Antileishmanial Activity Of The Estrogen Receptor Modulator Raloxifene

dc.creatorReimao J.Q.
dc.creatorMiguel D.C.
dc.creatorTaniwaki N.N.
dc.creatorTrinconi C.T.
dc.creatorYokoyama-Yasunaka J.K.U.
dc.creatorUliana S.R.B.
dc.date2014
dc.date2015-06-25T17:55:20Z
dc.date2015-11-26T14:37:46Z
dc.date2015-06-25T17:55:20Z
dc.date2015-11-26T14:37:46Z
dc.date.accessioned2018-03-28T21:42:16Z
dc.date.available2018-03-28T21:42:16Z
dc.identifier
dc.identifierPlos Neglected Tropical Diseases. Public Library Of Science, v. 8, n. 5, p. - , 2014.
dc.identifier19352727
dc.identifier10.1371/journal.pntd.0002842
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-84901811639&partnerID=40&md5=7796ab18dad218bfe580865ca2ccb9b7
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/86803
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/86803
dc.identifier2-s2.0-84901811639
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1249261
dc.descriptionBackground:The treatment of leishmaniasis relies mostly on parenteral drugs with potentially serious adverse effects. Additionally, parasite resistance in the treatment of leishmaniasis has been demonstrated for the majority of drugs available, making the search for more effective and less toxic drugs and treatment regimens a priority for the control of leishmaniasis. The aims of this study were to evaluate the antileishmanial activity of raloxifene in vitro and in vivo and to investigate its mechanism of action against Leishmania amazonensis.Methodology/Principal Findings:Raloxifene was shown to possess antileishmanial activity in vitro against several species with EC50 values ranging from 30.2 to 38.0 μM against promastigotes and from 8.8 to 16.2 μM against intracellular amastigotes. Raloxifene's mechanism of action was investigated through transmission electron microscopy and labeling with propidium iodide, DiSBAC2(3), rhodamine 123 and monodansylcadaverine. Microscopic examinations showed that raloxifene treated parasites displayed autophagosomes and mitochondrial damage while the plasma membrane remained continuous. Nonetheless, plasma membrane potential was rapidly altered upon raloxifene treatment with initial hyperpolarization followed by depolarization. Loss of mitochondrial membrane potential was also verified. Treatment of L. amazonensis - infected BALB/c mice with raloxifene led to significant decrease in lesion size and parasite burden.Conclusions/Significance:The results of this work extend the investigation of selective estrogen receptor modulators as potential candidates for leishmaniasis treatment. The antileishmanial activity of raloxifene was demonstrated in vitro and in vivo. Raloxifene produces functional disorder on the plasma membrane of L. amazonensis promastigotes and leads to functional and morphological disruption of mitochondria, which culminate in cell death. © 2014 Reimão et al.
dc.description8
dc.description5
dc.description
dc.description
dc.descriptionAlvar, J., Velez, I.D., Bern, C., Herrero, M., Desjeux, P., Leishmaniasis Worldwide and Global Estimates of Its Incidence (2012) PLoS One, 7, pp. e35671
dc.descriptionCroft, S.L., Olliaro, P., Leishmaniasis chemotherapy-challenges and opportunities (2011) Clin Microbiol Infect, 17, pp. 1478-1483
dc.descriptionDorlo, T.P., Balasegaram, M., Beijnen, J.H., de Vries, P.J., Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis (2012) J Antimicrob Chemother, 67, pp. 2576-2597
dc.descriptionCroft, S.L., Sundar, S., Fairlamb, A.H., Drug resistance in leishmaniasis (2006) Clin Microbiol Rev, 19, pp. 111-126
dc.description(2010) Control of the leishmaniasis: Report of a meeting of the World Health Organization Expert Committee on the Control of Leishmaniases, , WHO. Geneva: WHO
dc.descriptionCroft, S.L., Seifert, K., Yardley, V., Current scenario of drug development for leishmaniasis (2006) Indian J Med Res, 123, pp. 399-410
