The Ethanolic Extract of Piper glabratum Kunth Is Teratogenic and Interferes with the Ossification Process of Swiss Mice Fetuses

Author:

Nunes Rogério Carlos Sanfelice12,Neves Silvia Cordeiro das12ORCID,Salustriano Fabricia Rodrigues1,Vilela Marcelo Luiz Brandão3,Nascimento Valter Aragão do2ORCID,Arunachalam Karuppusamy12ORCID,Gomes Roberto da Silva4ORCID,Kassuya Candida Aparecida Leite5ORCID,Mota Jonas da Silva6,Oliveira Rodrigo Juliano12ORCID

Affiliation:

1. Centro de Estudos em Células-Tronco, Terapia Celular e Genética Toxicológica (CeTroGen), Faculdade de Medicina (FAMED), Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Mato Grosso do Sul, Brazil

2. Programa de Pós-graduação em Saúde e Desenvolvimento da Região Centro-Oeste, Faculdade de Medicina (FAMED), Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Mato Grosso do Sul, Brazil

3. Faculdade de Medicina Dr. Hélio Mandetta (FAMED), Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande 79070-900, Mato Grosso do Sul, Brazil

4. Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA

5. Faculdade de Ciências da Saúde, Universidade Federal da Grande Dourados (UFGD), Dourados 79825-070, Mato Grosso do Sul, Brazil

6. Departamento de Química, Universidade Estadual de Mato Grosso do Sul (UEMS), Dourados 79804-970, Mato Grosso do Sul, Brazil

Abstract

Piper glabratum Kunth is a plant traditionally used to treat pain and inflammation in the Mato Grosso do Sul, Brazil. Even pregnant women consume this plant. Toxicology studies of the ethanolic extract from the leaves of P. glabratum (EEPg) could establish the safety of popular use of P. glabratrum. Thus, the effects of the ethanolic extract of leaves of P. glabratum (EEPg) on the reproductive performance and embryofetal development of Swiss mice were evaluated. Pregnant female mice were treated with 100, 1000 and 2000 mg/kg throughout the gestational period by gavage (p.o). The control group received the EEPg vehicle (Tween 80–1%) in the proportion of 0.1 mL/10 g (p.o.). The results demonstrated that EEPg has low maternal toxic potential and does not alter the reproductive performance of females. However, it altered embryofetal development and caused fetal weight reduction (increasing the frequency of small-for-gestational-age fetuses) at the two highest doses. In addition, it interfered with placental weight, placental index and placental efficiency. The frequency of visceral malformations increased by 2.8 times for the lowest dose of EEPg, and skeletal malformations increased by 2.48, 1.89 and 2.11 times for doses of 100, 1000 and 2000 mg/kg of EEPg, respectively. It is noteworthy that 100% of the offspring treated with EEPg showed changes in the ossification process. Thus, it is considered that the EEPg has low maternal toxic potential; it does not alter the reproductive performance of females. However, it is teratogenic and interferes, mainly, in the ossification process, and therefore its use is contraindicated in the gestational period.

Funder

CNPq

FUNDECT

CAPES

UFMS

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

Reference51 articles.

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2. Amides fromPiperas a Diuretic: Behind the Ethnopharmacological Uses ofPiper glabratumKunth;Prando;Evidence-Based Complement. Altern. Med.,2014

3. Anti-inflammatory and toxicological evaluation of essential oil from Piper glabratum leaves;Branquinho;J. Ethnopharmacol.,2017

4. Effects of an ethanolic extract and fractions from Piper glabratum (Piperaceae) leaves on pain and inflammation;Radai;Regul. Toxicol. Pharmacol.,2020

5. Dyer, L.A., and Palmer, A.N. (2004). Piper: Um Gênero Modelo para Estudos de Fitoquímica, Ecologia e Evolução, Kluwer Academic/Plenum.

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