Estudo toxicológico reprodutivo da Azadirachta indica A. Juss. (Neem) em ratas Wistar

A. G. Wanderley; M. M. A. Lyra; J. H. Costa-Silva; C. R. Lima; V. M. Arruda; A. V. Araújo; A. Ribeiro e Ribeiro; A. C. Arruda; M. C. C. A. Fraga; S. S. L. Lafayette

doi:10.32712/2446-4775.2005.24

Toxicological reproductive study of Azadirachta indica A. Juss (Neem) in female Wistar rats

Vol. 1 No. 02 (2005)
53-57
11/10/2013
30/11/2005
https://doi.org/10.32712/2446-4775.2005.24

A. G. Wanderley
M. M. A. Lyra
J. H. Costa-Silva
C. R. Lima
V. M. Arruda
A. V. Araújo
A. Ribeiro e Ribeiro
A. C. Arruda
M. C. C. A. Fraga
S. S. L. Lafayette

Abstract

The effects of the administration of the Azadirachta indica (Neem) seed oil was investigated at the pre-implantation stage in Wistar female rats. Three groups (n = 5-9/group) of female adult rats were treated by oral route from the 1st to the 6th day of pregnancy, in the doses of 1,0 and 2,0 g/kg body weight. On the 20th day of pregnancy, the animals were sacrificed for the evaluation of the following reproductive parameters: number of live and non-live conceptuses; relation offspring/mother; fetal weight; placental and ovarian weight; number of total uterine implantation sites; number of resorption sites; number of ovarian corpora lutea; and number of pre- and post-implantation loss. The results show that there were not statistic differences among control and treated groups on the analyzed parameters, except for the fetal weight, that was significantly reduced in relation to the control group by 10,9 and 12,1%, to the doses of 1,0 and 2,0 g/kg, respectively. In conclusion, the administration of the neem seed oil did not induce anti-implantation effect. However, the reduced fetal weight can indicate fetotoxicity.independent of the method employed.