dc.descriptionEkins, S., Williams, A.J., Krasowski, M.D., Freundlich, J.S., In silico repositioning of approved drugs for rare and neglected diseases (2011) Drug Discov Today, 16, pp. 298-310
dc.descriptionOsborne, C.K., Zhao, H., Fuqua, S.A., Selective estrogen receptor modulators: structure, function, and clinical use (2000) J Clin Oncol, 18, pp. 3172-3186
dc.descriptionCohen, I., Endometrial pathologies associated with postmenopausal tamoxifen treatment (2004) Gynecol Oncol, 94, pp. 256-266
dc.descriptionHeringa, M., Review on raloxifene: profile of a selective estrogen receptor modulator (2003) Int J Clin Pharmacol Ther, 41, pp. 331-345
dc.descriptionKo, S.S., Jordan, V.C., Treatment of osteoporosis and reduction in risk of invasive breast cancer in postmenopausal women with raloxifene (2011) Expert Opin Pharmacother, 12, pp. 657-674
dc.descriptionMiguel, D.C., Yokoyama-Yasunaka, J.K., Andreoli, W.K., Mortara, R.A., Uliana, S.R., Tamoxifen is effective against Leishmania and induces a rapid alkalinization of parasitophorous vacuoles harbouring Leishmania (Leishmania) amazonensis amastigotes (2007) J Antimicrob Chemother, 60, pp. 526-534
dc.descriptionMiguel, D.C., Zauli-Nascimento, R.C., Yokoyama-Yasunaka, J.K., Katz, S., Barbieri, C.L., Tamoxifen as a potential antileishmanial agent: efficacy in the treatment of Leishmania braziliensis and Leishmania chagasi infections (2009) J Antimicrob Chemother, 63, pp. 365-368
dc.descriptionEissa, M.M., Amer, E.I., El Sawy, S.M., Leishmania major: activity of tamoxifen against experimental cutaneous leishmaniasis (2011) Exp Parasitol, 128, pp. 382-390
dc.descriptionMiguel, D.C., Yokoyama-Yasunaka, J.K., Uliana, S.R., Tamoxifen is effective in the treatment of Leishmania amazonensis infections in mice (2008) PLoS Negl Trop Dis, 2, pp. e249
dc.descriptionLainson, R., Shaw, J.J., New World Leishmaniasis - The Neotropical Leishmania species (1998) Topley & Wilson's Microbiology and Microbial Infections, pp. 241-266. , In: Kreier JP WD, editor. London: F.E.G. Cox
dc.descriptionReimao, J.Q., Trinconi, C.T., Yokoyama-Yasunaka, J.K., Miguel, D.C., Kalil, S.P., Parasite burden in Leishmania (Leishmania) amazonensis-infected mice: Validation of luciferase as a quantitative tool (2013) J Microbiol Methods, 93, pp. 95-101
dc.descriptionArruda, D.C., D'Alexandri, F.L., Katzin, A.M., Uliana, S.R., Leishmania amazonensis: biosynthesis of polyprenols of 9 isoprene units by amastigotes (2008) Exp Parasitol, 118, pp. 624-628
dc.descriptionZamboni, D.S., Rabinovitch, M., Nitric oxide partially controls Coxiella burnetii phase II infection in mouse primary macrophages (2003) Infect Immun, 71, pp. 1225-1233
dc.descriptionZauli-Nascimento, R.C., Miguel, D.C., Yokoyama-Yasunaka, J.K., Pereira, L.I., Pelli de Oliveira, M.A., In vitro sensitivity of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis Brazilian isolates to meglumine antimoniate and amphotericin B (2010) Trop Med Int Health, 15, pp. 68-76
dc.descriptionMunafo, D.B., Colombo, M.I., A novel assay to study autophagy: Regulation of autophagosome vacuole size by amino acid deprivation (2001) J Cell Sci, 114, pp. 3619-3629
dc.descriptionFernandes, M.C., Da Silva, E.N., Pinto, A.V., de Castro, S.L., Menna-Barreto, R.F., A novel triazolic naphthofuranquinone induces autophagy in reservosomes and impairment of mitosis in Trypanosoma cruzi (2012) Parasitology, 139, pp. 26-36
dc.descriptionPinheiro, R.O., Nunes, M.P., Pinheiro, C.S., D'Avila, H., Bozza, P.T., Induction of autophagy correlates with increased parasite load of Leishmania amazonensis in BALB/c but not C57BL/6 macrophages (2009) Microbes Infect, 11, pp. 181-190
dc.descriptionLuque-Ortega, J.R., Rivas, L., Characterization of the leishmanicidal activity of antimicrobial peptides (2010) Methods Mol Biol, 618, pp. 393-420
