Gestational exposure to Byrsonima verbascifolia: Teratogenicity, mutagenicity and immunomodulation evaluation in female Swiss mice Caroline Amélia Gonçalves a,b , João Máximo Siqueira c,d,e , Carlos Alexandre Carollo b,f , Mariana de Oliveira Mauro a , Natan de Davi f , Andréa Luiza Cunha-Laura f , Antônio Carlos Duenhas Monreal f , Ana Hortencia Castro d,e , Lucas Fernandes d,e , Rafael Russo Chagas d , Sarah Alves Auharek c,f , Rodrigo Juliano Oliveira a,b,c,n a Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica (CeTroGen), Núcleo de Hospital Universitário (NHU), Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil b Programa de Pós-graduação em Farmácia, Centro de Ciências Biológicas e da Saúde (CCBS), Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil c Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Faculdade de Medicina “Dr. Hélio Mandetta” (FAMED), Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil d Campus Centro-Oeste Dona Lindu, Universidade Federal de São João Del-Rei (UFSJ), Divinópolis, Minas Gerais, Brazil e Programa de Pós-Graduação em Ciências da Saúde, Campus CCO – Dona Lindu, Universidade Federal de São João Del-Rei (UFSJ), Divinópolis, Minas Gerais, Brazil f Centro de Ciências Biológicas e da Saúde (CCBS), Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil article info Article history: Received 12 July 2013 Received in revised form 1 September 2013 Accepted 6 September 2013 Available online 16 October 2013 Keywords: Byrsonima verbascifolia Medicinal plant Toxicity Teratogenicity Micronucleus abstract Ethnopharmacological relevance: Byrsonima verbascifolia is used in folk medicine to treat diarrhea, intestinal infections, chronic wounds, Chagas disease, inflammation and as a diuretic. However there is no investigation regarding the Byrsonima verbascifolia hydrometanolic extract (BVHME) used during gestation. Materials and methods: The pregnant females were randomly divided into 5 groups. Control group received saline plus DMSO (1%) in a volume of 0.1 mL/10 g (b.w.), via gavage, for at least 15 days prior to mating and throughout the gestational period. The Pre-treatment group received the BVHME, via gavage, at a dose of 50 mg/kg (b.w.) for at least 15 days prior to mating and up to the appearance of the vaginal plug. The Organogenesis group received the BVHME at a dose of 50 mg/kg (b.w.), via gavage, on the 5–15th gestational day. The Gestational group received the BVHME at a dose of 50 mg/kg (b.w.), via gavage, throughout the gestational period (from the 1st to the 18th day of pregnancy). The Pre þGestational group received the BVHME at a dose of 50 mg/kg (b.w.), via gavage, for at least 15 days prior to mating and up to throughout the gestational period. The clinical signals of maternal and fetuses toxicity were evaluated, as the mutagenicity and immunomodulation tests were performed. Results and conclusions: The present investigation shows, for the first time, that the use of Byrsonima verbascifolia extract in pregnant Swiss mice, did not alter the female reproductive function, mutagenicity or immunostimulation as well as not interfere with embryofetal development at least in our experimental conditions. & 2013 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Byrsonima verbascifolia, (Malpighiaceae), popularly known as “murici”, “murici-cascudo” (Rodrigues and Carvalho, 2001) “mirici” and “douradinha-falsa” can be found throughout tropical America (Mamede, 1982) with a predominance in the Brazilian cerrado (Batista et al., 2005). Byrsonima verbascifolia is used in folk medicine to treat diarrhea, intestinal infections, chronic wounds, Chagas disease, inflammation of the oral cavity, throat and the female genital tract (Panizza, 1998). Some reports showed the popular use of Byrsonima verbascifolia as a diuretic (Rodrigues and Carvalho, 2001), laxative, astringent, anti-pyretic and in the treatment of cough and bronchitis (Almeida et al., 1998). It is also has antiviral and antimicrobial effects as well as the absence of cytotoxicity (Khan et al., 2005). Phytochemical analysis of the Byrsonima verbascifolia leaves indicate the presence of quercetin derivatives, α-amirin, oleanoic acid and ursolic acid (Guilhon-Simplicio and Pereira, 2011) Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jep Journal of Ethnopharmacology 0378-8741/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jep.2013.09.012 n Corresponding author at: Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica (CeTroGen), Núcleo de Hospital Universitário (NHU), Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil. Tel./fax: þ55 67 3345 7671. E-mail addresses: rodrigo.oliveira@ufms.br, rjo.ead.ufms@gmail.com (R. Juliano Oliveira). Journal of Ethnopharmacology 150 (2013) 843–850