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1.
Fish Physiol Biochem ; 47(2): 293-311, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33394283

RESUMEN

This study reports the antioxidant property and molecular mechanism of a tryptophan-tagged peptide derived from a teleost fish Channa striatus of serine threonine-protein kinase (STPK). The peptide was tagged with tryptophan to enhance the antioxidant property of STPK and named as IW13. The antioxidant activity of IW13 peptide was investigated using in vitro methods such as DPPH, ABTS, superoxide anion radical scavenging and hydrogen peroxide scavenging assay. Furthermore, to investigate the toxicity and dose response of IW13 peptide on antioxidant defence in vitro, L6 myotubes were induced with generic oxidative stress due to exposure of hydrogen peroxide (H2O2). IW13 peptide exposure was found to be non-cytotoxic to L6 cells in the tested concentration (10, 20, 30, 40 and 50 µM). Also, the pre-treatment of IW13 peptide decreased the lipid peroxidation level and increased glutathione enzyme activity. IW13 peptide treatment upregulated the antioxidant enzyme genes: GPx (glutathione peroxidase), GST (glutathione S transferase) and GCS (glutamine cysteine synthase), in vitro in L6 myotubes and in vivo in zebrafish larvae against the H2O2-induced oxidative stress. The results demonstrated that IW13 renders protection against the H2O2-induced oxidative stress through a cellular antioxidant defence mechanism by upregulating the gene expression, thus enhancing the antioxidant activity in the cellular or organismal level. The findings exhibited that the tryptophan-tagged IW13 peptide from STPK of C. striatus could be a promising candidate for the treatment of oxidative stress-associated diseases.

2.
J Obstet Gynaecol ; : 1-7, 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33475035

RESUMEN

The study aimed to screen for PIK3CA gene mutations among Saudi women with Ovarian Cancer. The study included 298 Saudi women with epithelial ovarian cancers (EOC). DNA sequence analysis was employed to screen for the mutations. DNA sequence analysis of a coding region of exon 9 and 20 of PIK3CA gene revealed mutations in 37/298 (12.4%) EOC patients. About 21/37(56.8%) somatic mutations were identified in exons 9, and 16/37(43.2%) in exon 20. All analysed mutations were missense mutations, the frequencies of which varied from 2.7% to 43.2%. PIK3CA mutation was found to be significantly associated with age (p = .023), grade (p = .001) and histological types (p = .032). Only 6.6% of serous carcinomas and 3.8% of endometrioid had PIK3CA mutation. The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management. Impact statement What is already known on this subject? The detailed molecular and genetic phenomenon underlying the progression of these tumours is still unclear. Recently, the pathogenesis of ovarian cancer has been attributed to mutations of PIK3CA. What do the results of this study add? Mutation in the PIK3CA gene leads to altered PI3K/AKT signalling pathways responsible for the progression of the epithelial ovarian cancer. What are the implications of these findings for clinical practice and/or further research? The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management.

3.
Chemosphere ; 267: 129243, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33338721

RESUMEN

Because of the abundance of transition metals, their enhanced electrochemical/chemical efficiency on par with the benchmark catalysts, long-term stability, etc., the expansion of transition metal/metal oxide-based electrocatalysts for oxygen evolution, urea oxidation reactions and 4-nitrophenol reduction becomes indispensable. In particular, the abundant availability along with improved electrochemical performance is crucial for fuel cell applications when it comes to large scale commercialization. In this work, we report the synthesis of a trimetallic metal-organic framework based on Ni, Co and Zn using BTC as a linker and the preparation of its metal oxide - carbon composites at different temperatures, 600, 700 and 800 °C (TM-MOF-600, TM-MOF-700, and TM-MOF-800) by carbonization under an inert atmosphere. The PXRD pattern of TM-MOF complemented well with the simulated XRD patterns of Co-Ni-BTC MOF as well as Zn-BTC MOF, whereas the PXRD pattern of the carbonized samples indicated the presence of three types of metal oxides i.e., CoO, NiO, and ZnO. TEM indicated spherical morphology of TM-MOF, upon calcination, an irregular agglomeration occurred and the average particle size was found to be 60-110 nm. The as-prepared TM-MOF and its carbon composites were tested for their electrocatalytic as well as catalytic activities towards oxygen evolution, urea oxidation and 4-nitrophenol reduction reactions. Electrochemical results indicate the better performance of TM-MOF-800 in both OER and UOR reactions with an onset potential of 1.66 V (OER) and 1.37 V (UOR) at a current density of 10 mA cm-2. The long-term stability of these catalysts under alkaline conditions indicates excellent stability. Besides, the urea electrolyzed products were analyzed by gas chromatography to get clear insights on the formed products. Catalytic reduction of 4-nitrophenol in the presence of excess NaBH4 showed excellent conversion to 4-amino phenol in short duration.


