Optimized combinations of statins and azoles against Acanthamoeba trophozoites and cysts in vitro
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摘要
Objective: To evaluate the combination of several statins(atorvastatin, fluvastatin and simvastatin) and azoles(voriconazole, posaconazole and itraconazole) against Acanthamoeba spp. Methods: The efficiency of the different drug combinations against the trophozoite stage of different Acanthamoeba strains were evaluated by Alamar Blue assay. Effect on the cyst stage was observed by inverted microscope. Cytotoxicity of combinations of azoles and statins was evaluated by measuring the release of lactate dehydrogenase from a murine macrophage cell line. Results: Combinations of any of the tested statins and voriconazole or posaconazole were more efficient in inhibiting Acanthamoeba compared to statins or azoles individually. The drug combinations at the combined inhibitory concentrations 50% showed lower toxicity compared to that of the compounds alone.Conclusions: The combinations of statins together with voriconazole and posaconazole are more efficient than these drugs alone, and these combinations have lower cytotoxicity in mammalian cell lines.
Objective: To evaluate the combination of several statins(atorvastatin, fluvastatin and simvastatin) and azoles(voriconazole, posaconazole and itraconazole) against Acanthamoeba spp. Methods: The efficiency of the different drug combinations against the trophozoite stage of different Acanthamoeba strains were evaluated by Alamar Blue assay. Effect on the cyst stage was observed by inverted microscope. Cytotoxicity of combinations of azoles and statins was evaluated by measuring the release of lactate dehydrogenase from a murine macrophage cell line. Results: Combinations of any of the tested statins and voriconazole or posaconazole were more efficient in inhibiting Acanthamoeba compared to statins or azoles individually. The drug combinations at the combined inhibitory concentrations 50% showed lower toxicity compared to that of the compounds alone.Conclusions: The combinations of statins together with voriconazole and posaconazole are more efficient than these drugs alone, and these combinations have lower cytotoxicity in mammalian cell lines.
Objective: To evaluate the combination of several statins(atorvastatin, fluvastatin and simvastatin) and azoles(voriconazole, posaconazole and itraconazole) against Acanthamoeba spp. Methods: The efficiency of the different drug combinations against the trophozoite stage of different Acanthamoeba strains were evaluated by Alamar Blue assay. Effect on the cyst stage was observed by inverted microscope. Cytotoxicity of combinations of azoles and statins was evaluated by measuring the release of lactate dehydrogenase from a murine macrophage cell line. Results: Combinations of any of the tested statins and voriconazole or posaconazole were more efficient in inhibiting Acanthamoeba compared to statins or azoles individually. The drug combinations at the combined inhibitory concentrations 50% showed lower toxicity compared to that of the compounds alone.Conclusions: The combinations of statins together with voriconazole and posaconazole are more efficient than these drugs alone, and these combinations have lower cytotoxicity in mammalian cell lines.
引文
[1]Lorenzo-Morales J,Martín-Navarro CM,López-Arencibi A,ArnalichMontiel F,Pi?ero JE,Valladares B.Acanthamoeba keratitis:An emerging disease gathering importance worldwide?Trends Parasitol 2013;29(4):181-187.
[2]Lorenzo-Morales J,Martín-Navarro CM,López-Arencibia A,SantanaMorales MA,Afonso-Lehmann RN,Maciver SK,et al.Therapeutic potential of a combination of two gene-specific small interfering RNAs against clinical strains of Acanthamoeba.Antimicrob Agents Chemother2010;54(12):5151-5155.
[3]Schuster FL,Visvesvara GS.Free-living amoebae as opportunistic and non-opportunistic pathogens of humans and animals.Int J Parasitol 2004;34(9):1001-1027
[4]Mafra CSP,Carrijo-Carvalho LC,Chudzinski-Tavassi AM,de Carvalho Taguchi FM,Foronda AS,de Souza Carvalho FR,et al.Antimicrobial action of biguanides on the viability of Acanthamoeba cysts and assessment of cell toxicity biguanides on Acanthamoeba cysts and cytotoxicity.Invest Ophthalmol Vis Sci 2013;54(9):6363-6372.287
[5]Martín-Navarro M,Lorenzo-Morales J,Machin RP,López-Arencibia A,García-Castellano JM,de Fuentes I,et al.Inhibition of 3-Hydroxy-3-Methylglutaryl-coenzyme a reductase and application of statins as a novel effective therapeutic approach against Acanthamoeba infections.Antimicrob Agents Chemother 2013;57(1):375-381.
[6]Martín-Navarro CM,López-Arencibia A,Arnalich-Montiel F,Valladares B,Pi?ero JE,Lorenzo-Morales J.Evaluation of the in vitro activity of commercially available moxifloxacin and voriconazole eye-drops against clinical strains of Acanthamoeba.Graefes Arch Clin Exp Ophthalmol 2013;251(9):2111-2117.
