of rats were induced by STZ, treated with different oils and compared to their corresponding control group. All groups were subjected for the assays of blood glucose, insulin, catalase and arylsulfatases. A comparative kinetic study of arylsulfatses was performed to detect the alteration of catalytic characterization. RESULTS: The results demonstrated that diabetes causes a significant elevation in the level of hepatic arylsulfatase B and a significant reduction of hepatic catalase as an antioxidant enzyme. NS and olive oils returned catalase and arylsulfatase B activities back near to normal by fixing their catalytic properties. Furthermore, the maximum velocity of arylsulfatases A and B was significantly elevated in the induced diabetes, whereas their Km values were significantly changed. The treatment of diabetic rats by NS and olive oils reduced the degree of significance. CONCLUSION: Diabetes induces significant alterations of the catalytic characters of arylsulfatases and some oils decrease this alteration through an antioxidant-mediated effect.

13.
Biochem Genet ; 52(1-2): 15-28, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23877192

RESUMO

This study included 20 selected female patients with breast cancer, 30 of their female relatives (sisters and daughters), and 10 healthy females as a control group. Genomic DNA was extracted from peripheral blood lymphocytes of all the subjects, and the polymerase chain reaction was carried out using specific primers for BRCA1 (exons 2 and 8) and BRCA2 (exons 9, 11, and 21). The mutations were detected using a single-strand conformation polymorphism assay and heteroduplex analysis. Finally, the sample variants and their controls were sequenced. Mutations were detected in 44% of the study population, with 18% found in the BRCA1 gene and 26% attributed to BRCA2. Five sequence variants were identified, including two frameshift mutations, one nonsense mutation, and two missense mutations. Therefore, we conclude that germline mutations in two major genes, BRCA1 and BRCA2, may have an important influence on the predisposition and development of familial breast cancer.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Mutação Puntual , Adulto , Idoso , Sequência de Aminoácidos , Estudos de Casos e Controles , Egito , Éxons , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Análise de Sequência , Adulto Jovem
14.
Med Oncol ; 30(3): 673, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23912699

RESUMO

In this article, we present a study on the levels of epidermal growth factor (EGF), its phosphorylated receptor (p-EGFR) and transforming growth factor-ß1 (TGF-ß1) in the sera of patients with hepatocellular carcinoma (HCC) and chronic hepatitis C (CHC) infection. The results reveal significant higher serum levels of EGF and TGF-ß1 in patients with HCC compared to their level in patients with CHC infection and control subjects. The levels of p-EGFR in HCC and CHC patients show a highly significant difference between patients. Based on the best cutoff value of 914 pg/ml, EGF shows 63.3 % sensitivity and 87.5 % specificity for HCC patients where the area under the curve is 0.81. The p-EGFR shows sensitivity of 63.3 % and specificity of 100 % where the area under the curve is 0.87 for HCC patients based on the best cutoff value of 39 U/mg protein. The best cutoff value (370 pg/ml) for serum TGF-ß1 displays sensitivity of 86.7 % and specificity of 100 %, where the area under the curve is 0.97 for HCC patients.


Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Fator de Crescimento Epidérmico/sangue , Receptores ErbB/sangue , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Fator de Crescimento Transformador beta1/sangue , Adulto , Idoso , Carcinoma Hepatocelular/virologia , Hepacivirus , Humanos , Neoplasias Hepáticas/virologia , Pessoa de Meia-Idade , Adulto Jovem
15.
Acta Biochim Pol ; 59(4): 575-80, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23074703

RESUMO

Coccidiosis is one of the most common parasitic diseases affecting many species of domestic animals. This disease has a major economic significance and the search for new compounds having anticoccidial activity is of great importance. In this article, different levels of protection from coccidian infection by Eimeria stiedae were developed in rabbits by treatment with compounds incorporating the skeleton of thiourea. These compounds include 4,5-diphenylimidazole-2-thione (1), 4,5-Diphenyl-1,2,4-triazole-3-thiol (2) and 5-(2-Hydroxyphenyl)-4-phenyl-1,2,4-triazole-3-thiol (3) compared to the anticoccidial drug toltrazuril as a reference compound. Compounds 1-3 inhibit coccidiosis-induced activity of α-glucosidase. The protection from coccidial infection by compound 1 was higher than that shown for compounds 2 and 3. These data suggest that diazole and triazole thione derivatives have a mimetic effect for anticoccidial drugs through their inhibition of glycosidases.