Asunto(s)
Carbono , Urea , Catálisis , Metales , Nitrofenoles
4.
Chemosphere ; 267: 129245, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33321274

RESUMEN

Phenolic compounds bisphenol A (BPA) and 4-nitrophenol (4-NP) are the prime water contaminants. As reported, these compounds are some of the highly hazardous ones to the human and living species. In this study, T-ZnO-rGO-PEI composite was synthesized employing hydrothermal method and the obtained composite samples were systematically characterized by FTIR, XPS, FE-SEM and HR-TEM studies. The FTIR, XPS analysis confirmed the successful surface modification of T-ZnO-rGO-PEI composite. The FE-SEM morphology confirmed the formation of ZnO (arm length about 2.5 µm) tetrapod structured in synthesized T-ZnO-rGO-PEI composite. The thickness of formed ZnO arm (0.44 µm) was increased after the polymer coating which confirmed the successful surface modification by PEI polymer. The HR-TEM images confirm the uniform coating of PEI polymer on T-ZnO-rGO surface. The catalytic activity and adsorption capacity of the synthesized T-ZnO-rGO-PEI composite was successfully explored using 4-nitrophenol and bisphenol-A as model pollutants .T-ZnO-rGO-PEI composite and found that 4-NP reduction reaction was completed within 10 min with the rate of 0.224 min-1. The BPA adsorption over T-ZnO-rGO-PEI exhibited high adsorption rate of 0.0210 min-1. In addition, the detailed 4-NP reduction and BPA adsorption mechanism was demonstrated. Hence the synthesized T-ZnO-rGO-PEI composite is a promising catalyst for the removal of micropollutants in aqueous medium.


Asunto(s)
Grafito , Óxido de Zinc , Adsorción , Catálisis , Color , Humanos
5.
Int J Mol Sci ; 21(23)2020 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-33291656

RESUMEN

Phorbol 12-myristate 13-acetate (PMA) is a potent tumor promoter and highly inflammatory in nature. Here, we investigated the toxic effects of PMA on different model system. PMA (10 µg) caused chromosomal aberrations on the Allium cepa root tip and induced mitotic dysfunction. Similarly, PMA caused embryonic and larval deformities and a plummeted survivability rate on zebrafish embryo in a dose-dependent manner. Persistently, PMA treatment on immortalized human keratinocyte human keratinocyte (HaCaT) cells caused massive inflammatory rush at 4 h and a drop in cell survivability at 24 h. Concomitantly, we replicated a cutaneous inflammation similar to human psoriasis induced by PMA. Herein, we used tangeretin (TAN), as an antagonist to counteract the inflammatory response. Results from an in vivo experiment indicated that TAN (10 and 30 mg/kg) significantly inhibited PMA stimulated epidermal hyperplasia and intra-epidermal neutrophilic abscesses. In addition, its treatment effectively neutralized PMA induced elevated reactive oxygen species (ROS) generation on in vitro and in vivo systems, promoting antioxidant response. The association of hypoxia-inducible factor 1-alpha (HIF-1α)-nuclear factor kappa-light-chain-enhancer of activated b cells (NF-κB) crosstalk triggered by PMA enhanced PKCα-ERK1/2-NF-κB pathway; its activation was also significantly counteracted after TAN treatment. Conclusively, we demonstrated TAN inhibited the nuclear translocation of HIF-1α and NF-κB p65. Collectively, TAN treatment ameliorated PMA incited malignant inflammatory response by remodeling the cutaneous microenvironment.

