scholarly journals Cytotoxic Activities of Alkylphosphocholines against Clinical Isolates of Acanthamoeba spp

2002 ◽  
Vol 46 (3) ◽  
pp. 695-701 ◽  
Author(s):  
Julia Walochnik ◽  
Michael Duchêne ◽  
Karin Seifert ◽  
Andreas Obwaller ◽  
Thomas Hottkowitz ◽  
...  
Keyword(s):  
Chronic Conditions ◽  
Oral Treatment ◽  
Antineoplastic Agent ◽  
Cytotoxic Activities ◽  
Protozoan Parasites ◽  
Free Living ◽  
Human Visceral Leishmaniasis ◽  
Granulomatous Amoebic Encephalitis ◽  
Complete Cell

ABSTRACT Free-living amoebae of the genus Acanthamoeba are causing serious chronic conditions such as destructive keratitis in contact lens wearers or granulomatous amoebic encephalitis in individuals with compromised immune systems. Both are characterized by the lack of availability of sufficiently effective and uncomplicated, manageable treatments. Hexadecylphosphocholine (miltefosine) is licensed for use as a topical antineoplastic agent, but it is also active in vitro against several protozoan parasites, and it was applied very successfully for the treatment of human visceral leishmaniasis. The aim of our study was to evaluate the efficacy of hexadecylphosphocholine and other alkylphosphocholines (APCs) against Acanthamoeba spp. The in vitro activities of eight different APCs against three Acanthamoeba strains of various pathogenicities were determined. All substances showed at least amoebostatic effects, and some of them disrupted the amoebae, as shown by the release of cytoplasmic enzyme activity. Hexadecylphosphocholine exhibited the highest degree of cytotoxicity against trophozoites, resulting in complete cell death at a concentration as low as 40 μM, and also displayed significant cysticidal activity. Hexadecylphosphocholine may be a promising new candidate for the topical treatment of Acanthamoeba keratitis and, conceivably, even for the oral treatment of granulomatous amoebic encephalitis.

Laboratory diagnostics of Acanthamoeba spp. infections

2018 ◽  
Vol 54 (3) ◽  
pp. 173-178
Author(s):  
Aleksandra Bojanowska ◽  
Anna Bożym ◽  
Olga M. Koper-Lenkiewicz ◽  
Joanna Kamińska ◽  
Halina Kemona ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Laboratory Diagnosis ◽  
Etiologic Agent ◽  
Point Of View ◽  
The Body ◽  
Laboratory Diagnostics ◽  
Free Living ◽  
Granulomatous Amoebic Encephalitis ◽  
Clinical Point

Protozoa <i>Acanthamoeba</i> castellanii are single-celled, free-living, cosmopolitan amoebae that enter the body mainly through the mucous membrane of the mouth, nasal cavity, cornea, respiratory system, damaged skin and intestinal mucosa. In addition, they can be vectors for microorganisms such as bacteria, viruses, fungi and protozoa. In the life cycle A. castellanii may take the form of trophozoites and cyst tenacity to environmental conditions. This amoeba is an etiologic agent of dangerous human diseases: <i>Acanthamoeba</i> keratitis (AK), granulomatous amoebic encephalitis (GAE), pneumonia or changes in other organs, such as the liver, kidneys and skin. The aim of the article is to present current knowledge about laboratory diagnosis of <i>Acanthamoeba</i> spp. infection, which is based on the search for trophozoites and cysts in the material collected from the patient. In the case of suspected GAE, it is also advisable to study cerebrospinal fluid sediment and perform imaging tests such as computed tomography or magnetic resonance imaging. In the case of <i>Acanthamoeba</i> keratitis, an amoeba culture (obtained from a biopsy or corneal scrapings) is established in vitro, and then identified by light microscopy. The methods of molecular biology are also useful in detecting, identifying, and determining the potential pathogenic abilities of the amoebas. After the detection of <i>Acanthamoeba</i> spp., it is important to differentiate pathogenic isolates from non-pathogenic ones. From a clinical point of view, to diagnose <i>Acanthamoeba</i> spp. infection it is necessary only to identify the type of organism and to determine the pathogenicity of the isolate.

