Antifungal activity of some cyclooxygenase inhibitors on Candida albicans: PGE2-dependent mechanism

Quadros, Andreza Urba de; Bini, Daniel; Pereira, Priscilla Aparecida Tártari; Moroni, Estela Glória; Monteiro, Marta Chagas

doi:10.1007/s12223-011-0049-6

Cited by 30 publications

(23 citation statements)

References 19 publications

(29 reference statements)

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“…This result could be explained in part by differences between our strains and those used in other studies. Previous reports have assayed biofilms with strains isolated from skin lesions [18], DS [16], sputum, the ear, and blood [20], as well as standard ATCC strains [37]. Given that the phenotype of C .…”

Section: Discussionmentioning

confidence: 99%

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients

et al. 2017

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Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro. Disk diffusion assays showed that while NO-ASA had no antifungal effect, the drug potentiated fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20–30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was evaluated using light microscopy after inducing hyphae formation. For all clinical strains assayed, 125 μM NO-ASA significantly decreased the number of filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical event for biofilm formation, was evaluated in 96-well polystyrene plates using crystal violet assay; 125 μM NO-ASA significantly inhibited adhesion. Biofilms were observed with scanning electron microscopy (SEM) and quantified using XTT reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 μM to 700 μM), consistent with SEM findings of altered biofilm microarchitecture. PGE2 and carboxy-PTIO (an NO scavenger) both blocked the antibiofilm effects of NO-ASA, suggesting that the efficacy of NO-ASA may be associated with both inhibition of PGE2 synthesis and release of NO. NO-ASA is a promising novel antibiofilm agent for treating fluconazole-resistant strains of C. albicans.

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Section: Discussionmentioning

confidence: 99%

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients

et al. 2017

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“…It can inhibit fungal prostaglandin synthesis and therefore reduce biofilm development in C. albicans (Alem and Douglas, 2004, 2005; Ghalehnoo et al, 2010; Bink et al, 2012; Rusu et al, 2014). They inhibit the growth of C. albicans in a dose-dependent manner (de Quadros et al, 2011). Among them, indomethacin, a potent COX inhibitor, is most effective against C. albicans (MFC 0.11 mmol/L), followed by aspirin (MFC 0.22 mmol/L) and ibuprofen (MFC 0.44 mmol/L), while sodium salicylate isconsiderably less potent (MFC 22 mmol/L) than the other tested NSAIDs.…”

Section: Cyclooxygenasementioning

confidence: 99%

“…In a murine model of systemic infection, the combination of ibuprofen, and fluconazole can potentiate the antifungal activity of fluconazole by decreasing the MIC of fluconazole from 64 to 2 μg/ml and reduce the fungal burden and morbidity in fluconazole resistant strains (Pina-Vaz et al, 2000; Arai et al, 2005; Costa-de-Oliveira et al, 2015). As a potential Cdrp blocker, ibuprofen can directly damage C. albicans cell membranes, but the molecular mechanisms of ibuprofen against C. albicans are still being uncovered (Ricardo et al, 2009; de Quadros et al, 2011). Anidulafungin (ANF) is an antifungal drug that can inhibit the formation of both planktonic and biofilms cells in C. albicans .…”

Section: Cyclooxygenasementioning

confidence: 99%

Potential Antifungal Targets against a Candida Biofilm Based on an Enzyme in the Arachidonic Acid Cascade—A Review

Liu

Wang

et al. 2016

Front. Microbiol.

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Candida is an important opportunistic fungal pathogen, especially in biofilm associated infections. The formation of a Candida biofilm can decrease Candida sensitivity to antifungal drugs and cause drug resistance. Although many effective antifungal drugs are available, their applications are limited due to their high toxicity and cost. Seeking new antifungal agents that are effective against biofilm-associated infection is an urgent need. Many research efforts are underway, and some progress has been made in this field. It has been shown that the arachidonic acid cascade plays an important role in fungal morphogenesis and pathogenicity. Notably, prostaglandin E2 (PGE2) can promote the formation of a Candida biofilm. Recently, the inhibition of PGE2 has received much attention. Studies have shown that cyclooxygenase (COX) inhibitors, such as aspirin, ibuprofen, and indomethacin, combined with fluconazole can significantly reduce Candida adhesion and biofilm development and increase fluconazole susceptibility; the MIC of fluconazole can be decrease from 64 to 2 μg/ml when used in combination with ibuprofen. In addition, in vivo studies have also confirmed the antifungal activities of these inhibitors. In this article, we mainly review the relationship between PGE2 and Candida biofilm, summarize the antifungal activities of COX inhibitors and analyze the possible antifungal activity of microsomal prostaglandin E synthase-1 (MPGES-1) inhibitors; additionally, other factors that influence PGE2 production are also discussed. Hopefully this review can disclose potential antifungal targets based on the arachidonic acid cascade and provide a prevailing strategy to alleviate Candida albicans biofilm formation.

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“…COX-dependent pathways may be responsible for the prostaglandin (PGE2) synthesis in C. albicans , and prostaglandin induces pathogenicity in C. albicans [30,31]. COX-II inhibitors inhibit morphogenesis and biofilm formation in C. albicans [32].…”

Section: Resultsmentioning

confidence: 99%

Anti-Candida properties of asaronaldehyde of Acorus gramineus rhizome and three structural isomers

et al. 2013

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BackgroundAsaronaldehyde (2, 4, 5-trimethoxybeznaldehyde) is an active component of Acorus gramineus rhizome. This study aims to evaluate the anti-Candida efficacy of asaronaldehyde and its three structural isomers, namely, 2, 3, 4-trimethoxybenzaldehyde, 3, 4, 5-trimethoxybenzaldehyde, and 2, 4, 6- trimethoxybenzaldehyde.MethodsSusceptibility testing of test compounds was carried out using standard methodology (M27-A2) as per clinical and laboratory standards institute guidelines. Minimum fungicidal concentration (MFC) was determined as the lowest concentration of drug killing 99.9% of Candida cells. The effect on sterol profile was evaluated using the ergosterol quantitation method. Effects on morphogenesis, adhesion and biofilm formation in C. albicans were studied using germ-tube, adherence and biofilm formation assays respectively. Cytotoxicity of test compounds to human RBCs was determined by hemolysis assay.Results2, 4, 6-Trimethoxybenzaldehyde exhibited significant anti-Candida activity (P = 0.0412). Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were established as 0.25 and 0.5 mg/mL, respectively. All of the test compounds showed significant inhibition of hyphal form transition in yeast at MIC/2 and MIC/4 values. 3, 4, 5-Trimethoxybenzaldehyde and 2, 4, 6-trimethoxybenzaldehyde inhibited adhesion and biofilms. A hemolytic assay of these compounds revealed that they were non-toxic at MIC values. Asaronaldehyde reduced sterol content.ConclusionAsaronaldehyde and 2, 4, 6-trimethoxybenzaldehyde showed anti-Candida efficacy.

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Antifungal activity of some cyclooxygenase inhibitors on Candida albicans: PGE2-dependent mechanism

Cited by 30 publications

References 19 publications

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients

Potential Antifungal Targets against a Candida Biofilm Based on an Enzyme in the Arachidonic Acid Cascade—A Review

Anti-Candida properties of asaronaldehyde of Acorus gramineus rhizome and three structural isomers

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