6.
Biosci Rep ; 2020 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-33252120

RESUMEN

Leishmaniasis is a group of infectious and non-contagious severe parasitic diseases, caused by protozoans of the Leishmania genus. Natural products characterize a rich source of prospective chemical entities for the development of new effective drugs for neglected diseases. Scientific evaluation of medicinal plants has made it possible to use some metabolites from flavonoids and polyphenols compounds for the treatment of parasitic diseases. Therefore, we aimed in this study to evaluate the protective effect of Silver nanoparticles (Ag-NPs) biosynthesized using Fig and Olive extracts (NFO) against Cutaneous leishmaniasis in female Balb/c mice. A total of 70 mice were used and divided into seven groups. Treatment was initiated when local lesions were apparent, we found Fig and Olive extracts were found to be a good source for the synthesis of (Ag-NPs), their formation was confirmed by color change and stability in solution. Nanoparticles biosynthesized using Fig and Olive extracts induced a reduction in the average size of cutaneous leishmaniasis lesions compared with the untreated mice. Moreover, nanoparticles treatment decreased oxidative stress (LPO, NO), down regulation gene expression levels (TNF-α, IL-1ß and BAX) and this antileishmanial activity of nanoparticles was associated with enhanced antioxidant enzyme activities. In addition, histopathological evaluation proved the antileishmanial activity of nanoparticles compared to the positive control. Therefore, we aimed in this study to evaluate the protective effect of silver nanoparticles biosynthesized using Fig and Olive extracts against cutaneous lesions induced by Leishmania major infection through their anti-inflammatory, antioxidant activities and faster clinical efficacy than standard pentavalent antimonial treatment.

7.
Sci Total Environ ; 723: 137969, 2020 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-32392679

RESUMEN

Environmental and occupational exposure to heavy metals, including cadmium (Cd), is associated with extremely adverse impacts to living systems. Antioxidant agents are suggested to eliminate Cd intoxication. In this paper, we investigated the potential neuroprotective effect of protocatechuic acid (PCA) against Cd-induced neuronal damage in rats. Adult male Wistar rats were randomly divided into control, PCA (100 mg/kg)-treated, CdCl2 (6.5 mg/kg)-treated, and PCA and Cd treatment groups. Pre-treatment with PCA significantly reduced Cd concentrations and increased cortical acetylcholinesterase activity and brain derived neurotrophic factor. Additionally, PCA also prevented CdCl2-induced oxidative stress in the cortical tissue by preventing lipid peroxidation and the formation of nitric oxide (NO), and significantly enhancing antioxidant enzymes. Molecularly, PCA significantly up-regulated the antioxidant gene expression (Sod2, Cat, Gpx1, and Gsr) that was down-regulated by Cd. It should be noted that this effect was achieved by targeting the nuclear-related factor 2 (Nfe2l2) mRNA expression. PCA also prevented the Cd-induced inflammation by reducing the pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß. Moreover, PCA supplementation relieved the Cd-induced neuronal death by increasing Bcl-2 and decreasing Bax and Cas-3 levels in the cortical tissue. The improvement of the cortical tissue histopathology by PCA confirmed the biochemical and molecular data. Collectively, our findings indicate that PCA can counteract Cd-induced cortical toxicity by enhancing the antioxidant defense system and suppressing inflammation and apoptosis.


Asunto(s)
Cadmio , Estrés Oxidativo , Animales , Antioxidantes , Apoptosis , Hidroxibenzoatos , Inflamación , Masculino , Ratas , Ratas Wistar
8.
Biomed Res Int ; 2020: 9035341, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32280706

RESUMEN

The present study was undertaken to confirm the genetic identity of Clostridium perfringens isolates from domestic livestock in Saudi Arabia and to characterize the genes encoding to alpha, beta, epsilon, and iota (α-, ß-, ε-, and ι-) toxins. C. perfringens were confirmed in 104 out of 136 isolates on multiplex polymerase chain reaction using specific primers amplifying genes related to toxins produced by C. perfringens. Genes encoding α-toxins were detected in 104 samples. Of the isolates, 80.8% were diagnosed as type A, 15.4% as type D, 2.9% as type C, and 0.96% as type B. None of the isolates has genes encoding iota (ι-) toxin. All isolates investigated yielded enterotoxin (cpe) products and none yielded ß2 (cpb2-toxin) or NetB products. PLC gene sequences encoding α-toxin showed >96.7% similarity. Isolates which had α-toxins as well as enterotoxin (cpe) are regarded as type F. Phylogenetic analysis using maximum likelihood analysis yielded two clades, and the majority of the isolates were in one group while only two isolates clustered on the second clade. Within the Kingdom of Saudi Arabia strains, 54 variable positions and 23 polymorphic amino acids were noticed. Isolates with ε- and ß-toxins were variable and were found to be close to those published for C. perfringens. ETX gene sequences encoding ε-toxins were found to be related to CPE sequences.