References

AHMED, N.U.; MOSTOFA, M.; AWAL, M.A. Comparative efficacy of modern anthelmintics with that of neem seeds against gastro-intestinal nematodiasis in sheep. Bangladesh Veterinary Journal, v.28, p.21-23, 1994.
ALADAKATH, R.H.; AHAMED, R.N.; AHAMED, M.; GHOSESAWAR, M.G. Sperm parameters changes induced by Azadirachta indica in albino rats. Journal of Basic and Clinical Physiology and Pharmacology, v.12, p.69-76, 2001.
ALAM, M.M.; SIDDIQUI, M.B.; HUSAIN, W. Treatment of diabetes through herbal drugs in rural Índia. Fitoterapia, v.61, p.240-242, 1990.
ALMEIDA, E.R.; MELO, A.M.; XAVIER, H. Toxicological evaluation of the hydroalcohol extract of the dry leaves of Peumus boldus and boldine in rats. Phytotherapie Research, v.12, n.2, p.99-102, 2000.
ALMEIDA, F.C.G.; LEMONICA, I.P. The toxic effects of Coleus barbatus B. on the different periods of prenancy in rats. Journal of Ethnopharmacology, v.73, p.53-60, 2000.
ASCHER, K.R.S. Nonconventional insecticidal effects of pesticides available from the neem tree, Azadirachta indica. Archives of insect Biochemistry and Physiology, v.22, p.433-449, 1993.
ASIATICO, J.M.; ZOEBISCH, T.G. Control de mosca blanca Bemisia tabaci (Gennadius) en tomate com insecticidas de origen biológico y químico. Manejo Integrado de Plagas, v.24/25, p.1-7, 1992.
BALASENTHIL, S.; ARIVAZHAGAN, S.; RAMACHANDRAN, C.R.; RAMACHANDRAN, V.; NAGINI, S. Chemopreventive potential of neem (Azadirachta indica) on 7,12 - dimethylbenz[ ] anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Journal of Ethnopharmacology, v.67, p.189-195, 1999.
BOEKE, S.J.; BOERSMA, M.G.; ALINK, G.M.; VAN LOON, J.J.; VAN HUIS, A.; DICKE, M.; RIETJENS, I.M.C.M. Safety evaluation of neem (Azadirachta indica) derived pesticides. Journal of Ethnopharmacology, v.94, p.25-41, 2004.
CHANG, C.V.; FELÍCIO, A.C.; REIS, J.E.P.; GUERRA, M.O.; PETERS, V.M. Fetal toxicity of Solanum lycocarpum (Solanaceae) in rats. Journal of Ethnopharmacology, v.81, p.265-269, 2002.
CHATTOPADHYAY, R.R. Possible mechanism of antihyperglycemic effect of Azadirachta indica leaf extract. Part IV. General Pharmacology, v.27, p.367-372, 1996.
CHINNASAMY, N.; HARISHANKAR, N.; KUMAR, P.U.; RUKMINI, C. Toxicological studies on debitterized neem oil (Azadirachta indica). Food and Chemical Toxicology, v.31, p.297-301, 1993.
COUDRIET, D.T.; PRABHAKER, N.; MEYERDIRK, D.E. Sweetpotato whitefly (Homoptera: Aleyrodidae). Effects of neem-seed extract on oviposition and immature stages. Environmental Entomology, v.14, p.776-779, 1985.
CUBILLO, D.; QUIJIJE, R.; LARRIVA, W.; CHACÓN, A.; HILDE, L. Evaluación de la repelencia de varias substancias sobre la mosca blanca Bemisia tabaci (Homoptera: Aleyrodidae). Manejo Integrado de Plagas, v.33, p.26-28, 1994.
DASGUPTA, T.; BANERJEE, S.; YADAVA, P.K.; RAO, A.R. Chemopreventive potential of Azadirachta indica (Neem) leaf extract in murine carcinogenesis model systems. Journal of Ethnopharmacology, v.92, p.23-36, 2004.
DHAR, R.; ZHANG, K.; TALWAR G.P.; GARG, S.; KUMAR, N. Inhibition of the growth and development of asexual and sexual stages of drug-sensitive and resistant strains of the human malaria parasite Plasmodium falciparum by Neem (Azadirachta indica) fractions. Journal of Ethnopharmacology, v.61, p.31-39, 1998.
DHALIWAL, P.K.; ROOP, J.K.; GURAYA, S.S.; DHAWAN, A.K. Antifertility activity of neem-seed oil in cyclic female rats. In: Dhaliwal, G.S., Arora, R., Randhawa, N.S. (Eds.), Ecological Agriculture and Sustainable Development, v.2, Procedings of the International Conference on Ecological Agriculture: Towards Sustainable Development, Chadigard, Índia, p.340-346, 1998.
GARG, G.P.; NIGAM, S.K.; OGLE, C.W. The gastric antiulcer effects of the leaves of the neem tree. Planta Medica, v.59, p.215-217, 1993.