dc.descriptionde Morais-Teixeira, E., Damasceno, Q.S., Galuppo, M.K., Romanha, A.J., Rabello, A., The in vitro leishmanicidal activity of hexadecylphosphocholine (miltefosine) against four medically relevant Leishmania species of Brazil (2011) Mem Inst Oswaldo Cruz, 106, pp. 475-478
dc.descriptionBiederbick, A., Kern, H.F., Elsasser, H.P., Monodansylcadaverine (MDC) is a specific in vivo marker for autophagic vacuoles (1995) Eur J Cell Biol, 66, pp. 3-14
dc.descriptionBesteiro, S., Williams, R.A., Morrison, L.S., Coombs, G.H., Mottram, J.C., Endosome sorting and autophagy are essential for differentiation and virulence of Leishmania major (2006) J Biol Chem, 281, pp. 11384-11396
dc.descriptionCustodio, J.B., Moreno, A.J., Wallace, K.B., Tamoxifen inhibits induction of the mitochondrial permeability transition by Ca2+ and inorganic phosphate (1998) Toxicol Appl Pharmacol, 152, pp. 10-17
dc.descriptionTaurin, S., Allen, K.M., Scandlyn, M.J., Rosengren, R.J., Raloxifene reduces triple-negative breast cancer tumor growth and decreases EGFR expression (2013) Int J Oncol, 43, pp. 785-792
dc.descriptionWang, Q., Lu, L., Gao, X., Wang, C., Wang, J., Effects of raloxifene on voltage-dependent T-type Ca2+ channels in mouse spermatogenic cells (2011) Pharmacology, 87, pp. 70-80
dc.descriptionBenaim, G., Garcia-Marchan, Y., Reyes, C., Uzcanga, G., Figarella, K., Identification of a sphingosine-sensitive Ca2+ channel in the plasma membrane of Leishmania mexicana (2013) Biochem Biophys Res Commun, 430, pp. 1091-1096
dc.descriptionPalit, P., Ali, N., Oral Therapy with Amlodipine and Lacidipine, 1,4-Dihydropyridine Derivatives Showing Activity against Experimental Visceral Leishmaniasis (2008) Antimicrob Agents Chemother, 52, pp. 374-377
dc.descriptionTempone, A.G., Taniwaki, N.N., Reimao, J.Q., Antileishmanial activity and ultrastructural alterations of Leishmania (L.) chagasi treated with the calcium channel blocker nimodipine (2009) Parasitol Res, 105, pp. 499-505
dc.descriptionReimao, J.Q., Scotti, M.T., Tempone, A.G., Anti-leishmanial and anti-trypanosomal activities of 1,4-dihydropyridines: In vitro evaluation and structure-activity relationship study Bioorg Med Chem, 18, pp. 8044-8053
dc.descriptionMorishima, S., Shibata, M.A., Ohmichi, M., Otsuki, Y., Raloxifene, a selective estrogen receptor modulator, induces mitochondria-mediated apoptosis in human endometrial carcinoma cells (2008) Med Mol Morphol, 41, pp. 132-138
dc.descriptionBursch, W., Ellinger, A., Kienzl, H., Torok, L., Pandey, S., Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy (1996) Carcinogenesis, 17, pp. 1595-1607
dc.descriptionde Medina, P., Silvente-Poirot, S., Poirot, M., Tamoxifen and AEBS ligands induced apoptosis and autophagy in breast cancer cells through the stimulation of sterol accumulation (2009) Autophagy, 5, pp. 1066-1067
dc.descriptionde Macedo-Silva, S.T., de Oliveira Silva, T.L., Urbina, J.A., de Souza, W., Rodrigues, J.C., Antiproliferative, Ultrastructural, and Physiological Effects of Amiodarone on Promastigote and Amastigote Forms of Leishmania amazonensis (2011) Mol Biol Int, 2011, p. 876021
dc.descriptionBera, A., Singh, S., Nagaraj, R., Vaidya, T., Induction of autophagic cell death in Leishmania donovani by antimicrobial peptides (2003) Mol Biochem Parasitol, 127, pp. 23-35
dc.descriptionLilly, E., Product monograph: Raloxifene hydrochloride (2008) Toronto
dc.descriptionReagan-Shaw, S., Nihal, M., Ahmad, N., Dose translation from animal to human studies revisited (2008) FASEB J, 22, pp. 659-661
dc.descriptionBonano, V.I., Yokoyama-Yasunaka, J.K.U., Miguel, D.C., Jones, S.A., Dodge, J.A., Discovery of Synthetic Leishmania Inhibitors by Screening of a 2-Arylbenzothiophene Library (2014) Chem Biol Drug Des, 83, pp. 289-296
dc.languageen
dc.publisherPublic Library of Science
dc.relationPLoS Neglected Tropical Diseases
dc.rightsaberto
dc.sourceScopus
dc.titleAntileishmanial Activity Of The Estrogen Receptor Modulator Raloxifene
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución