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1.
Andrologia ; 54(8): e14456, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35560246

RESUMO

Varieties of studies have been used to investigate the health benefits of Spirulina (Arthrospira platensis); however, more research is needed to examine if its nano form may be utilized to treat or prevent several chronic diseases. So, we designed this study to explore the effect and the cellular intracellular mechanisms by which Arthrospira platensis Nanoparticles (NSP) alleviates the testicular injury induced by diabetes in male Wistar rats. Eighty Wistar male rats (n = 80) were randomly allocated into eight groups. Group 1 is untreated rats (control), Group 2 including STZ-induced diabetic rats with 65 mg/kg body weight STZ (STZ-diabetic), Group 3-5: including diabetic rats treated with NSP1, NSP2, and NSP3 at 0.25, 0.5, and 1 mg/kg body weight, respectively, once daily orally by the aid of gastric gavage for 12 consecutive weeks and groups 6-8 include normal rats received NSP (0.25, 0.5, and 1 mg/kg body weight once daily orally. The identical volume of normal saline was injected into both control and diabetic rats. After 12 weeks of diabetes induction, the rats were killed. According to our findings, NSP administration to diabetic rats enhances the total body weight and the weight of testes and accessory glands; in addition, NSP significantly reduced nitric oxide and malondialdehyde in testicular tissue improved sperm parameters. Intriguingly, it raises testicular GSH and SOD activity by a significant amount (p < 0.05). As well, Oral administration of NSP to diabetic rats resulted in a decrease in the blood glucose levels, HA1C, induced in the diabetic group, which overcame the diabetic complications NSP caused down-regulation of apoptotic genes with upregulation of BCL-2 mRNA expression (p < 0.05) and prominent up-regulation of steroidogenesis genes expression level in testes in comparison to the diabetic rats which resulted in improving the decreased levels of testosterone hormone, FSH, and LH induced by diabetes. In the same way, our histopathological findings support our biochemical and molecular findings; in conclusion, NSP exerted a protective effect against reproductive dysfunction induced by diabetes not only through its high antioxidant and hypoglycemic action but also through its down-regulation of Apoptotic genes and up-regulation of steroidogenesis regulatory genes expression level in diabetic testes.


Assuntos
Diabetes Mellitus Experimental , Nanopartículas , Spirulina , Doenças Testiculares , Animais , Antioxidantes/farmacologia , Peso Corporal , Diabetes Mellitus Experimental/metabolismo , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Sêmen/metabolismo , Spirulina/química , Spirulina/metabolismo , Doenças Testiculares/etiologia , Doenças Testiculares/prevenção & controle , Testículo
2.
Molecules ; 27(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36431959

RESUMO

Previous studies reported disrupted hepatic function and structure following the administration of cyclosporine A (CsA) in humans and animals. Recently, we found that avocado seeds (AvS) ameliorated CsA-induced nephrotoxicity in rats. As a continuation, herein we checked whether AvS could also attenuate CsA-induced hepatotoxicity in rats. Subcutaneous injection of CsA (5 mg/kg) for 7 days triggered hepatotoxicity in rats, as indicated by liver dysfunction, redox imbalance, and histopathological changes. Oral administration of 5% AvS powder for 4 weeks ameliorated CsA-induced hepatotoxicity, as evidenced by (1) decreased levels of liver damage parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin), (2) resumed redox balance in the liver (reduced malondialdehyde (MDA) and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), (3) downregulated hepatic expression of endoplasmic reticulum (ER) stress-related genes (X-box binding protein 1 (XBP1), binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP)), and apoptosis-related genes (Bax and Casp3), (4) upregulated expression of the anti-apoptotic gene Bcl2, (5) reduced DNA damage, and (6) improved liver histology. These results highlight the ability of AvS to ameliorate CsA-induced hepatotoxicity via the inhibition of oxidative stress and proapoptotic ER stress.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Doenças do Sistema Digestório , Hepatopatias , Persea , Humanos , Ratos , Animais , Ciclosporina/efeitos adversos , Persea/metabolismo , Estresse do Retículo Endoplasmático , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Antioxidantes/farmacologia , Estresse Oxidativo , Sementes/metabolismo
3.
Molecules ; 28(1)2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36615218