9.
BMC Complement Altern Med ; 19(1): 3, 2019 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-30606163

RESUMEN

BACKGROUND: Considerable morbidity, mortality, and economic loss result from schistosomiasis infection. Deposition of Schistosoma eggs in the hepatic portal vein is considered as the main causative agent for the development of liver fibrosis and subsequent liver cirrhosis. Probiotics are exogenous and beneficial microorganisms to living hosts against the harmful effect of many parasites. Strong evidence suggests the importance of probiotics in the control strategy of helminth. The ultimate goal of this study is to evaluate the protective effect of probiotics and yogurt on Schistosoma mansoni-induced oxidative stress and hepatic fibrosis in mice. METHODS: Mice were infected by tail immersion of schistosomal cercariae followed by an oral treatment with either probiotics or yogurt for one week before infection and immediately post-infection. Mice were scarified on day 56 following infection with S. mansoni and liver sample were obtained. RESULTS: We showed that oral administration of probiotics or yogurt revealed a significant reduction in worm number, egg load, and granuloma size in liver tissue, which is mainly assigned to the decreased expression level of matrix metalloproteinases 9 (MMP-9) in liver tissue. A significant reduction in the oxidative stress markers-induced by S. mansoni infection including lipid peroxidation and nitrite/nitrate was also detected. The level of some antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) and reduced glutathione was greatly enhanced. Furthermore, treatment with probiotics or yogurt inhibited apoptosis in hepatic tissue, which is mainly assigned to the decreased expression level of caspases-3 in liver tissue. CONCLUSION: Our findings represent the promising anti-schistosomal activities of probiotics and yogurt.


Asunto(s)
Interacciones Huésped-Parásitos/efectos de los fármacos , Cirrosis Hepática/metabolismo , Estrés Oxidativo/efectos de los fármacos , Probióticos/farmacología , Esquistosomiasis mansoni/metabolismo , Yogur , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/parasitología , Hígado/patología , Cirrosis Hepática/parasitología , Masculino , Ratones , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/parasitología
10.
Altern Ther Health Med ; 25(3): 17-24, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-28646810

RESUMEN

Context: Breast cancer is a leading cause of cancer fatalities among women worldwide. Of the more than 80% of patients who receive adjuvant chemotherapy, approximately 40% relapse. The majority of these patients die of disseminated metastatic disease, which emphasizes the need for new therapeutic strategies. Objective: The study intended to investigate the anticancer effects of oleuropein (OL) and doxorubicin (DOX) individually and in combination on breast tumor xenografts and also to evaluate the molecular pathways involved. Design: The research team designed in vivo (animal) and in vitro (cell culture) studies. Setting: The study was performed in the College of Science of King Saud University in the University Center for Women Students (Riyadh, Saudi Arabia). Animals: The study involved 40 female, nude mice (BALB/c OlaHsd-foxn1). Intervention: The mice were injected subcutaneously with MDA-MB-231 human breast cancer cells. After the growth of tumors, the animals were randomly divided into 4 groups to receive intraperitoneal injections: (1) group 1 (control group)-dimethyl sulfoxide, (2) group 2 (intervention group)-50 mg/kg of OL, (3) group 3 (intervention group)-2.5 mg/kg of DOX, and (4) group 4 (intervention group)-1.5 mg/kg of DOX, immediately followed by 50 mg/kg of OL. The OL was extracted from Manzanillo olive trees (Olea europaea) grown in Tabouk, Saudi Arabia. Outcome Measures: The measures included the isolation and primary culture of the tumor xenografts, apoptosis analysis by annexin V, cellular lysate preparation, and immunoblotting. Results: The volume of the tumor increased aggressively, reaching 173 mm3 in the control animals in a time-dependent manner. On the other hand, a sharp drop, to 48.7 mm3, in the volume of the tumor was observed with the 2 drugs combined, a more than 3-fold decrease. The effect was mediated through the induction of apoptosis via the mitochondrial pathway. The combined treatment downregulated the antiapoptosis and proproliferation protein, nuclear factor-kappa Β, and its main oncogenic target cyclin D1. Furthermore, it inhibited the expression of BCL-2 and survivin. This inhibition could explain the cooperative suppression of the proliferation of breast tumor xenografts and the induction of apoptosis by the combined effect of the compounds used. Conclusions: The key findings clearly indicate the synergistic efficacy of DOX with natural and nontoxic OL against breast tumor xenografts.


Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/uso terapéutico , Iridoides/uso terapéutico , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Recurrencia Local de Neoplasia
11.
Biosci Rep ; 38(6)2018 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-30291211

RESUMEN

Cadmium (Cd) is a common environmental toxicant that has harmful effects on plants, animals, and humans. The present study evaluated the protective effects of Fragaria ananassa methanolic extract (SME) on cadmium chloride (CdCl2)-induced neuronal toxicity in rats. Male albino rats were intraperitoneally (i.p) injected with CdCl2 (6.5 mg/kg) for 5 days with or without the SME (250 mg/kg). We measured the levels of Cd, lipid peroxidation (LPO), nitric oxide, glutathione (GSH), and oxidative enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase, and glutathione reductase (GR) in the whole brain homogenate. Compared with the control group, the Cd-intoxicated group showed a marked increase in the brain levels of Cd, LPO, and nitric oxide and a decrease in the levels of GSH and all tested antioxidant enzymes. Compared with Cd-intoxicated rats, the rats pretreated with SME showed restoration of oxidative balance in the brain tissue. While the expression of brain SOD2, CAT, glutathione peroxidase 1, and GR was down-regulated in the Cd-treated group, the expression of these enzymes was up-regulated in rats pretreated with SME. In addition, administration of SME before CdCl2 increased the Bcl-2 expression, but significantly decreased the expression of Bax. Immunohistochemical analysis showed that compared with Cd-intoxicated rats, rats pretreated with SME showed a decrease in the protein expression of tumor necrosis factor α (TNF-α). Our findings indicate that SME protects the brain tissue from Cd-induced neuronal toxicity by improving the antioxidant system and increasing antiapoptotic and anti-inflammatory activities.


Asunto(s)
Cloruro de Cadmio/toxicidad , Fragaria/química , Neuronas/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Animales , Antioxidantes/administración & dosificación , Antioxidantes/química , Apoptosis/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Peroxidación de Lípido/efectos de los fármacos , Neuronas/patología , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/química , Ratas , Factor de Necrosis Tumoral alfa/genética
12.
Biosci Rep ; 38(6)2018 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-30291217

RESUMEN

The present study was designed to investigate the use of specific biomarkers, such as albumin, serum total protein, aspartate amino transferase (AST), globulin, alanine amino transferase (ALT), serum cortisol and alkaline phosphatase (ALP), as predictive tools for sarcoptic mange in rabbits. A total of 40 naturally infested rabbits were equally divided into four groups.Thirty infested rabbits were administered with three different treatments (propolis,ivermectin, and propolis with ivermectin) and were compared to10 infested un-treated rabbits. The impact of treatment was assessed via microscopic examination of skin scrapings, clinical signs, and blood measurements relating to the liver. The present study demonstrated that topical application of 10% propolis ointment resulted in complete recovery from clinical signs and complete absence of mites based on microscopic examination after 10-15 days of treatment. Moreover, AST, ALP, ALT, and cortisol were determined to be acceptable biomarkers to track the response of diseased rabbits to the therapeutic use of propolis.


Asunto(s)
Apiterapia , Própolis/uso terapéutico , Conejos/parasitología , Escabiosis/veterinaria , Animales , Apiterapia/métodos , Biomarcadores/análisis , Femenino , Pronóstico , Escabiosis/diagnóstico , Escabiosis/patología , Escabiosis/terapia , Piel/parasitología , Piel/patología
13.
BMC Complement Altern Med ; 18(1): 135, 2018 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-29703259

RESUMEN

BACKGROUND: Schistosomiasis is an acute and chronic zoonotic parasitic disease caused by trematode worms. The host inflammatory response to schistosome eggs leads to perioval granulomata formation, mainly in the liver and intestine. This study investigated the potential antischistosomal and anti-inflammatory activity of both garlic extract and allicin on liver fibrotic markers in BALB/c mice with schistosomiasis (S. mansoni infection) compared with that of the commonly used drug, praziquantel (PZQ). METHODS: In this study, 140 female BALB/c mice (7-weeks old) were divided into seven groups with 20 mice each. Six groups were infected with S. mansoni cercariae and treated with garlic, allicin, or PZQ. The seventh group was the negative control. Twenty-four hours after the final treatment, the mice were euthanised and perfused for worm recovery. The liver and intestines were harvested for parasitological and histological assessment and to analyse the proinflammatory cytokine mRNA expression. RESULTS: Prophylactic administration of garlic and allicin to the infected mice significantly reduced the worm burden. Serum concentrations of liver fibrosis markers and proinflammatory cytokines were also reduced. PZQ was the most efficacious for reduction in the number of worms. These results are similar to those normally obtained using PZQ. CONCLUSIONS: Crushed garlic homogenate and allicin are potential complementary treatments that may be used with PZQ.