GARG, S.; TALWAR, G.P.; UPADHYAY, S.N. Immunocontraceptive activity guided fractionation and characterization of active constituents of neem (Azadirachta indica) seed extracts. Journal of Ethnopharmacology, v.60, p.235-246, 1998.
GÓMEZ, P.; CUBILLO, D.; MORA, G.A.;HILJE, L. Evaluación de posibles, repelentes de Bemisia tabaci: I. Productos comerciales. Manejo Integrado de Plagas, v.46, p.9-16, 1997.
KAHN, P.K.; AWASTHY, K.S. Cytogenetic toxicity of neem. Food and Chemical Toxicology, v.41, p.1325-1328, 2003.
KASTURI, M.; MANIVANNAN, B.; AHAMED, R.N.; PARVEEN, D.S; PATHAN, K.M. Changes in epididymal structure and function of albino rat treated with Azadirachta indica leaves. Indian Journal of Experimental Biology, v.33, p.725-729, 1995.
KASTURI, M.; AHAMED, R.N.; PATHAN, K.M.; PARVEEN, D.S; MANIVANNAN, B. Effects of Azadirachta indica leaves on the seminal vesicles and ventral prostate in albino rats. Indian Journal of Physiology and Pharmacology, v.41, p.234-260, 1997.
KHILLARE, B; SHRIVASTAV, T.G. Spermicidal activity os Azadirachta indica (neem) leaf extract. Contraception, v.68, p.225-229, 2003.
KOLA, I.; FOLB, P. Chlorpromazine inhibits the mitotic index, cell number, and the formation of blastocyst, and delays implantation of CBA mouse embryos. Journal of Reproduction and Fertility, v.76, p.527-36, 1986.
KVITKO, K.; GIMMLER, M.C. Effects of intergerrimine on the implantation and intrauterine development of mice. Brazilian Journal of Medical and Biological Research, v.29, p.223-7, 1986.
LAL, R.; GANDHI, M.; SANKARANARAYANAN, A.; MATHUR, V.S.; SHARMA, P.L. Antifertility effect of Azadirachta indica oil administered per os to female albino rats on selected days of pregnancy. Fitoterapia, v.58, n.4, p.239-242, 1987.
MALONE, R.A. Pharmacologycal aproache to natural products screening and avaliation. In: New natural products and plant drugs With Pharmacologycal, Biological or Therapeutical Activity. Verlag, Berlin: Springer, p.24-53, 1977.
MILLER, L.C.; TAINTER, M.L. Estimation of the ED50 and error by means of logarithmic probit graph paper. Proceedings of the Society for Experimental Biology and Medicine, v.57, p.261-264, 1944.
MUKHERJEE, S.; TALWAR, G.P. Termination of pregnancy in rodents by oral administration of Praneem, a purified neem seed extract. American Journal of Reproductive Immunology, v.35, p.51-56, 1996.
MUKHERJEE, S.; LOHIYA, N.K.; PAL, R.; SHARMA, M.G.; TALWAR, G.P. Purified Neem (Azadirachta indica) seed extracts (Praneem) abrogate pregnancy in primates. Contraception, v.53, p.375-378, 1996.
NARDO, E.A.B. de; COSTA, A.S.; LOURENÇÃO, A.L. Melia azedarach extract as na antifeedant to Bemisia tabaci (Homoptera: Aleyrodidae). Florida Entomologist, v.80, p.92-94, 1997.
OBASEKI, O.; JEGEDE FANDUNSIN, H.A. The antimalarial activity of Azadirachta indica. Fitoterapia, v.57, p.247-251, 1986.
PAI, M.R.; ACHARYA, L.D.; UDUPA, N. Evaluation of antiplaque activity of Azadirachta indica leaf extract gel - a 6-week clinical study. Journal of Ethnopharmacology, v.90, p.99-103, 2004.
PARVEEN, D.S.; MANIVANNAN, B.; PATHAN, K.M.; KASTURI, M.; AHAMED, R.N. Antispermatic activity of Azadirachta indica leaves in albino rats. Current Science, v.64, p.688-689, 1993.
RAJI, Y.; OGUNWANDE, I.A.; OSADEBE, C.A.; JOHN, G. Effects of Azadirachta indica extract on gastric ulceration and acid secretion in rats. Journal of Ethnopharmacology, v.90, p.167-170, 2004.
SCHMUTTERER, H. Properties and potential of natural pesticides from the neem tree, Azadirachta indica. Annual Review of Entomology, v.35, p.271-297, 1990.
SRIVASTAVA, M.K.; RAIZADA, R.B. Asessment of embryo/fetotoxicity and teratogenecity of azadirachtin in rats. Food and Chemical Toxicology, v.39, p.1023-1027, 2001.
XUAN, T.D.; EIJI, T.; HIROYUKI, T.; MITSUHIRO, M.; KHANH, T.D.; CHUNG, I.M. Evaluation on phytotoxicity of neem (Azadirachta indica A. Juss) to crops and weeds. Crop protection, v.23, p.335-345, 2004.