RESUMO

Triazole-based thiosemicarbazone derivatives (6a-u) were synthesized then characterized by spectroscopic techniques, such as 1HNMR and 13CNMR and HRMS (ESI). Newly synthesized derivatives were screened in vitro for inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives (except 6c and 6d, which were found to be completely inactive) demonstrated moderate to good inhibitory effects ranging from 0.10 ± 0.050 to 12.20 ± 0.30 µM (for AChE) and 0.20 ± 0.10 to 14.10 ± 0.40 µM (for BuChE). The analogue 6i (IC50 = 0.10 ± 0.050 for AChE and IC50 = 0.20 ± 0.050 µM for BuChE), which had di-substitutions (2-nitro, 3-hydroxy groups) at ring B and tri-substitutions (2-nitro, 4,5-dichloro groups) at ring C, and analogue 6b (IC50 = 0.20 ± 0.10 µM for AChE and IC50 = 0.30 ± 0.10 µM for BuChE), which had di-Cl at 4,5, -NO2 groups at 2-position of phenyl ring B and hydroxy group at ortho-position of phenyl ring C, emerged as the most potent inhibitors of both targeted enzymes (AChE and BuChE) among the current series. A structure-activity relationship (SAR) was developed based on nature, position, number, electron donating/withdrawing effects of substitution/s on phenyl rings. Molecular docking studies were used to describe binding interactions of the most active inhibitors with active sites of AChE and BuChE.


Assuntos
Doença de Alzheimer , Inibidores da Colinesterase , Tiossemicarbazonas , Humanos , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/farmacologia , Tiossemicarbazonas/uso terapêutico
4.
Platelets ; 32(5): 642-650, 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32659145

RESUMO

Inherited thrombocytopenias are a heterogeneous group of diseases characterized by a reduced number of platelets and a bleeding tendency that ranges from very mild to life threatening especially in surgery. Mutations in the 5' untranslated region (UTR) of Ankirin repeat domain 26 (ANKRD26) are responsible for autosomal-dominant form of thrombocytopenia, that is known as ANKRD26-related thrombocytopenia (ANKRD26 RT), characterized by a moderate thrombocytopenia with mild propensity to bleeding and predisposition to hematological malignancies including AML and MDS. We included 90 unrelated patients with inherited thrombocytopenia. In addition, we investigated 45 patients with ITP. Peripheral blood and bone marrow samples were collected and examined and molecular detection of mutations in the 5︡ UTR of ANKRD26 gene was performed for all the patients. Also, screening of the mutation and development of myeloid malignancies in the extended series of the affected subjects was done. ANKRD26 mutations were identified in 10% of the patients with inherited thrombocytopenia. The most common types were c.128 G > A and c.127A>T, while no mutations were found in the ITP group. In those affected, the median number of platelets was 69 x109/L (43-106) with normal MPV in most of the patients (9.4-11.6). There was a statistically significant increase in the unexpected high frequency of myeloid malignancies in the extended series of the mutated subjects compared with the ITP group-extended series (P < .001). So, we can conclude that ANKRD26 RT is associated with increased risk for developing myeloid malignancies and ANKRD26 mutations can represent a valuable tool for making therapeutic decisions.


Assuntos
Regiões 5' não Traduzidas/genética , Neoplasias Hematológicas/etiologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Trombocitopenia/complicações , Adolescente , Adulto , Idoso , Criança , Egito , Feminino , Predisposição Genética para Doença , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Adulto Jovem
5.
J Sci Food Agric ; 99(9): 4338-4343, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30828809

