ESTATINAS COMO ALTERNATIVA TERAPÊUTICA PARA A TOXOPLASMOSE
Keywords:
toxoplasmose, Toxoplasma gondii, isoprenoides, estatinas.Abstract
A toxoplasmose, uma infecção causada pelo protozoário Toxoplasma gondii, assume caráter grave em indivíduos imunocomprometidos e em casos de infecção congênita. Dentre os vários processos celulares, a produção de precursores isoprenoides destaca-se como essencial para a sobrevivência deste protozoário. Sendo assim, fármacos, como as estatinas, que atuam na via do metabolismo de isoprenoides tornam-se importantes alternativas no tratamento da toxoplasmose, uma vez que a diminuição da biodisponibilidade de isoprenoides influencia negativamente a proliferação de T. gondii em células infectadas. Neste contexto, esta revisão relata estudos que investigaram a ação das estatinas como tratamento alternativo da toxoplasmose.
ABSTRACT
Toxoplasmosis, infection caused by Toxoplasma gondii, takes serious character in immunocompromised individuals and in cases of congenital infection. Among various cellular processes, the production of isoprenoid precursors is essential to the survival of this parasite. Thus, drugs such as statins, which act in isoprenoid metabolism, become important alternatives to treatment of toxoplasmosis, as the decrease in the bio-availability of isoprenoid has a negative effect on the proliferation of T. gondii into infected host cells. In this context, this review reports studies that investigated the action of statins as an alternative treatment for toxoplasmosis.
References
(1) SAADATNIA, G.; GOLKAR, M. A review on human toxoplasmosis. Scandinavian Journal of Infectious Diseases, Stockholm, v. 44, n. 11, p. 805-814, 2012.
(2) DUBEY, J. P.; LAGO, E. G.; GENNARI, S. M.; SU, C.; JONES, J. L. Toxoplasmosis in humans and animals in Brazil: high prevalence, high burden of disease, and epidemiology. Parasitolology, London, v. 139, n. 11, p.1375-1424, 2012.
(3) KAWAZOE, U.; MINEO, J. R. Toxoplasma gondii. In: Neves, D.P.; de MELO, A. L.; LINARDI, P. M.; VITOR, R. W. A. Parasitologia humana. 12a ed. São Paulo: Atheneu, Cap. 18, p. 163-172, 2011.
(4) MCAULEY, J. B. Congenital Toxoplasmosis. Journal of the Pediatric Infectious Diseases Society, Oxford, v. 3, p. S30-S35, 2014.
(5) MEIRA, C. S.; PEREIRA-CHIOCCOLA, V. L.; VIDAL, J. E.; DE MATTOS, C. C.; MOTOIE, G.; COSTA-SILVA, T. A.; GAVA, R.; FREDERICO, F. B.; DE MATTOS, L. C. Cerebral and ocular toxoplasmosis related with IFN-γ, TNF-α, and IL-10 levels. Frontiers in Microbiology, New York, v. 5, p. 492, 2014.
(6) DUBEY, J. P.; DENNIS, P. M.; VERMA, S. K.; CHOUDHARY, S.; FERREIRA, L. R.; OLIVEIRA, S.; KWOK, O. C. H.; BUTLER, E.; CARSTENSEN, M.; SU, C. Epidemiology of toxoplasmosis in white tailed deer (Odocoileus virginianus): occurrence, congenital transmission, correlates of infection, isolation, and genetic characterization of Toxoplasma gondii. Veterinary Parasitology, Amsterdam, v. 202, n. 3 - 4 p. 270-275, 2014.
(7) MONTOYA, J. G.; REMINGTON, J. S. Management of Toxoplasma gondii infection during pregnancy. Clinical Infectious Diseases, Chicago, v. 47, n. 4, p. 554-566, 2008.
(8) Centers for Disease Control and Prevention (CDC). Toxoplasmosis (Toxoplasma infection). Available in: http://www.cdc.gov/parasites/toxoplasmosis/biology.html, Access in: March 20, 2015.
(9) CARRUTHERS, V. B.; TOMLEY, F. M. Microneme proteins in apicomplexans. Subcellular Biochemistry, New York, v. 47, p. 33-45, 2008.
(10) DUBEY, J. P.; FRENKEL, J. K. Experimental Toxoplasma infection in mice with strains producing oocysts. Journal of Parasitology, Lawrence, v. 59, n. 3, p. 505-512, 1973.
(11) QIDWAI, T., KHAN, F. Antimalarial drugs and drug targets specific to fatty acid metabolic pathway of Plasmodium falciparum. Chemical Biology & Drug Design, Oxford, v. 80, n. 2, p. 155-172, 2012.
(12) BORST, P.; OVERDULVE, J.P.; WEIJERS, P. J.; FASE-FOWLER, F., VAN, DEN, BERG, M. DNA circles with cruciforms from Isospora (Toxoplasma) gondii. Biochimica et Biophysica Acta, Amsterdam, v. 781, n. 1-2, p. 100-111, 1984.
(13) WALLER, R. F.; MCFADDEN, G. I. The apicoplast: a review of the derived plastid of apicomplexan parasites. Current Issues in Molecular Biology, Wymondham, v. 7, n. 1, p. 57-79, 2005.
(14) SEEBER, F.; SOLDATI-FAVRE, D. Metabolic Pathways in the Apicoplast of Apicomplexa. International Review Of Cell and Molecular Biology, Knoxville, v. 281, p. 161-228, 2010.
