Desenvolvimento do germe dentário e do palato em fetos de camundongos sob o efeito da Sinvastatina
Development of the tooth germ and palate in mouse embryos under effect of Sinvastatin
Florian, Fernanda; Faria, L.M.; Balducci, Eleny Zanella; Cirelli, Joni Augusto
Resumo
Introdução: As estatinas causaram uma revolução na prevenção e no tratamento do colesterol alto, porém é contraindicada no primeiro trimestre da gravidez, pois podem causar má formação no feto, no sistema nervoso central e nos membros. Objetivo: Verificar os efeitos da Sinvastatina na formação do palato e no desenvolvimento dos germes dentários dos primeiros molares superiores e inferiores. Material e método: Para o acasalamento, foram utilizados 14 camundongos fêmeas e quatro machos; o dia ‘zero’ da gestação foi identificado pelo plug vaginal após acasalamento. As fêmeas prenhes foram divididas em Grupos I e III - receberam 10 mg/kg solução salina em três semanas antes do acasalamento e a partir do acasalamento até o 14.º dia de prenhez, respectivamente. Grupos II e IV receberam 10 mg/kg de Sinvastatina, no perÃodo de três semanas antes do acasalamento e a partir do acasalamento até o 14.º dia de prenhez, respectivamente. Resultado: A análise histológica dos fetos dos Grupos I, II, III e IV mostrou o palato fusionado na linha mediana do processo palatino. Os germes dentários dos primeiros molares dos Grupos II e IV apresentaram um desenvolvimento atrasado quando comparados aos Grupos I e III, porém, todos estavam nas etapas de capuz e campânula. Conclusão: As análises histológica e estatÃstica mostraram que os fetos apresentaram palato fusionado na linha média de fusão do processo palatino e os germes dentários dos Grupos II e IV mostraram-se com formas indefinidas e contornos irregulares. Este estudo preliminar mostrou que a Sinvastatina pode ocasionar alterações morfológicas nos germes dentários.
Palavras-chave
Abstract
Introduction: The statins have been strongly used for the prevention and treatment of high cholesterol, but are contraindicated in the first trimester of pregnancy because they may cause fetal malformation, affecting the central nervous system and the limbs. Objective: To investigate the effects of simvastatin in palate formation and development of tooth germs of the first upper and lower molars. Material and method: Fourteen female and 4 male mice were used for breeding. The day "zero" of pregnancy was identified by vaginal plug after mating. The pregnant females were divided into four groups. Animals from Groups I and III received daily 10 mg / kg of saline three weeks before mating and from mating through day 14 of pregnancy, respectively. Animals from Groups II and IV received daily 10 mg/kg of simvastatin in the 3 weeks prior to mating and from mating through day 14 of pregnancy, respectively. Result: Histological evaluation of fetuses from Groups I to IV showed fused palate. The first molar tooth germs from Groups II and IV showed up with undefined forms and jagged edges suggesting a slower development compared to Groups I and III, although all the samples were at the bell or hood development stages. . Conclusion: This preliminary study showed that simvastatin does not affect palate fusion but can cause morphologic alterations in tooth germs of fetuses during gestation.
Keywords
References
1. Ten Cate AR. Histologia bucal. Rio de Janeiro: Guanabara-Koogan; 2001. PMCid:PMC2499591.
2. Katchburian E, Arana V. Histologia e embriologia oral. São Paulo: Panamericana; 2004. PMCid:PMC1571279.
3. Avery JK. Oral development and histology. New York: Thieme Medical Publishers; 1994.
4. Balducci-Roslindo E, Silvério KG, Jorge MA, Gonzaga HFS. Effect of isotretinoin on tooth germ and palate development in mouse embryons. Braz Dent J. 2001;12:115-9. PMid:11445913.
5. Balducci-Roslindo E, Silva VC, Peris AR, Silvério KG. Isotretinoin: action on mice tooth germs and palate. Braz J Oral Sci. 2002;1(3):121-5.
6. Freyssinges C, Ducrocq MB. Sinvastatin and pregnancy. Therapie. 1996;51(5):537-42. PMid:9138389.
7. Anbinder AL, Quirino MRS, Rocha RF. Statin and bone tissue: a literature review. Rev Odontol UNESP. 2006;35(4):239-46.
8. Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, et al. Stimulation of bone formation in vitro and in rodents by statins. Science. 1999;286:1946-9. PMid:10583956. http://dx.doi.org/10.1126/science.286.5446.1946
9. Chan KA, Andrade SE, Boles M, Buist DSM, Chase GA, Donahue JG, et al. Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women. Lancet. 2000;355(9222):2185-88. http://dx.doi.org/10.1016/S0140-6736(00)02400-4
10. LaCroix AZ, Cauley JA, Pettinger MMS, Hsia JMD, Bauer DC, McGowan J, et al. Statin use, clinical fracture, and bone density in postmenopausal women: results from the women's health initiative observational study. Ann Intern Med. 2003;139:97-104. PMid:12859159. http://dx.doi.org/10.7326/0003-4819-139-2-200307150-00009
11. Edison RJ, Muenke M. Gestational exposure to lovastatin followed by cardiac malformation misclassified as holoprosencephaly. N Engl J Med. 2005;352(26):275-9. PMid:15987932. http://dx.doi.org/10.1056/NEJM200506303522622
12. Edison RJ, Muenke M. Central nervous system and limb anomalies in case reports of first-trimester statin exposure. N Engl J Med. 2004;350:1579-82. PMid:15071140. http://dx.doi.org/10.1056/NEJM200404083501524
13. Edison RJ, Muenke M. Mechanistic and epidemiologic considerations in the evaluation of adverse birth outcomes following gestacional exposure to statins. Am J Med Genet A. 2004;131(3):287-98. PMid:15546153. http://dx.doi.org/10.1002/ajmg.a.30386
14. Kenis I, Tartakover-Matalon S, Cherepnin N, Drucker L, Fishman A, Pomeranz M, et al. Simvastatin has deleterious effects on human first trimester placental explants. Human Reproduction 2005;20:2866-72. PMid:15958395. http://dx.doi.org/10.1093/humrep/dei120
15. Manson JM, Freyssinges C, Ducrocq MB, Stephenson WP. Postmarkenting surveillance of lovastatin and simvastatin exposure during pregnancy. Reprod Toxicol. 1996;10(6):439-46. http://dx.doi.org/10.1016/S0890-6238(96)00130-X
16. Ofori B, Rey E, Bérard A. Risk of congenital anomalies in pregnant users of statin drugs. Braz J Clin Pharmacol. 2007;64(4):496-509. PMid:17506782 PMCid:PMC2048566. http://dx.doi.org/10.1111/j.1365-2125.2007.02905.x
17. Pollack PS, Shields KE, Burnett DM, Osborne MJ, Cunningham ML, Stepanavage ME. Pregnancy outcomes after maternal exposure to Simvastatin and Lovastatin. Birth Defects Research (Part A) 2005;73:888-96. PMid:16163683. http://dx.doi.org/10.1002/bdra.20181
18. Morse A. Formic acid sodium citrate decalcification and butyl alcohol dehidration of teeth and bone for sectioning in paraffin. J Dent Res. 1945;24(3/4):143-53. http://dx.doi.org/10.1177/00220345450240030501
19. Giannini SD, Forti N, Diament J, Issa JS. Aspectos terapêuticos das dislipidemias 2 - tratamento farmacológico - vastatinas: semelhanças e diferenças. Rev Soc Cardiol Estado de São Paulo. 1999;1:92-9.
20. Lefkowitz W, Bodecker CF, Mardfin DF. Odontogenesis of the rat. J Dent Res. 1953;32:749-72. PMid:13118019. http://dx.doi.org/10.1177/00220345530320060301
21. Conh SA. Development of the molar teeth in the mouse. Am J Anat. 1957;101:295-319. PMid:13508533. http://dx.doi.org/10.1002/aja.1001010205
22. Ayukawa Y, Okamura A, Koyano K. Sinvastatin promotes osteogenesis around titanium implants - a histological and histometrical study in rats. Clin Oral Impl Res. 2004;15:346-50. PMid:15142098. http://dx.doi.org/10.1046/j.1600-0501.2003.01015.x
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