RESUMO

BACKGROUND: Contamination of date fruit with mycotoxigenic fungi is a hazardous threat. The present study investigated the effectiveness of natural derivatives for controlling this. Chitosan (Cts) was produced from Aspergillus niger mycelia and characterized and then nanochitosan (NCt) particles were synthesized from fungal Cts. Edible-coating films were formulated based on Cts, NCt, pomegranate peel extract (PPE) and their composites and these were evaluated as antifungal materials against mycotoxigenic fungi, Aspergillus flavus, Aspergillus ochraceus and Fusarium moniliforme. RESULTS: The Cts produced had 88.7% deacetylation, a molecular weight of 24.5 kDa and 98% solubility in diluted acetic acid, whereas the particle diameters of synthesized NCts ranged from 35 to 65 nm. The inhibition zone assay emphasized the antifungal effectiveness of the entire coating films. The most effective agent for preparing edible film was the blend of NCt + PPE followed by Cts + PPE based films. The practical application of antifungal films for date decontamination with respect to mycotoxigenic fungi demonstrates that the films were very effective for controlling the entire fungal strain and preventing growth on the fruits. CONCLUSION: The NCt + PPE and Cts + PPE based films were found to be the most effective because they could completely eliminate the growth of any fungal spore on date fruit after 48 h from the coating experiment. © 2019 Society of Chemical Industry.


Assuntos
Biopolímeros/química , Embalagem de Alimentos/instrumentação , Frutas/microbiologia , Phoeniceae/microbiologia , Extratos Vegetais/química , Aspergillus flavus/efeitos dos fármacos , Aspergillus flavus/crescimento & desenvolvimento , Aspergillus niger/química , Aspergillus niger/metabolismo , Aspergillus ochraceus/efeitos dos fármacos , Aspergillus ochraceus/crescimento & desenvolvimento , Biopolímeros/metabolismo , Biopolímeros/farmacologia , Quitosana/química , Quitosana/metabolismo , Quitosana/farmacologia , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Frutas/química , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Phoeniceae/química , Extratos Vegetais/farmacologia
6.
Toxicol Ind Health ; 33(6): 495-502, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28071525

RESUMO

Exposure to natural and man-made environmental toxins concurrently can pose a greater threat to multiple organs. In the present work, we investigated interactions between deltamethrin (DM) and cadmium (Cd), whose mechanisms of action in humans are poorly understood. Albino mice were randomly divided into four groups, each containing six mice: saline as control, DM-treated, cadmium chloride (CdCl2)-treated, and CdCl2 plus DM treated. After 2 weeks of treatment biochemical and hematological effects, total leukocyte count (TLC), differential leukocyte count, humoral-mediated immune responses, and histopathological studies were conducted. Mice exposed to DM and Cd showed a significant increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Also, DM and Cd administration resulted in suppression of humoral immunity, erythrocyte count, hemoglobin, hematocrit, and TLC. Histopathological evidence revealed hepatic damage, supporting the AST and ALT findings. Cd and DM exhibited an additive type of toxicity. It could be concluded that these toxins either target different cellular pathways, or the individual amounts used in this study were not enough to saturate the toxicological target, thus producing additive effects.


Assuntos
Cloreto de Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Fígado/efeitos dos fármacos , Nitrilas/toxicidade , Piretrinas/toxicidade , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Contagem de Eritrócitos , Fígado/patologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , gama-Glutamiltransferase/metabolismo
7.
Molecules ; 19(10): 15440-51, 2014 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-25264831

RESUMO

A new isoflavonoid, 5,6-dimethoxy-2',3'-methylenedioxy-7-C-ß-d-gluco-pyranosyl isoflavone was isolated from the seeds of Lepidium sativum L. along with two known isoflavonoids, 7-hydroxy-4',5,6-trimethoxyisoflavone and 7-hydroxy-5,6-dimethoxy-2',3'-methylenedioxyisoflavone. The structures of all compounds were elucidated with NMR spectrometry. Compounds 1, 2 and the new isoflavonoid 3 were evaluated for their ability to reduce the hepatotoxicity induced by paracetamol in male rats by reducing the damage and toxicity effects on liver cells with a significant improvement of total antioxidant capacity, normalizing the levels of liver enzymes GSH, SOD, GPX, CAT and GST compared to control group.