Asunto(s)
Antiinflamatorios/farmacología , Ajo , Praziquantel/farmacología , Esquistosomicidas/farmacología , Ácidos Sulfínicos/farmacología , Animales , Biomarcadores/análisis , Citocinas/análisis , Citocinas/genética , Citocinas/metabolismo , Femenino , Inmunohistoquímica , Hígado/parasitología , Masculino , Ratones , Ratones Endogámicos BALB C , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/parasitología
14.
Biol Trace Elem Res ; 181(2): 378-387, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28567583

RESUMEN

For experiments of cadmium toxicity in animal models, cadmium (II) chloride is often used due to its solubility in water and its ability to produce high concentrations of cadmium at the target site. The present study was designed to investigate the potential inhibitory effect of the Fragaria ananassa fruit extract on cadmium (II) chloride-induced renal toxicity in rats. Tested animals were pretreated with the extract of F. ananassa and injected with cadmium (II) chloride (6.5-mg/kg body weight) for 5 days. Cadmium (II) chloride significantly increased kidney cadmium concentration, kidney weight, lipid peroxidation, and nitric oxide production. Plasma uric acid, urea, and creatinine levels also increased significantly, indicative of kidney dysfunction. These effects were accompanied by significantly decreased levels of nonenzymatic and enzymatic antioxidant molecules (i.e., glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). Moreover, messenger RNA (mRNA) expression of the antiapoptotic protein, Bcl-2, and the antioxidant proteins, superoxide dismutase 2 and glutathione reductase, were downregulated markedly, whereas mRNA expression of tumor necrosis factor-α was upregulated significantly in kidney tissues of cadmium-treated rats. Histology of kidney tissue demonstrated severe, adverse changes that reflected cadmium-induced tissue damage. Pretreatment of rats with the extract of F. ananassa ameliorated all aforementioned cadmium (II) chloride-induced changes. In conclusion, the present study showed acute renal toxicity in rats treated with cadmium (II) chloride. The study also revealed that pretreatment with the extract of F. ananassa could protect the kidney against cadmium (II) chloride-induced acute renal toxicity.


Asunto(s)
Cloruro de Cadmio/antagonistas & inhibidores , Fragaria/química , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Insuficiencia Renal/prevención & control , Animales , Cloruro de Cadmio/toxicidad , Inmunohistoquímica , Masculino , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Sustancias Protectoras/química , Sustancias Protectoras/aislamiento & purificación , Ratas , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/patología
15.
Artículo en Inglés | MEDLINE | ID: mdl-29258248

RESUMEN

Leishmania species are parasites that multiply within phagocytes and cause several clinical diseases characterized by single or multiple ulcerations. One of the complications that can induce tissue damage and the resulting scars is caused by secondary bacterial infections. Studies to find new, effective, and safe oral drugs for treating leishmaniasis are being conducted since several decades, owing to the problems associated with the use of antimonials available. Previously, the antiparasitic and antioxidant properties of Punica granatum (pomegranate, P. granatum) have been reported. Therefore, in the present study, we aimed to investigate the antileishmanial activity of pomegranate aqueous juice in vitro and in female BALB/c mice. A 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in Leishmania major promastigotes and alterations in the antioxidant status, liver function, and skin histological changes in L. major-infected mice orally treated with pomegranate juice alone and in combination with the antibiotic ciprofloxacin, were used to investigate the in vitro and in vivo antileishmanial activity of pomegranate juice, respectively. Oral P. granatum juice treatment significantly reduced the average size of cutaneous leishmaniasis lesions compared with that of the untreated mice. This antileishmanial activity of P. granatum was associated with enhanced antioxidant enzyme activities. Histopathological evaluation proved the antileishmanial activity of P. granatum, but did not reveal changes in the treated animals, compared to the positive control. In conclusion, P. granatum shows high and fast antileishmanial activity probably by boosting the endogenous antioxidant activity.


Asunto(s)
Antioxidantes/farmacología , Jugos de Frutas y Vegetales/análisis , Leishmaniasis Cutánea/fisiopatología , Lythraceae/química , Estrés Oxidativo/efectos de los fármacos , Animales , Femenino , Leishmaniasis Cutánea/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C
16.
Artículo en Inglés | MEDLINE | ID: mdl-28703780

RESUMEN

Bacterial infections of cutaneous leishmaniasis cause skin ulcers on mice, resulting in increased tissue deterioration, and these infections can be controlled with liquid allicin. To isolate and identify the incidences of real secondary bacterial infections in mice, we performed the current study by injecting mice (n = 50) with Leishmania major. L. major infections were initiated by an intramuscular injection of 0.1 mL Roswell Park Memorial Institute (RPMI 1640 media/mouse (107 promastigote/mL)). Scarring appeared 2-6 weeks after injection, and the bacteria were isolated from the skin ulcer tissues. Allicin (50 µL/mL) and ciprofloxacin (5 µg; Cip 5) were used for controlling L. major and bacteria. One hundred samples from skin ulcers of mice were examined, and 200 bacterial colonies were isolated. Forty-eight different genera and species were obtained and identified by Gram staining and physiological and biochemical characterization using identification kits. All samples were positive for secondary bacterial infections. Of the isolates, 79.16% were identified as Gram-negative bacteria, and 28.84% were identified as Gram-positive bacteria; only one yeast species was found. Interestingly, pure allicin liquid at a concentration 50 µL/mL exhibited antibacterial activity against a wide range of Gram-negative and some Gram-positive bacteria, in addition to yeast, and was 71.43% effective. Antimicrobial resistance patterns of all genera and species were determined using 15 different antibiotics. Allicin (50 µL/mL) and Cip 5 were the most effective against L. major and 92.30% of isolated bacteria. Stenotrophomonas maltophilia was the most resistant bacterium to the tested antibiotics with a survival rate of 73.33%, and it exhibited resistance to allicin.


Asunto(s)
Antiinfecciosos/uso terapéutico , Ciprofloxacino/uso terapéutico , Infecciones por Bacterias Gramnegativas , Infecciones por Bacterias Grampositivas , Leishmaniasis Cutánea , Ácidos Sulfínicos/uso terapéutico , Animales , Antiinfecciosos/farmacología , Ciprofloxacino/farmacología , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/etiología , Infecciones por Bacterias Gramnegativas/microbiología , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/aislamiento & purificación , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/etiología , Infecciones por Bacterias Grampositivas/microbiología , Leishmaniasis Cutánea/complicaciones , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/microbiología , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Ácidos Sulfínicos/farmacología , Levaduras/efectos de los fármacos , Levaduras/aislamiento & purificación
17.
Int J Mol Sci ; 18(5)2017 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-28475120

RESUMEN

Cadmium is a deleterious environmental pollutant that threats both animals and human health. Oxidative stress and elevated levels of reactive oxygen species (ROS) have recently been reported to be the main cause of cellular damage as a result of cadmium exposure. We investigate, here, the protective effect of strawberry crude extracts on cadmium-induced oxidative damage of testes in rats. Four groups (n = 8) of 32 adult male Wistar rats weighing 160-180 g were used. The control group received 0.9% saline solution all over the experimental period (5 days). Group 2 was intraperitoneally injected with 6.5 mg/kg CdCl2. Group 3 was provided only with an oral administration of strawberry methanolic extract (SME) at a dose of 250 mg/kg. Group 4 was treated with SME before cadmium injection with the same mentioned doses. It was shown that cadmium exposure results in a significant decrease in both relative testicular weight and serum testosterone level. Analyzing the oxidative damaging effect of cadmium on the testicular tissue revealed the induction of oxidative stress markers represented in the elevated level of lipid peroxidation (LPO), nitric oxide (NO), and a decrease in the reduced glutathione (GSH) content. Considering cadmium toxicity, the level of the antioxidant enzyme activities including catalase (CAT), superoxide dismutase (SOD2), glutathione peroxidase (GPx1), and glutathione reductase (GR) were markedly decreased. Moreover, gene expression analysis indicated significant upregulation of the pro-apoptotic proteins, bcl-2-associated-X-protein (BAX), and tumor necrosis factor-α (TNFA) in response to cadmium intoxication, while significant downregulation of the anti-apoptotic, B-cell lymphoma 2 (BCL2) gene was detected. Immunohistochemistry of the testicular tissue possessed positive immunostaining for the increased level of TNF-α, but decreased number of proliferating cell nuclear antigen (PCNA) stained cells. Administration of SME debilitated the deleterious effect of cadmium via reduction of both LPO and NO levels followed by a significant enhancement in the gene expression level of CAT, SOD2, GPX1, GR, nuclear factor-erythroid 2-related factor 2 (NFE2L2), heme oxygenase-1 (HMOX1), Bcl-2, and PCNA. In addition, the SME treated group revealed a significant increase in the level of testosterone and GSH accompanied by a marked decrease in the gene expression level of Bax and TNF-α. In terms of the summarized results, the SME of Fragaria ananassa has a protective effect against cadmium-induced oxidative damage of testes.