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Author(s)

A. G. Wanderley
Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Ciências Farmacêuticas Universidade Federal de Pernambuco Laboratório de Farmacologia e Toxicologia Pré-Clínica de Produtos Bioativos Departamento de Fisiologia e Farmacologia, CCB, Universidade Federal de Pernambuco Av. Prof. Moraes Rego s/n, Cidade Universitária, 50670-901 Recife, PE
M. M. A. Lyra
Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Ciências Farmacêuticas Universidade Federal de Pernambuco
J. H. Costa-Silva
Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Ciências Farmacêuticas Universidade Federal de Pernambuco
C. R. Lima
Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Ciências Farmacêuticas Universidade Federal de Pernambuco
V. M. Arruda
Laboratório de Farmacologia e Toxicologia Pré-Clínica de Produtos Bioativos Departamento de Fisiologia e Farmacologia, CCB, Universidade Federal de Pernambuco Av. Prof. Moraes Rego s/n, Cidade Universitária, 50670-901 Recife, PE
A. V. Araújo
Laboratório de Farmacologia e Toxicologia Pré-Clínica de Produtos Bioativos Departamento de Fisiologia e Farmacologia, CCB, Universidade Federal de Pernambuco Av. Prof. Moraes Rego s/n, Cidade Universitária, 50670-901 Recife, PE
A. Ribeiro e Ribeiro
Departamento de Química, Universidade Federal do Pará Belém, PA, Brasil.
A. C. Arruda
Departamento de Química, Universidade Federal do Pará Belém, PA, Brasil.
M. C. C. A. Fraga
Laboratório de Farmacologia e Toxicologia Pré-Clínica de Produtos Bioativos Departamento de Fisiologia e Farmacologia, CCB, Universidade Federal de Pernambuco Av. Prof. Moraes Rego s/n, Cidade Universitária, 50670-901 Recife, PE
S. S. L. Lafayette
Laboratório de Farmacologia e Toxicologia Pré-Clínica de Produtos Bioativos Departamento de Fisiologia e Farmacologia, CCB, Universidade Federal de Pernambuco Av. Prof. Moraes Rego s/n, Cidade Universitária, 50670-901 Recife, PE

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Toxicological reproductive study of Azadirachta indica A. Juss (Neem) in female Wistar rats. Rev Fitos [Internet]. 2005 Nov. 30 [cited 2025 Jan. 11];1(02):53-7. Available from: https://revistafitos.far.fiocruz.br/index.php/revista-fitos/article/view/24

This work is licensed under a Creative Commons Attribution 4.0 International License.

[1] AHMED, N.U.; MOSTOFA, M.; AWAL, M.A. Comparative efficacy of modern anthelmintics with that of neem seeds against gastro-intestinal nematodiasis in sheep. Bangladesh Veterinary Journal, v.28, p.21-23, 1994.

[2] ALADAKATH, R.H.; AHAMED, R.N.; AHAMED, M.; GHOSESAWAR, M.G. Sperm parameters changes induced by Azadirachta indica in albino rats. Journal of Basic and Clinical Physiology and Pharmacology, v.12, p.69-76, 2001.

[3] ALAM, M.M.; SIDDIQUI, M.B.; HUSAIN, W. Treatment of diabetes through herbal drugs in rural Índia. Fitoterapia, v.61, p.240-242, 1990.

[4] ALMEIDA, E.R.; MELO, A.M.; XAVIER, H. Toxicological evaluation of the hydroalcohol extract of the dry leaves of Peumus boldus and boldine in rats. Phytotherapie Research, v.12, n.2, p.99-102, 2000.

[5] ALMEIDA, F.C.G.; LEMONICA, I.P. The toxic effects of Coleus barbatus B. on the different periods of prenancy in rats. Journal of Ethnopharmacology, v.73, p.53-60, 2000.

[6] ASCHER, K.R.S. Nonconventional insecticidal effects of pesticides available from the neem tree, Azadirachta indica. Archives of insect Biochemistry and Physiology, v.22, p.433-449, 1993.

[7] ASIATICO, J.M.; ZOEBISCH, T.G. Control de mosca blanca Bemisia tabaci (Gennadius) en tomate com insecticidas de origen biológico y químico. Manejo Integrado de Plagas, v.24/25, p.1-7, 1992.

[8] BALASENTHIL, S.; ARIVAZHAGAN, S.; RAMACHANDRAN, C.R.; RAMACHANDRAN, V.; NAGINI, S. Chemopreventive potential of neem (Azadirachta indica) on 7,12 - dimethylbenz[ ] anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Journal of Ethnopharmacology, v.67, p.189-195, 1999.