Assuntos
Isoflavonas/química , Isoflavonas/farmacologia , Lepidium sativum/química , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Sementes/química , Acetaminofen/efeitos adversos , Animais , Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática , Masculino , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos
8.
Antioxidants (Basel) ; 13(3)2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38539888

RESUMO

Liver fibrosis is a condition characterized by the excessive buildup of scar tissue in the liver. This scarring occurs as a result of chronic liver damage, often caused by conditions such as hepatitis, alcohol abuse, certain metabolic disorders, genetic abnormalities, autoimmunity, and noninfectious diseases such as fatty liver which leads to liver fibrosis. Nanoparticles have gained attention in recent years as potential therapeutic agents for liver fibrosis. They offer unique advantages due to their small size, large surface area, and ability to carry drugs or target specific cells or tissues. Studies have suggested that nanoemulsions may enhance drug delivery systems, enabling targeted drug delivery to specific sites in the liver and improving therapeutic outcomes. In this study, we explore the protective and therapeutic values with phytochemical profiling of the used agro-wastes decaffeinated palm date seeds (Phoenix dactylifera L., PSC) coffee and caffeinated Arabic coffee seeds (Coffea arabica L.; ACS). Both ACS and PSC extracts were converted into nanoemulsion (NE) forms using the oleic acid/Tween 80 system, which was recruited for the purpose of treating a rat model with liver fibrosis. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to record the sizes, morphologies, hydrodynamic diameters, and ζ-potentials of the prepared NE-ACSE and NE-PSCE. Accordingly, the NE-ACSE and NE-PSCE imaged via TEM and their ζ-potentials were recorded at 20.7, 23.3 nm and -41.4, -28.0 mV, respectively. The antioxidant properties were determined with a DPPH scavenging assay. The synthesized NE-PSCE and NE-ACSE were employed to treat a rat model with CCl4-induced liver fibrosis, to estimate the role of each emulsion-based extract in the treatment of liver fibrosis through recording inflammatory parameters, liver functions, antioxidant enzymes, and histopathological analysis results. The nanoemulsion forms of both ACSE and PSCE provided significant increases in antioxidant enzymes, reducing inflammatory parameters, compared to other groups, where liver functions were decreased with values close to those of the control group. In conclusion, both nanoemulsions, ACSE and PSCE, provided a new avenue as therapeutic approaches for liver diseases, and further studies are encouraged to obtain maximum efficiency of treatment via the combination of both extracts.

9.
Life Sci ; 317: 121460, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36716925

RESUMO

AIMS: Chronic kidney disease (CKD) is a growing fatal health problem worldwide associated with vascular calcification. Therapeutic approaches are limited with higher costs and poor outcomes. Adenine supplementation is one of the most relevant CKD models to human. Insufficient Nitric Oxide (NO)/ cyclic Guanosine Monophosphate (cGMP) signaling plays a key role in rapid development of renal fibrosis. Natural products display proven protection against CKD. Current study therefore explored isoliquiritigenin, a bioflavonoid extracted from licorice roots, potential as a natural activator for soluble Guanylate Cyclase (sGC) in a CKD rat model. MATERIALS AND METHODS: 60 male Wistar rats were grouped into Control group (n = 10) and the remaining rats received adenine (200 mg/kg, p.o) for 2 wk to induce CKD. They were equally sub-grouped into: Adenine untreated group and 4 groups orally treated by isoliquiritigenin low or high dose (20 or 40 mg/kg) with/without a selective sGC inhibitor, ODQ (1-H(1,2,4)oxadiazolo(4,3-a)-quinoxalin-1-one, 2 mg/kg, i.p) for 8 wk. KEY FINDINGS: Long-term treatment with isoliquiritigenin dose-dependently and effectively amended adenine-induced chronic renal and endothelial dysfunction. It not only alleviated renal fibrosis and apoptosis markers but also aortic calcification. Additionally, this chalcone neutralized renal inflammatory response and oxidative stress. Isoliquiritigenin beneficial effects were associated with up-regulation of serum NO, renal and aortic sGC, cGMP and its dependent protein kinase (PKG). However, co-treatment with ODQ antagonized isoliquiritigenin therapeutic impact. SIGNIFICANCE: Isoliquiritigenin seems to exert protective effects against CKD and vascular calcification by activating sGC, increasing cGMP and its downstream PKG.