[7]Collins R,Reith C,Emberson J,Armitage J,Baigent C,Blackwell L,et al.Interpretation of the evidence for the efficacy and safety of statin therapy.Lancet 2016;388(10059):2532-2561.
[8]Martín-Navarro CM,López-Arencibia A,Sifaoui I,Reyes-Batlle M,Valladares B,Martínez-Carretero E,et al.Statins and voriconazole induce programmed cell death in Acanthamoeba castellanii.Antimicrob Agents Chemother 2015;59(5):2817-2824.
[9]Smith FR,Korn ED.7-Dehydrostigmasterol and ergosterol:The major sterols of an amoeba.J Lipid Res 1968;9(4):405-408.
[10]Iovieno A,Miller D,Ledee DR,Alfonso EC.Cysticidal activity of antifungals against different genotypes of Acanthamoeba.Antimicrob Agents Chemother 2014;58(9):5626-5628.
[11]Mehdi H,Garg HS,Garg NK,Bhakuni DS.Sterols of Acanthamoeba culbertsoni strain A-1.Steroids 1988;51(5):551-558.
[12]Arnalich-Montiel F,Martín-Navarro CM,AlióJL,López-Vélez R,Martínez-Carretero E,Valladares B,et al.Successful monitoring and treatment of intraocular dissemination of Acanthamoeba.Arch Ophthalmol2012;130(11):1474-1475.
[13]Schiller DS,Fung HB.Posaconazole:An extended-spectrum triazole antifungal agent.Clin Ther 2007;29(9):1862-1886.
[14]Oliva S,Jantz M,Tiernan R,Cook DL,Judson MA.Successful treatment of widely disseminated acanthamoebiasis.South Med J 1999;92:55-57.
[15]McBride J,Ingram PR,Henriquez FL,Roberts CW.Development of colorimetric microtiter plate assay for assessment of antimicrobials against Acanthamoeba.J Clin Microbiol 2005;43(2):629-634.
[16]Martín-Navarro CM,Lorenzo-Morales J,Cabrera-Serra MG,Rancel F,Coronado-Alvarez NM,Pinero JE,et al.The potential pathogenicity of chlorhexidine-sensitive Acanthamoeba strains isolated from contact lens cases from asymptomatic individuals in Tenerife,Canary Islands,Spain.J Med Microbiol 2008;57(11):1399-1404.
[17]Lorenzo-Morales J,Kliescikova J,Martinez-Carretero E,De Pablos LM,Profotova B,Nohynkova E,et al.Glycogen phosphorylase in Acanthamoeba spp.:Determining the role of the enzyme during the encystment process using RNA interference.Eukaryotic cell 2008;7(3):509-517.
[18]Martín-Navarro CM,López-Arencibia A,Sifaoui I,Reyes-Batlle M,Fouque E,Osuna A,et al.Amoebicidal activity of caffeine and maslinic acid by the induction of programmed cell death in Acanthamoeba.Antimicrob Agents Chemother 2017;61(6):e02660-e02616.
[19]Kulsoom H,Baig AM,Siddiqui R,Khan NA.Combined drug therapy in the management of granulomatous amoebic encephalitis due to Acanthamoeba spp.,and Balamuthia mandrillaris.Exp Parasitol 2014;145:S115-S120.
[20]Montalvetti A,Javier PA,Hurtado R,Ruiz-Pérez LM,GonzálezPacanowska D.Characterization and regulation of Leishmania major3-hydroxy-3-methylglutaryl-CoA reductase.Biochem J 2000;349(1):27-34.
[21]Ishibashi Y,Matsumoto Y,Kabata T,Watanabe R,Hommura S,Yasuraoka K,et al.Oral itraconazole and topical miconazole with debridement for Acanthamoeba keratitis.Am J Ophthalmol 1990;109(2):121-126.
[2]Lorenzo-Morales J,Martín-Navarro CM,López-Arencibia A,SantanaMorales MA,Afonso-Lehmann RN,Maciver SK,et al.Therapeutic potential of a combination of two gene-specific small interfering RNAs against clinical strains of Acanthamoeba.Antimicrob Agents Chemother2010;54(12):5151-5155.