Assuntos
Coccidiose , Eimeria , Glicosídeo Hidrolases/sangue , Tionas/farmacologia , Animais , Coccidiose/tratamento farmacológico , Coccidiose/microbiologia , Coccidiose/parasitologia , Coccidiose/veterinária , Coccidiostáticos/farmacologia , Eimeria/efeitos dos fármacos , Eimeria/enzimologia , Eimeria/patogenicidade , Inibidores Enzimáticos/farmacologia , Glicosídeo Hidrolases/antagonistas & inibidores , Coelhos , Tionas/síntese química
16.
J. physiol. biochem ; 68(2): 219-227, jun. 2012.
Artigo em Inglês | IBECS | ID: ibc-122341

RESUMO

Calcium is an essential nutrient required for critical biological functions. Calcium supplementation is to be evaluated using immature female rats. The present study focused on some blood parameters, gonadal development and bone structure. Forty immature female Sprague-Dawley rats were randomly divided into four equal-sized groups (80 g average body weight) to receive calcium chloride dihydrate (group I: control; groups II, III and IV: received 20 mg, 40 mg and 60 mg per kg body weight, respectively) for 5 weeks. Rats were decapitated, and their trunk blood was sampled for biochemical assays. Cholesterol, triglycerides, glucose and calcium were measured. Gonadal and bone structure were histologically evaluated. Results revealed that treatment of developing female rats with three calcium doses used have no marked effect on the serum calcium and cholesterol levels. However, serum triglyceride level and body weight gain are significantly decreased in rats treated with all of the three calcium doses. Serum glucose level showed a marked increase in animals treated with the higher calcium doses. Moreover, observable histological alterations are recognized in the ovaries. Bones of the experimental animals also showed morphological alterations. These results suggest that increasing calcium supplementation decreases triglycerides and percentage body weight gain and positively affects the bone and gonadal development (AU)


Assuntos
Animais , Ratos , Cloreto de Cálcio/farmacocinética , Desenvolvimento Sexual , Desenvolvimento Ósseo , Estudos de Casos e Controles , Colesterol/sangue , Triglicerídeos/sangue , Cálcio/sangue
17.
J Physiol Biochem ; 68(2): 219-27, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22139999

RESUMO

Calcium is an essential nutrient required for critical biological functions. Calcium supplementation is to be evaluated using immature female rats. The present study focused on some blood parameters, gonadal development and bone structure. Forty immature female Sprague-Dawley rats were randomly divided into four equal-sized groups (80 g average body weight) to receive calcium chloride dihydrate (group I: control; groups II, III and IV: received 20 mg, 40 mg and 60 mg per kg body weight, respectively) for 5 weeks. Rats were decapitated, and their trunk blood was sampled for biochemical assays. Cholesterol, triglycerides, glucose and calcium were measured. Gonadal and bone structure were histologically evaluated. Results revealed that treatment of developing female rats with three calcium doses used have no marked effect on the serum calcium and cholesterol levels. However, serum triglyceride level and body weight gain are significantly decreased in rats treated with all of the three calcium doses. Serum glucose level showed a marked increase in animals treated with the higher calcium doses. Moreover, observable histological alterations are recognized in the ovaries. Bones of the experimental animals also showed morphological alterations. These results suggest that increasing calcium supplementation decreases triglycerides and percentage body weight gain and positively affects the bone and gonadal development.


Assuntos
Osso e Ossos/citologia , Cloreto de Cálcio/administração & dosagem , Osteogênese/efeitos dos fármacos , Ovário/efeitos dos fármacos , Animais , Glicemia , Osso e Ossos/anatomia & histologia , Osso e Ossos/efeitos dos fármacos , Cálcio/sangue , Contagem de Células , Tamanho Celular/efeitos dos fármacos , Colesterol/sangue , Suplementos Nutricionais , Feminino , Osteócitos/citologia , Osteócitos/efeitos dos fármacos , Ovário/citologia , Ovário/crescimento & desenvolvimento , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue , Aumento de Peso/efeitos dos fármacos
18.
Genet Test Mol Biomarkers ; 15(6): 423-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21385088

RESUMO

Mutations in the genes encoding enzymes involved in the metabolism of chemical carcinogens can significantly affect the risk of cell transformation and cancer development. The resident Lebanese population has experienced a sharp increase in cancer incidence within the last few years. The relationship between gene polymorphisms of metabolic enzymes and gastrointestinal (GI) cancer incidence was not previously investigated. The aim of this study was to investigate the relationship between CYP1A1, CYP2E1, and GSTM1 gene polymorphisms and GI cancer incidence among Lebanese. Blood and/or paraffin-embedded biopsy samples were collected from patients and healthy controls. The genotypes were determined by polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. The results of the present case-control study show that the studied Lebanese population generally resembles Caucasian populations with respect to the considered polymorphisms. Further, the GSTM1*0/*0 genotype is a significant risk factor for gastric (odds ratio = 4.1; 95% confidence interval: 1.2-14.5) and colorectal cancers (odds ratio = 3.8; 95% confidence interval: 1.7-8.5); on the other hand, CYP1A1*2A and CYP2E1*6 alone are not significantly associated with GI cancer development, although CYP1A1*2A was more frequent among patients. A remarkable and statistically significant 36.5-fold increase in the risk of gastric cancer was observed among patients with CYP1A1*2A/*2A combined with GSTM1*0/*0. The investigation of genetic risk factors and susceptibility gene polymorphisms in Lebanese is helpful for better understanding of GI cancer etiology.


Assuntos
Neoplasias Colorretais/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2E1/genética , Predisposição Genética para Doença , Glutationa Transferase/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/etiologia , Feminino , Genótipo , Humanos , Líbano , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/etiologia
19.
J. physiol. biochem ; 66(4): 291-299, dic. 2010.
Artigo em Inglês | IBECS | ID: ibc-122816

RESUMO

No disponible


Enzymes in mitochondria play an important role in biological oxidation and energy production. To understand the effect of schistosomiasis on these important processes, succinate cytochrome creductase (SCR) from control and Schistosoma-infected mice was subjected for investigation. In this article, we report that SCR from Schistosoma-infected mouse showed a significant decrease in its Vmax and K m compared to control using both cytochrome c and 2,6-dichlorophenolindophenol as substrates. Furthermore, the kinetic studies of the purified SCR in the absence and presence of the schistosomicidal drugs praziquantel and Commiphora extract reveal that both drugs have an inhibitory action on the enzyme from the control and Schistosoma-infected mice and praziquantel changes the type of inhibition of SCR towards cytochrome c from mixed type in control to a competitive one in the case of the infection (AU)


Assuntos
Animais , Camundongos , Succinato Citocromo c Oxirredutase/farmacocinética , Esquistossomose/tratamento farmacológico , Schistosoma , Esquistossomicidas/farmacocinética , Modelos Animais de Doenças
20.
J Physiol Biochem ; 66(4): 291-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20680542

RESUMO

Enzymes in mitochondria play an important role in biological oxidation and energy production. To understand the effect of schistosomiasis on these important processes, succinate cytochrome c reductase (SCR) from control and Schistosoma-infected mice was subjected for investigation. In this article, we report that SCR from Schistosoma-infected mouse showed a significant decrease in its Vmax and Km compared to control using both cytochrome c and 2,6-dichlorophenolindophenol as substrates. Furthermore, the kinetic studies of the purified SCR in the absence and presence of the schistosomicidal drugs praziquantel and Commiphora extract reveal that both drugs have an inhibitory action on the enzyme from the control and Schistosoma-infected mice and praziquantel changes the type of inhibition of SCR towards cytochrome c from mixed type in control to a competitive one in the case of the infection.


Assuntos
Esquistossomose/enzimologia , Esquistossomicidas/uso terapêutico , Succinato Citocromo c Oxirredutase/antagonistas & inibidores , Succinato Citocromo c Oxirredutase/química , 2,6-Dicloroindofenol/química , Animais , Temperatura Alta , Técnicas In Vitro , Cinética , Masculino , Camundongos , Mitocôndrias/enzimologia , Praziquantel/farmacologia , Reprodutibilidade dos Testes , Temperatura
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