[9] BOEKE, S.J.; BOERSMA, M.G.; ALINK, G.M.; VAN LOON, J.J.; VAN HUIS, A.; DICKE, M.; RIETJENS, I.M.C.M. Safety evaluation of neem (Azadirachta indica) derived pesticides. Journal of Ethnopharmacology, v.94, p.25-41, 2004.

[10] CHANG, C.V.; FELÍCIO, A.C.; REIS, J.E.P.; GUERRA, M.O.; PETERS, V.M. Fetal toxicity of Solanum lycocarpum (Solanaceae) in rats. Journal of Ethnopharmacology, v.81, p.265-269, 2002.

[11] CHATTOPADHYAY, R.R. Possible mechanism of antihyperglycemic effect of Azadirachta indica leaf extract. Part IV. General Pharmacology, v.27, p.367-372, 1996.

[12] CHINNASAMY, N.; HARISHANKAR, N.; KUMAR, P.U.; RUKMINI, C. Toxicological studies on debitterized neem oil (Azadirachta indica). Food and Chemical Toxicology, v.31, p.297-301, 1993.

[13] COUDRIET, D.T.; PRABHAKER, N.; MEYERDIRK, D.E. Sweetpotato whitefly (Homoptera: Aleyrodidae). Effects of neem-seed extract on oviposition and immature stages. Environmental Entomology, v.14, p.776-779, 1985.

[14] CUBILLO, D.; QUIJIJE, R.; LARRIVA, W.; CHACÓN, A.; HILDE, L. Evaluación de la repelencia de varias substancias sobre la mosca blanca Bemisia tabaci (Homoptera: Aleyrodidae). Manejo Integrado de Plagas, v.33, p.26-28, 1994.

[15] DASGUPTA, T.; BANERJEE, S.; YADAVA, P.K.; RAO, A.R. Chemopreventive potential of Azadirachta indica (Neem) leaf extract in murine carcinogenesis model systems. Journal of Ethnopharmacology, v.92, p.23-36, 2004.

[16] DHAR, R.; ZHANG, K.; TALWAR G.P.; GARG, S.; KUMAR, N. Inhibition of the growth and development of asexual and sexual stages of drug-sensitive and resistant strains of the human malaria parasite Plasmodium falciparum by Neem (Azadirachta indica) fractions. Journal of Ethnopharmacology, v.61, p.31-39, 1998.

[17] DHALIWAL, P.K.; ROOP, J.K.; GURAYA, S.S.; DHAWAN, A.K. Antifertility activity of neem-seed oil in cyclic female rats. In: Dhaliwal, G.S., Arora, R., Randhawa, N.S. (Eds.), Ecological Agriculture and Sustainable Development, v.2, Procedings of the International Conference on Ecological Agriculture: Towards Sustainable Development, Chadigard, Índia, p.340-346, 1998.

[18] GARG, G.P.; NIGAM, S.K.; OGLE, C.W. The gastric antiulcer effects of the leaves of the neem tree. Planta Medica, v.59, p.215-217, 1993.

[19] GARG, S.; TALWAR, G.P.; UPADHYAY, S.N. Immunocontraceptive activity guided fractionation and characterization of active constituents of neem (Azadirachta indica) seed extracts. Journal of Ethnopharmacology, v.60, p.235-246, 1998.

[20] GÓMEZ, P.; CUBILLO, D.; MORA, G.A.;HILJE, L. Evaluación de posibles, repelentes de Bemisia tabaci: I. Productos comerciales. Manejo Integrado de Plagas, v.46, p.9-16, 1997.

[21] KAHN, P.K.; AWASTHY, K.S. Cytogenetic toxicity of neem. Food and Chemical Toxicology, v.41, p.1325-1328, 2003.

[22] KASTURI, M.; MANIVANNAN, B.; AHAMED, R.N.; PARVEEN, D.S; PATHAN, K.M. Changes in epididymal structure and function of albino rat treated with Azadirachta indica leaves. Indian Journal of Experimental Biology, v.33, p.725-729, 1995.