[3]Schuster FL,Visvesvara GS.Free-living amoebae as opportunistic and non-opportunistic pathogens of humans and animals.Int J Parasitol 2004;34(9):1001-1027
[4]Mafra CSP,Carrijo-Carvalho LC,Chudzinski-Tavassi AM,de Carvalho Taguchi FM,Foronda AS,de Souza Carvalho FR,et al.Antimicrobial action of biguanides on the viability of Acanthamoeba cysts and assessment of cell toxicity biguanides on Acanthamoeba cysts and cytotoxicity.Invest Ophthalmol Vis Sci 2013;54(9):6363-6372.287
[5]Martín-Navarro M,Lorenzo-Morales J,Machin RP,López-Arencibia A,García-Castellano JM,de Fuentes I,et al.Inhibition of 3-Hydroxy-3-Methylglutaryl-coenzyme a reductase and application of statins as a novel effective therapeutic approach against Acanthamoeba infections.Antimicrob Agents Chemother 2013;57(1):375-381.
[6]Martín-Navarro CM,López-Arencibia A,Arnalich-Montiel F,Valladares B,Pi?ero JE,Lorenzo-Morales J.Evaluation of the in vitro activity of commercially available moxifloxacin and voriconazole eye-drops against clinical strains of Acanthamoeba.Graefes Arch Clin Exp Ophthalmol 2013;251(9):2111-2117.
[7]Collins R,Reith C,Emberson J,Armitage J,Baigent C,Blackwell L,et al.Interpretation of the evidence for the efficacy and safety of statin therapy.Lancet 2016;388(10059):2532-2561.
[8]Martín-Navarro CM,López-Arencibia A,Sifaoui I,Reyes-Batlle M,Valladares B,Martínez-Carretero E,et al.Statins and voriconazole induce programmed cell death in Acanthamoeba castellanii.Antimicrob Agents Chemother 2015;59(5):2817-2824.
[9]Smith FR,Korn ED.7-Dehydrostigmasterol and ergosterol:The major sterols of an amoeba.J Lipid Res 1968;9(4):405-408.
[10]Iovieno A,Miller D,Ledee DR,Alfonso EC.Cysticidal activity of antifungals against different genotypes of Acanthamoeba.Antimicrob Agents Chemother 2014;58(9):5626-5628.
[11]Mehdi H,Garg HS,Garg NK,Bhakuni DS.Sterols of Acanthamoeba culbertsoni strain A-1.Steroids 1988;51(5):551-558.
[12]Arnalich-Montiel F,Martín-Navarro CM,AlióJL,López-Vélez R,Martínez-Carretero E,Valladares B,et al.Successful monitoring and treatment of intraocular dissemination of Acanthamoeba.Arch Ophthalmol2012;130(11):1474-1475.
[13]Schiller DS,Fung HB.Posaconazole:An extended-spectrum triazole antifungal agent.Clin Ther 2007;29(9):1862-1886.
[14]Oliva S,Jantz M,Tiernan R,Cook DL,Judson MA.Successful treatment of widely disseminated acanthamoebiasis.South Med J 1999;92:55-57.
[15]McBride J,Ingram PR,Henriquez FL,Roberts CW.Development of colorimetric microtiter plate assay for assessment of antimicrobials against Acanthamoeba.J Clin Microbiol 2005;43(2):629-634.
[16]Martín-Navarro CM,Lorenzo-Morales J,Cabrera-Serra MG,Rancel F,Coronado-Alvarez NM,Pinero JE,et al.The potential pathogenicity of chlorhexidine-sensitive Acanthamoeba strains isolated from contact lens cases from asymptomatic individuals in Tenerife,Canary Islands,Spain.J Med Microbiol 2008;57(11):1399-1404.
[17]Lorenzo-Morales J,Kliescikova J,Martinez-Carretero E,De Pablos LM,Profotova B,Nohynkova E,et al.Glycogen phosphorylase in Acanthamoeba spp.:Determining the role of the enzyme during the encystment process using RNA interference.Eukaryotic cell 2008;7(3):509-517.
[18]Martín-Navarro CM,López-Arencibia A,Sifaoui I,Reyes-Batlle M,Fouque E,Osuna A,et al.Amoebicidal activity of caffeine and maslinic acid by the induction of programmed cell death in Acanthamoeba.Antimicrob Agents Chemother 2017;61(6):e02660-e02616.
[19]Kulsoom H,Baig AM,Siddiqui R,Khan NA.Combined drug therapy in the management of granulomatous amoebic encephalitis due to Acanthamoeba spp.,and Balamuthia mandrillaris.Exp Parasitol 2014;145:S115-S120.
[20]Montalvetti A,Javier PA,Hurtado R,Ruiz-Pérez LM,GonzálezPacanowska D.Characterization and regulation of Leishmania major3-hydroxy-3-methylglutaryl-CoA reductase.Biochem J 2000;349(1):27-34.
[21]Ishibashi Y,Matsumoto Y,Kabata T,Watanabe R,Hommura S,Yasuraoka K,et al.Oral itraconazole and topical miconazole with debridement for Acanthamoeba keratitis.Am J Ophthalmol 1990;109(2):121-126.