Asunto(s)
Antioxidantes/farmacología , Apoptosis , Cadmio/toxicidad , Fragaria/química , Peroxidación de Lípido , Extractos Vegetales/farmacología , Testículo/efectos de los fármacos , Animales , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Hemo Oxigenasa (Desciclizante)/metabolismo , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Óxido Nítrico/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Testículo/metabolismo
19.
BMC Complement Altern Med ; 16(1): 434, 2016 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-27821159

RESUMEN

BACKGROUND: Schistosomiasis is a prevalent parasitic disease found predominantly in tropical and sub-tropical areas of the developing world, with the second highest socioeconomic and public health burden despite strenuous control efforts. In the present study, we aimed to investigate the ameliorative effects of Ceratonia siliqua pod extract (CPE) on liver fibrosis and oxidative stress in mice infected with Schistosoma mansoni. METHODS: The schistosomal hepatopathologic mouse model was established by tail immersion with schistosomal cercaria. The extract was given daily for 10 days beginning 42 days post-infection. Liver samples were obtained from mice sacrificed 9 weeks after infection. Liver histopathological changes were observed with hematoxylin-eosin and Masson trichrome staining. RESULTS: Typical schistosomal hepatopathologic changes were induced in the untreated mice. However, the oral administration of CPE was effective in reducing worm number and the egg load in the liver. This treatment also decreased granuloma size and collagen deposition by inhibiting tissue inhibitor of metalloproteinases-2 (TIMP-2) expression. Schistosomal infection induced oxidative stress by increasing lipid peroxidation (LPO) and nitrite/nitrate (nitric oxide; NO) production along with concomitant decreases in glutathione (GSH) and various antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. However, treatment of mice with CPE at 300 or 600 mg/kg inhibited LPO and NO production, increased GSH content, and restored the activities of the antioxidant enzymes compared with untreated infected mice. Furthermore, treatment with CPE inhibited apoptosis, as indicated by the reduced Bax expression in hepatic tissue. CONCLUSION: These data indicated that extracts from Ceratonia siliqua pods may play an important role in combating schistosomal hepatopathology and may inhibit granuloma formation and liver fibrosis through down-regulation of TIMP-2 expression.


Asunto(s)
Fabaceae/química , Cirrosis Hepática/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Animales , Antioxidantes/metabolismo , Catalasa/genética , Catalasa/metabolismo , Glutatión/metabolismo , Humanos , Peroxidación de Lípido , Hígado/enzimología , Hígado/metabolismo , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/parasitología , Masculino , Ratones , Schistosoma mansoni/fisiología , Esquistosomiasis mansoni/genética , Esquistosomiasis mansoni/metabolismo , Esquistosomiasis mansoni/parasitología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/genética , Inhibidor Tisular de Metaloproteinasa-2/metabolismo
20.
PLoS One ; 11(8): e0161296, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27537199

RESUMEN

BACKGROUND: Leishmania is a unicellular protozoan parasite that produces several human diseases, ranging from localized self-healing cutaneous lesions to deadly visceral infections. OBJECTIVE: The effect of allicin on the growth of Leishmania major (L. major) promastigotes was evaluated under in vitro conditions. Moreover, the efficacy of a topical allicin cream was examined in BALB/c (Bagg albino, laboratory-bred strain of the House Mouse) mice with cutaneous leishmanial lesions compared to the currently used drug, sodiumstibogluconate (pentostam). METHODS: Cytotoxiciy and promastigote proliferation were measured. Different concentrations (50, 100, 150, and 200 µM) of liquid allicin were tested on L. major promastigotes twice: after 24 and 48 hours using an MTT colorimetric assay. In the in vivo condition, the efficacies of allicin cream and liquid allicin at two concentrations (0.15 µM/mouse and 0.30 µM/mouse) were evaluated. Serum factors of the control and treated groups were tested to evaluate the toxic effects of allicin on the liver and kidney. RESULTS: Allicin at a concentration of 50 µM inhibited the growth of Leishmania promastigotes. Topical application of allicin cream reduced lesion sizes in mice. No significant differences in biochemical analysis were observed between the control and treated groups. CONCLUSIONS: Allicin has antileishmanial effects under in vitro and in vivo conditions and may be used in clinical applications.


Asunto(s)
Antiprotozoarios/uso terapéutico , Leishmania major/efectos de los fármacos , Leishmaniasis Cutánea/tratamiento farmacológico , Ácidos Sulfínicos/uso terapéutico , Administración Cutánea , Animales , Antiprotozoarios/administración & dosificación , Femenino , Ratones , Ratones Endogámicos BALB C/parasitología , Crema para la Piel , Ácidos Sulfínicos/administración & dosificación
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