[23] KASTURI, M.; AHAMED, R.N.; PATHAN, K.M.; PARVEEN, D.S; MANIVANNAN, B. Effects of Azadirachta indica leaves on the seminal vesicles and ventral prostate in albino rats. Indian Journal of Physiology and Pharmacology, v.41, p.234-260, 1997.

[24] KHILLARE, B; SHRIVASTAV, T.G. Spermicidal activity os Azadirachta indica (neem) leaf extract. Contraception, v.68, p.225-229, 2003.

[25] KOLA, I.; FOLB, P. Chlorpromazine inhibits the mitotic index, cell number, and the formation of blastocyst, and delays implantation of CBA mouse embryos. Journal of Reproduction and Fertility, v.76, p.527-36, 1986.

[26] KVITKO, K.; GIMMLER, M.C. Effects of intergerrimine on the implantation and intrauterine development of mice. Brazilian Journal of Medical and Biological Research, v.29, p.223-7, 1986.

[27] LAL, R.; GANDHI, M.; SANKARANARAYANAN, A.; MATHUR, V.S.; SHARMA, P.L. Antifertility effect of Azadirachta indica oil administered per os to female albino rats on selected days of pregnancy. Fitoterapia, v.58, n.4, p.239-242, 1987.

[28] MALONE, R.A. Pharmacologycal aproache to natural products screening and avaliation. In: New natural products and plant drugs With Pharmacologycal, Biological or Therapeutical Activity. Verlag, Berlin: Springer, p.24-53, 1977.

[29] MILLER, L.C.; TAINTER, M.L. Estimation of the ED50 and error by means of logarithmic probit graph paper. Proceedings of the Society for Experimental Biology and Medicine, v.57, p.261-264, 1944.

[30] MUKHERJEE, S.; TALWAR, G.P. Termination of pregnancy in rodents by oral administration of Praneem, a purified neem seed extract. American Journal of Reproductive Immunology, v.35, p.51-56, 1996.

[31] MUKHERJEE, S.; LOHIYA, N.K.; PAL, R.; SHARMA, M.G.; TALWAR, G.P. Purified Neem (Azadirachta indica) seed extracts (Praneem) abrogate pregnancy in primates. Contraception, v.53, p.375-378, 1996.

[32] NARDO, E.A.B. de; COSTA, A.S.; LOURENÇÃO, A.L. Melia azedarach extract as na antifeedant to Bemisia tabaci (Homoptera: Aleyrodidae). Florida Entomologist, v.80, p.92-94, 1997.

[33] OBASEKI, O.; JEGEDE FANDUNSIN, H.A. The antimalarial activity of Azadirachta indica. Fitoterapia, v.57, p.247-251, 1986.

[34] PAI, M.R.; ACHARYA, L.D.; UDUPA, N. Evaluation of antiplaque activity of Azadirachta indica leaf extract gel - a 6-week clinical study. Journal of Ethnopharmacology, v.90, p.99-103, 2004.

[35] PARVEEN, D.S.; MANIVANNAN, B.; PATHAN, K.M.; KASTURI, M.; AHAMED, R.N. Antispermatic activity of Azadirachta indica leaves in albino rats. Current Science, v.64, p.688-689, 1993.

[36] RAJI, Y.; OGUNWANDE, I.A.; OSADEBE, C.A.; JOHN, G. Effects of Azadirachta indica extract on gastric ulceration and acid secretion in rats. Journal of Ethnopharmacology, v.90, p.167-170, 2004.

[37] SCHMUTTERER, H. Properties and potential of natural pesticides from the neem tree, Azadirachta indica. Annual Review of Entomology, v.35, p.271-297, 1990.

[38] SRIVASTAVA, M.K.; RAIZADA, R.B. Asessment of embryo/fetotoxicity and teratogenecity of azadirachtin in rats. Food and Chemical Toxicology, v.39, p.1023-1027, 2001.

[39] XUAN, T.D.; EIJI, T.; HIROYUKI, T.; MITSUHIRO, M.; KHANH, T.D.; CHUNG, I.M. Evaluation on phytotoxicity of neem (Azadirachta indica A. Juss) to crops and weeds. Crop protection, v.23, p.335-345, 2004.