Assuntos
Chalconas , Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Ratos , Masculino , Animais , Guanilil Ciclase Solúvel , Guanilato Ciclase , Ratos Wistar , Óxido Nítrico/metabolismo , Fibrose , GMP Cíclico/metabolismo
10.
Int Immunopharmacol ; 125(Pt A): 111180, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37939515

RESUMO

BACKGROUND: The programmed death-ligand 1 (PD-L1/CD274) gene plays a key function in suppressing anti-tumor immunity through binding to its receptor PD-1 on stimulated T lymphocytes. However, robust associations among diverse populations and lung susceptibility remain unclear. The tentative purpose of this research is to investigate whether PD-L1/CD274 polymorphisms modulate susceptibility to lung carcinoma using totalitarian techniques, including genetic analysis, and sophisticated bioinformatic methods. METHODS: PD-L1/CD274 (rs822336, rs2297136, and rs4143815) variants were genotyped in 126 lung carcinoma cases and 117 healthy controls using tetra-primer ARMS-PCR. Logistic regression and bioinformatics analyses assessed genetic associations. RESULTS: The rs2297136 GA genotype significantly increased lung cancer risk by 3.7-fold versus GG genotype (OR 3.69, 95 % CI 1.39-9.81, p = 0.016), with the minor A allele also increasing risk (OR 1.47, p = 0.044). In contrast, the rs4143815 CC genotype was associated with 70 % decreased cancer risk versus GG (OR 0.30, 95 % CI 0.11-0.87, p = 0.012), although the minor C allele itself was not significant. The rs822336 variant showed no association. Haplotype and multivariate analyses supported these findings. In silico predictions suggested functional impacts on PD-L1 expression and activity. CONCLUSIONS: This study identified novel associations between PD-L1/CD274 polymorphisms and susceptibility to lung cancer in Egyptians. The rs2297136 variant increased risk while the rs4143815 variant conferred protection, highlighting the PD-1/PD-L1 axis as a potential biomarker and therapeutic target in lung oncogenesis. Replication in larger cohorts and functional studies are warranted.


Assuntos
Carcinoma , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/genética , Pulmão/patologia
11.
J Food Biochem ; 46(1): e14017, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34816451

RESUMO

Coffee is among the most commonly consumed beverage all over the world. Studies have increasingly suggested caffeine and coffee as effective therapeutic interventions against Alzheimer's disease (AD). We have therefore utilized the aluminum chloride rat model for AD to compare the influence of moderately caffeinated (Arabian) and decaffeinated (Date palm seed) coffee on cognitive impairment and pathological events in AD. AD rats given Arabian or Date palm seed coffee were protected against memory impairment and had lower serum levels of the abnormal protein (amyloid-beta; Aß1-42), the central pathogenic contributor to AD, and transforming growth factor-beta (TGF-ß). Interestingly, Date palm seed (decaffeinated) coffee seems to provide more pronounced protection against AD than Arabian (moderately caffeinated) coffee as evidenced by the greater decrease in serum Aß levels. These results suggest a surprising therapeutic potential of moderate caffeine intake in Arabian coffee to ameliorate AD through decreasing serum Aß levels. However, Date palm seed (decaffeinated) coffee, rich in flavonoids, appears to provide a better AD-modifying ability through a direct reduction of Aß production. PRACTICAL APPLICATIONS: Consumption of moderately caffeinated Arabian coffee attenuated AD-induced cognitive impairment via its anti-amyloidogenic potential, decreasing Aß levels. Moreover, intake of decaffeinated Date seed extract, rich in flavonoids, exerted a superior anti-AD potential through a direct reduction of Aß production. Both of them were also safe and maintained hepatic and renal functions in a rat model of AlCl3 -induced AD. Further clinical studies are warranted to confirm current results and to recommend the regular drinking of Arabian coffee or Date seed extract as a protective approach to delay AD progression in vulnerable individuals or in early disease stages.


