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ACS Chem Neurosci ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31347828


Naegleria fowleri (N. fowleri) causes primary amoebic meningoencephalitis (PAM) which almost always results in death. N. fowleri is also known as "brain-eating amoeba" due to its literal infestation of the brain leading to an inflammatory response in the brain tissues. Currently, there is no single drug that is available to treat PAM, and most treatments are combinations of antifungal, anticancer, and anti-inflammatory drugs. Recently nanotechnology has gained attention in chemotherapeutic research converging on drug delivery, while oleic acid (OA) has shown positive effects on the human immune system and inflammatory processes. In continuation of our recent research in which we reported the effects of oleic acid conjugated with silver nanoparticles (OA-AgNPs) against free-living amoeba Acanthamoeba castellanii, in this report, we show their antiamoebic effects against N. fowleri. OA alone and its nanoconjugates were tested against the amoeba by using amoebicidal and host cell cytopathogenicity assays. Trypan blue exclusion assay was used to determine cell viability. The results revealed that OA-AgNPs exhibited significantly enhanced antiamoebic effects (P < 0.05) against N. fowleri as compared to OA alone. Evidently, lactate dehydrogenase release shows reduced N. fowleri-mediated host cell cytotoxicity. Based on our study, we anticipate that further studies on OA-AgNPs could potentially provide an alternative treatment of PAM.

Parasitol Res ; 118(7): 2295-2304, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31093751


Acanthamoeba castellanii belonging to the T4 genotype is an opportunistic pathogen which is associated with blinding eye keratitis and rare but fatal central nervous system infection. A. castellanii pose serious challenges in antimicrobial chemotherapy due to its ability to convert into resistant, hardy shell-protected cyst form that leads to infection recurrence. The fatty acid composition of A. castellanii trophozoites is known to be most abundant in oleic acid which chemically is an unsaturated cis-9-Octadecanoic acid and naturally found in animal and vegetable fats and oils. This study was designed to evaluate antiacanthamoebic effects of oleic acid against trophozoites, cysts as well as parasite-mediated host cell cytotoxicity. Moreover, oleic acid-conjugated silver nanoparticles (AgNPs) were also synthesized and tested against A. castellanii. Oleic acid-AgNPs were synthesized by chemical reduction method and characterized by ultraviolet-visible spectrophotometry, atomic force microscopy, dynamic light scattering analysis, and Fourier transform infrared spectroscopy. Viability, growth inhibition, encystation, and excystation assays were performed with 10 and 5 µM concentration of oleic acid alone and oleic acid-conjugated AgNPs. Bioassays revealed that oleic acid alone and oleic acid-conjugated AgNPs exhibited significant antiamoebic properties, whereas nanoparticle conjugation further enhanced the efficacy of oleic acid. Phenotype differentiation assays also showed significant inhibition of encystation and excystation at 5 µM. Furthermore, oleic acid and oleic acid-conjugated AgNPs also inhibited amoebae-mediated host cell cytotoxicity as determined by lactate dehydrogenase release. These findings for the first time suggest that oleic acid-conjugated AgNPs exhibit antiacanthamoebic activity that hold potential for therapeutic applications against A. castellanii.

Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba castellanii/efeitos dos fármacos , Amebicidas/farmacologia , Nanopartículas Metálicas/química , Ácido Oleico/farmacologia , Ceratite por Acanthamoeba/parasitologia , Amebicidas/química , Animais , Olho/parasitologia , Humanos , Microscopia de Força Atômica , Ácido Oleico/química , Prata/química , Espectrofotometria Ultravioleta , Trofozoítos/efeitos dos fármacos
Biomed Pharmacother ; 112: 108624, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784921


Rheumatoid arthritis (RA) is a chronic autoimmune disease of synovial inflammation and joint destruction. This study reports anti-arthritic potential of opuntioside-I opuntiol, and its gold and silver nanoparticles (NPs) against Complete Freund's Adjuvant (CFA)-induced arthritic rats. The mechanistic studies were performed targeting TLRs (TLR-2 and TLR-4) and cytokines (IL-1ß and TNF-α) expressions to validate their anti-inflammatory and immuno-modulatory response. The nano-formulations were successfully characterized employing Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) analysis. Opuntiol and opuntioside (OP and OPG: 10, 50 and 100 mg/kg) and opuntiol-coated silver and gold NPs (OP-AgNPs and OP-AuNPs: 0.5, 1 and 3 mg/kg) treatments in arthritic rat have shown minimal arthritic score exhibiting mild to moderate articular changes and tissue swelling in ankle joints. Radiographic examination reveals significant reduction in synovitis with improvement in joints degenarative changes in the presence of aforementioned treatments. Likewise, histology of rat ankle joints depicted comparatively lesser influx of inflammatory cells and diminished granulamatous inflammation. Moreover, treatment groups suppressed protein and mRNA expressions of TLRs (TLR-2 and TLR-4) and cytokines (IL-1ß and TNF-α) levels were also significantly declined in the presence of OPG, OP and its NPs comparing to arthritic control. This investigation concludes, the tested compounds and nano-formulations successfully restored the disease progression in CFA-induced arthritic rat owing to their immunomodulatory and anti-inflammatory potentials and can be considered for RA targeted therapy to address the utmost challenges of the disease.

Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Ácidos Cumáricos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Monossacarídeos/uso terapêutico , Receptor 2 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Antirreumáticos/administração & dosagem , Antirreumáticos/química , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Ácidos Cumáricos/administração & dosagem , Ácidos Cumáricos/química , Feminino , Adjuvante de Freund , Ouro/química , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Monossacarídeos/administração & dosagem , Monossacarídeos/química , Ratos Wistar , Prata/química