(15) LIM, L.; LINKA, M.; MULLIN, K. A.; WEBER, A. P. M.; MCFADDEN, G. I. The carbon and energy sources of the non-photosynthetic plastid in the malaria parasite. Federation of European Biochemical Societies, Amsterdam, v. 584, n. 3, p. 549-554, 2010.
(16) DEROCHER, A. E.; KARNATAKI, A.; VANEY, P. PARSONS, M. Apicoplast targeting of a Toxoplasma gondii transmembrane protein requires a cytosolic tyrosine-based motif. Traffic, Malden, v.13, n. 5, p. 694-704, 2012.
(17) ANDERSON, A. C. Targeting DHFR in parasitic protozoa. Drug Discovery Today, Oxford, v. 10, n. 2, p. 121-128, 2005.
(18) PETERSEN, E. Toxoplasmosis.Seminars in fetal and neonatal medicine, Netherlands, v. 12, n. 3, p. 214-223, 2007.
(19) DEROUIN, F.; SANTILLANE-HAVAT, M. Anti-Toxoplasma Activities of Antiretroviral Drugs and Interactions with Pyrimethamine and Sulfadiazine in Vitro. Antimicrobial Agents and Chemotherapy, Washington, v. 44, n. 9, p. 2575-2577, 2000.
(20) ELSHEIKHA, H. M. Congenital toxoplasmosis: priorities for further health promotion action. Public Health, London, v.122, n. 4, p. 335-353, 2008.
(21) BARBOSA, M. A.; ANGELIN, L. G.; SAIKAWA, G. I. A.; OLIVEIRA, C. J. C.; SILVA, S. S.; VENDRUSCOLO, J. W.; MARINELLO, P. C.; FUJITA, C. T.; ROCHA, S. P. D.; WATANABE, M. A. E.; MITSUKA-BREGANÓ, R.; COSTA, I. N. Potenciais alternativas terapêuticas em estudo para toxoplasmose congenital: uma revisão bibliográfica. Revista de Patologia Tropical, Goiania, v. 44, n. 1, p. 1-11, 2015.
(22) CORTEZ, E.; STUMBO, A. C.; OLIVEIRA, M.; BARBOSA, H. S.; CARVALHO, L. Statins inhibit Toxoplasma gondii multiplication in macrophages in vitro. International journal of antimicrobial agents, Amsterdam, v. 33, n. 2, p. 185-186, 2009.
(23) LI, Z. H.; RAMAKRISHNAN, S.; STRIEPEN, B.; MORENO, S. N. Toxoplasma gondii relies on both host and parasite isoprenoids and can be rendered sensitive to atorvastatin. PLoS Pathogens, San Francisco, V. 9, n.10, p. 1-12, 2013.
(24) MASON, R. P. Molecular basis of differences among statins and a comparison with antioxidant vitamins. American Journal of Cardiology, New York, v. 98, n. 11, p. 34-41, 2006.
(25) GARCÍA-SABINA, A.; GULÍN-DÁVILA, J.; SEMPERE-SERRANO, P.; GONZÁLEZ-JUANATEY, C.; MARTÍNEZ-PACHECO, R. Consideraciones específicas en la prescripción e intercambio terapéutico de estatinas. Farmacia hospitalaria, Madrid, v. 36, n. 2, p. 97-108, 2012.
(26) GAZZERRO, P.; PROTO, M.C.; GANGEMI, G.; MALFITANO, A.M.; CIAGLIA, E.; PISANTI, S.; SANTORO, A.; LAEZZA, C.; BIFULCO, M. Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer. Pharmacological reviews, Baltimore, v. 64, n. 1:102-46, 2012.
(27) CHRISTIANS, U.; JACOBSEN, W.; FLOREN, L. C. Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in transplant patients: are the statins mechanistically similar? Pharmacol & Therapeutics, Oxford, v. 80, n. 1, p. 1–34, 1998.
(28) NISHIKAWA, Y.; IBRAHIM, H. M.; KAMEYAMA, K.; SHIGA, I.; HIASA, J.; XUAN, X. Host cholesterol synthesis contributes to growth of intracellular Toxoplasma gondii in macrophages. Journal of Veterinary Medical Science, Tokyo, v. 73, n. 5, p. 633-39, 2011.
(29) LIAO, J. K. Isoprenoids as mediators of the biological effects of statins. Journal of Clinical Investigation, New York, v. 110, n. 3, p. 285-288, 2002.
(30) COPPENS, I. Targeting, lipid biosynthesis and salvage in apicomplexan parasites for improved chemotherapies. Nature Review Microbiology, London, v.11, n. 12, p. 823-835, 2013.
(31) NAIR, S. C.; BROOKS, C. F.; GOODMAN, C. D.; STRURM, A.; MCFADDEN, G. I.; Sundriyal, S.; Anglin, J.L.; Song, Y.; Moreno, S.N.; Striepen, B. Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in Toxoplasma gondii. Journal of Experimental Medicine, New York, v. 208, n. 7, p. 1547–1559, 2011.
(32) SONDA, S.; HEHL, A. B. Lipid biology of Apicomplexa: perspectives for new drug targets, particularly for Toxoplasma gondii. Trends in Parasitology, Oxford v. 22, n. 1, p. 41-47, 2006.
(33) COPPENS, I. Exploitation of auxotrophies and metabolic defects in Toxoplasma as therapeutic approaches. International Journal for Parasitology, New York, v. 44, n. 2, p. 109-120, 2014.
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