Assuntos
Doença de Alzheimer , Phoeniceae , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Animais , Café/metabolismo , Masculino , Extratos Vegetais/farmacologia , Ratos
12.
Antioxidants (Basel) ; 10(8)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34439442

RESUMO

Cyclosporine A's (CsA) immunosuppressive effect makes it an ideal drug for organ transplantation. However, CsA's uses are restricted due to its side effects. We investigated the effects of avocado seed (AvS) powder on CsA-induced nephrotoxicity and immunosuppression in rats. The injection of CsA (5 mg/kg, subcutaneously, for 10 days) increased serum levels of creatinine, uric acid, and urea, and the renal levels of the malondialdehyde. It decreased creatinine clearance and the renal activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and Na+/K+ ATPase. The administration of CsA also significantly downregulated the renal expression of interferon-gamma, tumor necrosis factor-alpha, interleukin 1 beta, monocyte chemotactic protein 1, intercellular adhesion molecule-1, and vascular cell adhesion molecule 1 genes, and increased renal DNA damage. Histopathological examination confirmed the biochemical and molecular alterations that accompanied CsA nephrotoxicity. All CsA-induced deleterious effects, except immunosuppression, were ameliorated by feeding rats on a basal diet supplemented with 5% AvS powder for 4 weeks. Importantly, AvS also maximized CsA's immunosuppressive effect. These findings suggest a potential ameliorative effect of AvS on CsA-induced nephrotoxicity, and AvS enhances CsA's immunosuppressive effect. Therefore, AvS might be used in combination with CsA in transplantation treatment to relieve the CsA-induced nephrotoxicity.

13.
J Egypt Natl Canc Inst ; 32(1): 33, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32743788

RESUMO

BACKGROUND: Absolute monocyte count (AMC) correlates with survival outcomes in various hematologic malignancies. However, its role in myeloid malignancies including AML needs to be highlighted. So, this prospective cohort study aimed to assess the effect of AMC on the treatment outcome and survival in a 56 adult de novo AML patients with monocytic differentiation, admitted to the Clinical Hematology Unit, Internal Medicine Department, in a tertiary referral hospital in Egypt, from July 2016 to June 2019. RESULTS: The initial AMC was measured either by manual differential or the hematology automatic analyzer Sysmex XN-2000 and patients were classified by using receiver operating characteristic curve into two groups monocytopenic (≤ 4 × 109/L) and non-monocytopenic (> 4 × 109/L) group; including 24 (42.9%) and 32 (57.1%) patients, respectively. After a median follow up period of 7.7 (range 0.5-33.2) months, the monocytopenic group was associated with a significantly higher CR rate (P = 0.019), with a lower death as well as relapse and early relapse rates (P = 0.011, 0.033, and 0.002, respectively). Moreover, low initial AMC along with intensive induction were independently associated with complete response to induction chemotherapy with HR, 5.04 [1.37-18.58], P = 0.015, and 5.67 [1.48-21.71], P = 0.011, respectively by using the multivariate logistic regression model. Regarding survival, the monocytopenic group was associated with a better 3-year disease-free survival rate (P = 0.011) in univariate Cox regression only but did not reach significance in the multivariate model and did not affect the overall survival as well. CONCLUSION: Initial AMC was found to be an independent prognostic immune biomarker for treatment response in AML patients with monocytic differentiation. However, it did not appear as an independent predictor of survival in a multivariate analysis.


Assuntos
Leucemia Mieloide Aguda , Monócitos , Adulto , Biomarcadores , Egito , Humanos , Leucemia Mieloide Aguda/diagnóstico , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
14.
Int J Biol Macromol ; 155: 861-867, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31786303

RESUMO

Fungal chitosan (FCt) from Amylomyces rouxii, with 88.7% deacetylation degree and 112.4 kDa molecular weight, was utilized for nanoparticles (NPs) formation via ionic gelation. FCt-NPs were employed as carriers for curcumin (CUR) to augment its availability and anticancer bioactivity. The synthesis of CUR/FCt-NPs composite was succeeded as evidenced from their FTIR spectra. The scanning micrographs of synthesized CUR/FCt-NPs indicated their spherical shapes and well-distribution; they had average diameters of 115 ± 21 nm and positive zeta potentials of +33.8 mV. The NPs loading capacity for CUR was 21.6% and the encapsulation efficiency reached 83.8%. The CUR was vastly released in the beginning 5 h then gradually released up to 90 h, with higher release in pH 5.2 than in pH 7.0. The treatment of cancer cells, HCT-116 and A-549, with CUR/FCt NPs lead to time-dependent decrement of cells' viability; the dead cells were 67.6% from HCT-116 and 73.8% from A-546 after 96 h of exposure. Fluorescent imaging indicated that most cancer cells entered the apoptosis phase after treatment with 150 µM of CUR/FCt-NPs for 72 h. The efficiency of FCt-NPs was proved as carriers for loading CUR and augmenting its anticancer activity toward human cancer cells, using these natural and biosafe agents.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Quitosana/química , Curcumina/farmacologia , Portadores de Fármacos/química , Mucorales/química , Células A549 , Células HCT116 , Humanos , Nanopartículas/química , Neoplasias/tratamento farmacológico
15.
Saudi J Biol Sci ; 26(7): 1875-1881, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31762670

RESUMO

Cadmium is among the toxic and hazardous metal widely dispersed in the environment in high levels. Current studies have provided new insights into antioxidant properties of bioflavonoid which have emerged as probable therapeutic and nutraceutical agents. The present study is geared to investigate the possible role of Cymbopogon schoenanthus (L.) Spreng. (or Ethkher) on heavy metal cadmium (Cd) induced oxidative stress in mice. Mice were randomly divided into four groups and treated for 15 days as follows: group 1: normal control-treated (saline); group 2: Ethkher leaves extract-treated (100 mg/kg); group 3: cadmium chloride (CdCl2) treated; group 4: CdCl2 plus Ethkher leaves extract. The results showed a significant reduction in hemoglobin, RBC and hematocrit in cadmium-treated mice as compared to control. Exposure to Cd caused a significant increase in the number of white blood cells (P < 0.05) indicating the occurrence of systemic inflammation. The results of this study also revealed that the mice intoxicated with Cd showed a significant increase in bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGTP) activities. Cd intoxication leads to suppression in humoral immunity. However, pretreatment with Ethkher extract reversed almost all the abnormalities in the blood parameters showing noteworthy protection against cadmium induced toxicity in mice. The outcome of the present study revealed that the Ethkher possessed significant immunomodulatory activity and had a preventive effect on the hematological alterations in Cd intoxicated mice.

16.
Int J Biol Macromol ; 141: 511-516, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499111

RESUMO

Fungal chitosan (ACT) extraction from Amylomyces rouxii, its transforming into nano-form, loading with fluconazole (Flu) and evaluation of synthesized nanoconjugates against drug-resistant (DR) Candida spp., were investigated. The produced ACT was characterized with 112.4 kDa molecular weight and 88.7% deacetylation degree. Synthesis of chitosan nanoparticles (NACT), and loading them with Flu were succeeded, using ionic gelation protocol, to generate stable Flu/NACT nanoconjugate' particles with mean size of 82 nm and zeta potential of +3.36 mV. The NACT entrapment efficiency was 78.7% and the drug loading capacity was 60.2%. Flu slowly released from NACT during the first 5 h, then release dramatically increased to the maximum (94.8%) after 12 h. The infra-red spectrum of Flu/NACT nanoconjugates confirmed the strong cross-linkage between their molecules. The antimycotic activity of NACT and Flu/NACT was proved against DR strains of C. albicans (2 strains), C. parapsilosis and C. glabrata, using qualitative and quantitative assays; Flu/NACT exhibited significant powerful activity, which was confirmed via observations with scanning microscopy. Finished cotton textiles with Flu/NACT had augmented potentiality for inhibiting challenged DR Candida spp., using in vitro assay. Accordingly, the synthesis and application of Flu/NACT nanoconjugates was astoundingly recommended for controlling DR Candida spp.


Assuntos
Candida/crescimento & desenvolvimento , Quitosana , Farmacorresistência Fúngica/efeitos dos fármacos , Fluconazol , Polissacarídeos Fúngicos , Mucorales/química , Quitosana/química , Quitosana/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Fluconazol/química , Fluconazol/farmacologia , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia
17.
Saudi J Biol Sci ; 22(3): 322-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25972754

RESUMO

The phytochemical, antioxidant and mineral composition of hydroalcoholic extract of leaves of Cichorium intybus L., was determined. The leaves were found to possess comparatively higher values of total flavonoids, total phenolic acids. The phytochemical screening confirmed the presence of tannins, saponins, flavonoids, in the leaves of the plant. The leaf extract was found to show comparatively low value of IC50 for 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition. The IC50 value of chicory leaves extract was found to be 67.2 ± 2.6 µg/ml. The extracts were found to contain high amount of mineral elements especially Mg and Zn. Due to good phytochemical and antioxidant composition, C. intybus L., leaves would be an important candidate in pharmaceutical formulations and play an important role in improving the human health by participating in the antioxidant defense system against free radical generation.

18.
Redox Rep ; 19(1): 26-33, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24191932

RESUMO

OBJECTIVE: Acetaminophen (APAP) is a substance that harms human health by stimulating free radical production. This study investigated the ability of Trifolium alexandrinum root (TAR) extract to reduce the hepatotoxicity induced by APAP in rats. METHODS: Animals were classified into four groups and treated for 6 weeks. Group 1: normal control-treated (saline); Group 2: TAR extract-treated (100 mg/kg); Group 3: APAP-treated; Group 4: APAP plus TAR extract. RESULTS: APAP significantly elevated AST (aspartate amino transferase), ALT (amino alanine transferase), ALP (alkaline phosphatase), GGTP (gamma glutamyl transpeptidase), bilirubin, and malondialdehyde with a significant decrease in glutathione, superoxide dismutase, glutathione peroxidase, catalase, and glutathione S-transferase compared with the control group. Administration of TAR extract combined with APAP improved the liver damage induced by APAP. Histopathological evidence, together with observed DNA fragmentation, supported the detrimental effect of APAP and the ameliorating effect of TAR extract on liver toxicity. CONCLUSION: TAR extract has beneficial properties and can reduce the liver damage and toxicity induced by APAP. DISCUSSION: Free radical mediated processes have been implicated in the pathogenesis of many diseases. The protective effect of TAR root extract on APAP-induced hepatotoxicity in rats appears to be related to inhibition of lipid peroxidation and enhancement of antioxidant enzyme levels, in addition to a free radical scavenging action.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Trifolium , Acetaminofen/farmacocinética , Animais , Benzoquinonas/metabolismo , Biotransformação , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fragmentação do DNA/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Iminas/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Testes de Função Hepática , Metanol , Raízes de Plantas/química , Ratos , Solventes , Água
19.
Food Chem Toxicol ; 72: 138-46, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25010453

RESUMO

The current study was carried out to elucidate the modulating effect of chicory (Cichorium intybus L.) fruit extract (CFR) against 4-tert-OP induced oxidative stress and hepatotoxicity in male rats. Rats were divided into four groups and treated for 8 weeks as follow: group 1: normal control-treated (saline); group 2: chicory fruit extract-treated (100 mg/kg); group 3: 4-tert-OP treated; group 4: 4-tert-OP plus chicory fruit extract. The obtained results revealed that rats which received 4-tert-OP showed a significant increase in liver TBARS and bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGTP) activities. While a significant decrease in the levels of GSH, SOD, catalase recorded. On the other hand, CFR extract succeeded to modulate these observed abnormalities resulting from 4-tert-OP as indicated by the reduction of TBARS and the pronounced improvement of the investigated biochemical and antioxidant parameters. Histopathological evidence, together with observed PCNA and DNA fragmentation, supported the detrimental effect of 4-tert-OP and the ameliorating effect of CFR extract on liver toxicity. So, it could be concluded that chicory has a promising role and it worth to be considered as a natural substance for ameliorating the oxidative stress and hepatic injury induced by 4-tert-OP compound.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Cichorium intybus/química , Frutas/química , Estresse Oxidativo/efeitos dos fármacos , Fenóis/efeitos adversos , Extratos Vegetais/farmacologia , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/metabolismo , Bilirrubina/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Compostos Fitoquímicos/farmacologia , Ratos , Ratos Sprague-Dawley , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , gama-Glutamiltransferase/metabolismo
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