scholarly journals Inhibition of 3-Hydroxy-3-Methylglutaryl–Coenzyme A Reductase and Application of Statins as a Novel Effective Therapeutic Approach against Acanthamoeba Infections

2012 ◽  
Vol 57 (1) ◽  
pp. 375-381 ◽  
Author(s):  
Carmen María Martín-Navarro ◽  
Jacob Lorenzo-Morales ◽  
Rubén P. Machin ◽  
Atteneri López-Arencibia ◽  
José Manuel García-Castellano ◽  
...  
Keyword(s):  
Drug Target ◽  
Coenzyme A ◽  
Colorimetric Assay ◽  
Opportunistic Pathogen ◽  
Small Interfering Rnas ◽  
Free Living ◽  
Content Type ◽  
Granulomatous Amoebic Encephalitis ◽  
Coa Reductase

ABSTRACTAcanthamoebais an opportunistic pathogen in humans, whose infections most commonly manifest asAcanthamoebakeratitis or, more rarely, granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment ofAcanthamoeba, they are generally lengthy and/or have limited efficacy. Therefore, there is a requirement for the identification, validation, and development of novel therapeutic targets against these pathogens. Recently, RNA interference (RNAi) has been widely used for these validation purposes and has proven to be a powerful tool forAcanthamoebatherapeutics. Ergosterol is one of the major sterols in the membrane ofAcanthamoeba. 3-Hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase is an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, one of the precursors for the production of cholesterol in humans and ergosterol in plants, fungi, and protozoa. Statins are compounds which inhibit this enzyme and so are promising as chemotherapeutics. In order to validate whether this enzyme could be an interesting therapeutic target inAcanthamoeba, small interfering RNAs (siRNAs) against HMG-CoA were developed and used to evaluate the effects induced by the inhibition ofAcanthamoebaHMG-CoA. It was found that HMG-CoA is a potential drug target in these pathogenic free-living amoebae, and various statins were evaluatedin vitroagainst three clinical strains ofAcanthamoebaby using a colorimetric assay, showing important activities against the tested strains. We conclude that the targeting of HMG-CoA andAcanthamoebatreatment using statins is a novel powerful treatment option againstAcanthamoebaspecies in human disease.

Acanthamoeba spp. monoclonal antibody against a CPA2 transporter: a promising molecular tool for acanthamoebiasis diagnosis and encystment study

Parasitology ◽  
2020 ◽  
Vol 147 (14) ◽  
pp. 1678-1688
Author(s):  
Michele Martha Weber-Lima ◽  
Bianca Prado-Costa ◽  
Alessandra Becker-Finco ◽  
Adriana Oliveira Costa ◽  
Philippe Billilad ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Diagnostic Methods ◽  
Free Living ◽  
Immunoprecipitation Assay ◽  
Granulomatous Amoebic Encephalitis ◽  
Free Living Amoeba ◽  
Amoebic Keratitis ◽  
Low Sensitivity

AbstractFree-living amoeba of the genus Acanthamoeba are ubiquitous protozoa involved in opportunistic and non-opportunistic infection in humans, such as granulomatous amoebic encephalitis and amoebic keratitis. Both infections have challenging characteristics such as the formation of the resistant cysts in infected tissues, hampering the treatment and most usual diagnosis depending on time-consuming and/or low sensitivity techniques. The use of monoclonal antibodies presents itself as an opportunity for the development of more effective alternative diagnostic methods, as well as an important and useful tool in the search for new therapeutic targets. This study investigated the possibility of using a previously produced monoclonal antibody (mAb3), as a diagnostic tool for the detection of Acanthamoeba trophozoites by direct and indirect flow cytometry and immunofluorescence. Immunoprecipitation assay and mass spectrometry allowed the isolation of the antibody's target and suggested it is a transporter part of the CPA (cation: proton antiporter) superfamily. In vitro tests indicate an important role of this target in Acanthamoeba's encystment physiology. Our results support the importance of studying the role of CPA2 transporters in the context of acanthamoebiasis, as this may be a way to identify new therapeutic candidates.

