PMID- 36963474
OWN - NLM
STAT- MEDLINE
DCOM- 20230411
LR  - 20230411
IS  - 1872-7573 (Electronic)
IS  - 0378-8741 (Linking)
VI  - 310
DP  - 2023 Jun 28
TI  - Genotoxicity and maternal-fetal safety of the dried extract of leaves of 
      Azadirachta indica A. Juss (Meliaceae) in Wistar rats.
PG  - 116403
LID - S0378-8741(23)00271-4 [pii]
LID - 10.1016/j.jep.2023.116403 [doi]
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Azadirachta indica A. Juss (Meliaceae), popularly 
      known as "neem", is used for the treatment of rheumatism, cancer, ulcers, 
      diabetes, respiratory problems, among others. This species is present on six 
      continents and contains more than 400 bioactive compounds. Practically all parts 
      of the plant are used in the treatment of diseases. Although it is widely used, 
      no study has evaluated the safety of this species throughout the gestational 
      period in Wistar rats. AIM OF THE STUDY: To evaluate the genotoxicity and the 
      effect of treatment with dried extract of leaves of Azadirachta indica on 
      maternal toxicity and fetal development. MATERIALS AND METHODS: The dried extract 
      of leaves of A. indica was obtained by spray drying after percolation of the 
      plant material in 30% ethanol (w/w). The total flavonoids and rutin contents of 
      the extract were determined by spectrophotometric method and HPLC-DAD, 
      respectively. Pregnant Wistar rats (n = 40) were divided into four groups 
      (n = 10/group): one control and three groups treated with dried extract of leaves 
      of A. indica at doses of 300, 600 or 1200 mg/kg. Treatments were carried out from 
      gestational day (GD) 0-20. During gestation, clinical signs of toxicity, weight 
      gain, feed and water consumption of the dams were evaluated. On GD 21, rats were 
      euthanized and cardiac blood was collected. Liver, kidneys, lung, heart, uterus, 
      ovaries and bone marrow were collected. Reproductive performance parameters, 
      histopathological analysis, biochemistry and genotoxicity were evaluated. Fetuses 
      were evaluated for external morphology, skeletal and visceral changes. RESULTS: 
      The total flavonoid content of the extract ranged from 2.64 to 3.01%, and the 
      rutin content was 1.07%. There was no change in body mass gain, food and water 
      consumption between the evaluated groups. There was also no difference between 
      the groups in terms of biochemical parameters, reproductive performance, 
      histopathological analysis of the mother's organs and genotoxicity. Supernumerary 
      ossification sites of the sternum were observed, and other skeletal and visceral 
      alterations were not significant. CONCLUSIONS: The treatment did not induce 
      maternal toxicity, it was neither embryotoxic nor fetotoxic. The extract was not 
      potentially genotoxic, and at a dose of 1200 mg/kg, it caused changes in the 
      ossification of the sternum.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Ramalho, Carlos Eduardo Lacerda
AU  - Ramalho CEL
AD  - Programa de Pos-Graduacao em Ciencias Aplicadas a Produtos para Saude (CAPS). 
      Universidade Estadual de Goias. Campus Anapolis de Ciencias Exatas e 
      Tecnologicas, Anapolis, Goias, Brazil; Laboratorio de Pesquisa, Desenvolvimento & 
      Inovacao de Produtos da Biodiversidade. Universidade Estadual de Goias. Campus 
      Anapolis de Ciencias Exatas e Tecnologicas, Anapolis, Goias, Brazil.
FAU - Reis, Diego Dos Santos
AU  - Reis DDS
AD  - Laboratorio de Farmacologia e Toxicologia de Produtos Naturais e Sinteticos. 
      Universidade Estadual de Goias. Campus Anapolis de Ciencias Exatas e 
      Tecnologicas, Anapolis, Goias, Brazil.
FAU - Caixeta, Graziele Alicia Batista
AU  - Caixeta GAB
AD  - Programa de Pos-Graduacao em Ciencias Aplicadas a Produtos para Saude (CAPS). 
      Universidade Estadual de Goias. Campus Anapolis de Ciencias Exatas e 
      Tecnologicas, Anapolis, Goias, Brazil; Laboratorio de Farmacologia e Toxicologia 
      de Produtos Naturais e Sinteticos. Universidade Estadual de Goias. Campus 
      Anapolis de Ciencias Exatas e Tecnologicas, Anapolis, Goias, Brazil.
FAU - Oliveira, Micaelle Cristina de
AU  - Oliveira MC
AD  - Laboratorio de Farmacologia e Toxicologia de Produtos Naturais e Sinteticos. 
      Universidade Estadual de Goias. Campus Anapolis de Ciencias Exatas e 
      Tecnologicas, Anapolis, Goias, Brazil.
FAU - Silva, Danielle Milany Fernandes da
AU  - Silva DMFD
AD  - Laboratorio de Farmacologia e Toxicologia de Produtos Naturais e Sinteticos. 
      Universidade Estadual de Goias. Campus Anapolis de Ciencias Exatas e 
      Tecnologicas, Anapolis, Goias, Brazil.