Synthesis and Evaluation of Aromatic Surfactants as Potential Antibacterial and Cytotoxic Agents

2019 ◽  
Vol 16 (6) ◽  
pp. 478-484
Author(s):  
Kenia Barrantes ◽  
Mary Fuentes ◽  
Luz Chacón ◽  
Rosario Achí ◽  
Jorge Granados-Zuñiga ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Hela Cells ◽  
Cytotoxic Agents ◽  
Cytotoxic Activities ◽  
Hydroxybenzoic Acid ◽  
Derivatives Of

Two ether and one ester derivatives of the 4-nitro-3-hydroxybenzoic acid were synthesized and characterized. The in vitro antimicrobial and cytotoxic activities of the three novel compounds were also evaluated. The aromatic derivatives showed antibacterial activity against one of the four microorganisms tested and two compounds (C8 and NOBA) had a lower IC50 in HeLa cells.

Novel Hybrid Molecules of Quinazoline Chalcone Derivatives: Synthesis and Study of in vitro Cytotoxic Activities

2018 ◽  
Vol 15 (7) ◽  
pp. 757-765 ◽  
Author(s):  
Arunkumar Thiriveedhi ◽  
Ratnakaram Venkata Nadh ◽  
Navuluri Srinivasu ◽  
Kishore Kaushal
Keyword(s):  
Cytotoxic Activities ◽  
Chalcone Derivatives ◽  
Hybrid Molecules

In Vitro and In Vivo Neutralizing Activity of Uvaria chamae Leaves Fractions on the Venom of Naja nigricollis in Albino Rat and Bovine Blood

2020 ◽  
Vol 14 (4) ◽  
pp. 295-311
Author(s):  
Ada Gabriel ◽  
Mamman Mohammed ◽  
Mohammed G. Magaji ◽  
Yusuf P. Ofemile ◽  
Ameh P. Matthew ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Neglected Tropical Diseases ◽  
Lethal Dose ◽  
Positive Control ◽  
Haemolytic Activity ◽  
Cytotoxic Activities ◽  
Albino Rat ◽  
Aqueous Residue

Background: Snakebite envenomation is a global priority ranked top among other neglected tropical diseases. There is a folkloric claim that Uvaria chamae is beneficial for the management of snakebite and wounds in African ethnobotanical surveys. Besides, there are many registered patents asserting the health benefits of U. chamae. Objective: This study aimed to investigate U. chamae’s potentials and identify candidates for the development of tools for the treatment and management of N. nigricollis envenomation. Methods: Freshly collected U. chamae leaves were air-dried, powdered, and extracted in methanol. The median lethal dose of the extract was determined and further fractionated with n-hexane, n-butanol and ethyl acetate. Each fraction was tested for neutralizing effect against venom-induced haemolytic, fibrinolytic, hemorrhagic, and cytotoxic activities. Results: U. chamae fractions significantly (p<0.05) neutralized the haemolytic activity of N. nigricollis venom in n-butanol; 31.40%, n-hexane; 33%, aqueous residue; 39.60% and ethyl acetate; 40.70% at the concentration of 100mg/ml of each fraction against 10mg/ml of the snake venom when compared to the positive control. The fibrinolytic activity of N. nigricollis venom was significantly (p<0.05) neutralized in n-hexane at 73.88%, n-butanol; 72.22% and aqueous residue; 72.22% by the fractions of U. chamae. In addition, haemorrhagic activity of N. nigricollis venom was significantly (p<0.05) neutralized by U. chamae fractions at the concentrations of 100mg/ml, 200mg/ml and 400mg/ml except for n-butanol and aqueous residues at 400 mg/ml. Conclusion: U. chamae leaves fractions possess a high level of protection against N. nigricollis venoms-induced lethality and thus validate the pharmacological rationale for its usage in the management of N. nigricollis envenomation.

Flavonoids Extracted from Asteriscus graveolens Improve Glucose Metabo-lism and Lipid Profile in Diabetic Rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Fadwa El-ouady ◽  
Fatima Bachir ◽  
Mohamed Eddouks
Keyword(s):  
Glucose Tolerance ◽  
Lipid Profile ◽  
Histopathological Examination ◽  
Oral Treatment ◽  
Hdl Cholesterol ◽  
Diabetic Rats ◽  
Oral Glucose ◽  
Traditional Use ◽  
Soxhlet Apparatus

Aim: This study aimed to evaluate the antidiabetic and antihyperlipidemic effects of Asteriscus graveolens. Background: Asteriscus graveolens (Asteraceae) is a medicinal plant widely used by the Moroccan population to treat various diseases including diabetes. Objective: This work aimed to assess the capacity of flavonoids extracted from Asteriscus graveolens (FEE) to improve diabetes mellitus and dyslipidemia in normal and STZ-induced diabetic rats. Methods: Flavonoids were extracted from A. graveolens using the Soxhlet apparatus and using different organic solvents. Normal and streptozotocin-induced diabetic rats were treated orally by the extract of A. graveolens at a dose of 10 mg/kg. The oral treatment during 15 days was used to evaluate the effect of the flavonoids extracted from A. graveolens on blood glucose level and lipid profile in normal and diabetic rats. The oral glucose tolerance test as well as the analysis of histopathological examination of liver was performed. The antioxidant activity of FEE was also assessed by the method of trapping of free radical 2,2-diphenyl-1 picrylhydrazyl (DPPH), in order to estimate the mechanisms of action involved by FEE to improve hyperglycemia and lipid profile in normal and diabetic rats. Results: FEE reduced serum glucose concentrations in both normal and diabetic rats and exhibited in the last group lowering total cholesterol and triglycerides effects as well as improvement of the HDL-cholesterol serum level. In addition, a remarkable influence on glucose tolerance was also noticed after FEE treatment. Moreover, FEE was able to improve histopathological status of liver and possess a potential antioxidant effect in vitro. Conclusion: In conclusion, this study demonstrates the hypoglycemic and antihyperlipidemic effects of FEE in rats supporting then its traditional use for the management of diabetes.

scholarly journals In Vitro Cytotoxic Effects of Secondary Metabolites Present in Sarcopoterium Spinosum L.

2021 ◽  
Vol 11 (11) ◽  
pp. 5300
Author(s):  
Jozef Hudec ◽  
Jan Mojzis ◽  
Marta Habanova ◽  
Jorge A. Saraiva ◽  
Pavel Hradil ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Ethyl Acetate ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Benzalkonium Chloride ◽  
Ethanol Extract ◽  
Cytotoxic Activities ◽  
Sarcopoterium Spinosum ◽  
Mcf 7

Sarcopoterium spinosum (L.) is a medicinal plant traditionally used for the treatment of various diseases including cancer in the Near- and Middle East. The fractions and constituents of the ethanol extract of S. spinosum were screened for in vitro cytotoxic activities on Jurkat (acute T-lymphoblastic leukemia), HeLa (cervical adenocarcinoma), MCF-7 (mammary gland adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), and MDA-MB-231 (mammary gland adenocarcinoma) cell lines using the MTT (3-(dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The ethanol extract was subsequently re-extracted with ethyl acetate and in its sub-fraction obtained by column chromatography three compounds (stachydrine, benzalkonium chloride and rutine) were the first time identified by nuclear magnetic resonance (NMR) analyses. The most active subfraction showed cytotoxic activity against HeLa, MCF-7, and Caco-2 cell lines. The three compounds mentioned, as standards of high-performance liquid chromatography (HPLC) quality, were studied individually and in combination. Cytotoxic activity observed might be due to the presence of benzalkonium chloride and rutin. Benzalkonium chloride showed the strongest growth suppression effect against HeLa cells (IC50 8.10−7 M) and MCF-7 cells (IC50 5.10−6 M). The mixture of stachydrine and benzalkonium chloride allowed a synergistic cytotoxic effect against all tested cancer and normal cells to be obtained. Anti-cancer activity of the plant extract of S. spinosum remains under-investigated, so this research describes how the three major compounds identified in the ethyl acetate extract can exert a significant dose dependent in vitro cytotoxicity.

Sign in / Sign up

Export Citation Format

Share Document