FAU - Cruvinel, Wilson de Melo
AU  - Cruvinel WM
AD  - Escola de Ciencias Medicas e da Vida, Pontificia Universidade Catolica de Goias, 
      Goiania, Goias, Brazil.
FAU - Teofilo, Monatha Nayara Guimaraes
AU  - Teofilo MNG
AD  - Escola de Ciencias Medicas e da Vida, Pontificia Universidade Catolica de Goias, 
      Goiania, Goias, Brazil.
FAU - Gomes, Clayson Moura
AU  - Gomes CM
AD  - Escola de Ciencias Medicas e da Vida, Pontificia Universidade Catolica de Goias, 
      Goiania, Goias, Brazil.
FAU - Sousa, Priscilla Abdala de
AU  - Sousa PA
AD  - Universidade de Rio Verde, Goiania, Goias, Brazil.
FAU - Soares, Leiza Fagundes
AU  - Soares LF
AD  - Programa de Pos-Graduacao em Ciencias Aplicadas a Produtos para Saude (CAPS). 
      Universidade Estadual de Goias. Campus Anapolis de Ciencias Exatas e 
      Tecnologicas, Anapolis, Goias, Brazil; Laboratorio de Pesquisa, Desenvolvimento & 
      Inovacao de Produtos da Biodiversidade. Universidade Estadual de Goias. Campus 
      Anapolis de Ciencias Exatas e Tecnologicas, Anapolis, Goias, Brazil.
FAU - Melo, Anielly Monteiro de
AU  - Melo AM
AD  - Laboratorio de Pesquisa, Desenvolvimento & Inovacao de Produtos da 
      Biodiversidade. Universidade Estadual de Goias. Campus Anapolis de Ciencias 
      Exatas e Tecnologicas, Anapolis, Goias, Brazil.
FAU - Rocha, Jamira Dias
AU  - Rocha JD
AD  - Laboratorio de Biotecnologia. Universidade Estadual de Goias, Campus Anapolis de 
      Ciencias Exatas e Tecnologicas, Anapolis, Goias, Brazil.
FAU - Bailao, Elisa Flavia Luiz Cardoso
AU  - Bailao EFLC
AD  - Laboratorio de Biotecnologia. Universidade Estadual de Goias, Campus Anapolis de 
      Ciencias Exatas e Tecnologicas, Anapolis, Goias, Brazil.
FAU - Amaral, Vanessa Cristiane Santana
AU  - Amaral VCS
AD  - Programa de Pos-Graduacao em Ciencias Aplicadas a Produtos para Saude (CAPS). 
      Universidade Estadual de Goias. Campus Anapolis de Ciencias Exatas e 
      Tecnologicas, Anapolis, Goias, Brazil; Laboratorio de Farmacologia e Toxicologia 
      de Produtos Naturais e Sinteticos. Universidade Estadual de Goias. Campus 
      Anapolis de Ciencias Exatas e Tecnologicas, Anapolis, Goias, Brazil.
FAU - Paula, Joelma Abadia Marciano de
AU  - Paula JAM
AD  - Programa de Pos-Graduacao em Ciencias Aplicadas a Produtos para Saude (CAPS). 
      Universidade Estadual de Goias. Campus Anapolis de Ciencias Exatas e 
      Tecnologicas, Anapolis, Goias, Brazil; Laboratorio de Pesquisa, Desenvolvimento & 
      Inovacao de Produtos da Biodiversidade. Universidade Estadual de Goias. Campus 
      Anapolis de Ciencias Exatas e Tecnologicas, Anapolis, Goias, Brazil. Electronic 
      address: joelma.paula@ueg.br.
LA  - eng
PT  - Journal Article
DEP - 20230322
PL  - Ireland
TA  - J Ethnopharmacol
JT  - Journal of ethnopharmacology
JID - 7903310
RN  - 0 (Plant Extracts)
RN  - 5G06TVY3R7 (Rutin)
SB  - IM
MH  - Pregnancy
MH  - Female
MH  - Rats
MH  - Animals
MH  - *Azadirachta/chemistry
MH  - *Meliaceae
MH  - Rats, Wistar
MH  - Plant Extracts/pharmacology
MH  - Rutin
MH  - DNA Damage
MH  - Plant Leaves/chemistry
OTO - NOTNLM
OT  - Congenital anomalies
OT  - Developmental toxicity
OT  - Neem
OT  - Reproductive toxicity
OT  - Rutin
OT  - Total flavonoids
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/03/25 06:00
MHDA- 2023/04/11 06:41
CRDT- 2023/03/24 20:27
PHST- 2023/01/31 00:00 [received]
PHST- 2023/03/07 00:00 [revised]
PHST- 2023/03/17 00:00 [accepted]
PHST- 2023/04/11 06:41 [medline]
PHST- 2023/03/25 06:00 [pubmed]
PHST- 2023/03/24 20:27 [entrez]
AID - S0378-8741(23)00271-4 [pii]
AID - 10.1016/j.jep.2023.116403 [doi]
PST - ppublish
SO  - J Ethnopharmacol. 2023 Jun 28;310:116403. doi: 10.1016/j.jep.2023.116403. Epub 
      2023 Mar 22.