Toxicological aspects of ivermectin: a study of the effects on the liver morphology of pregnant rats
Keywords:Ivermectin; Liver; Rats.
Ivermectin, the pharmacological principle of a veterinary drug has an antiparasitic effect against endo and ectoparasites, it is widely used in veterinary practice. This drug is biotransformed in the liver, resulting in 3 metabolites, the most important being 24-hydroxy-methyl-dihydroavermectin B1. The liver is essential in regulating metabolism, in the synthesis of certain proteins, serving as a storage site for certain vitamins and iron, degrading certain hormones and inactivating and excreting certain drugs and toxins. Therefore, this study aimed to evaluate the morphology of the livers of pregnant rats treated with ivermectin. For this purpose, 30 albino rats were used, which were divided into 3 groups of 10 animals. The annimals were placed to mate and after the detection of pregnancy, the presence of sperm in the vaginal smear performed on the morning of the following day, being thus designated the first day of pregnancy, each animal was treated with ivermectin, in the dose corresponding to each group for 18 days, with administration every 3 (three) days, totaling 6 administrations. After this period, the liver was collected, weighed on an analytical balance and processed for light microscopy. The analysis of the relative weight of the livers of pregnant and non-pregnant rats did not reveal any significant difference between the experimental groups, where treatment with ivermectin at doses of 4.0 and 8.0 mg / kg did not alter the relative mass of the liver, nor did it show changes in color, texture, consistency and bleeding. Regarding the study through light microscopy, histopathological changes were not observed.
Amann, R.P. & Jonhson, A.D. (1970). Sperm production rates. Academic, 1, 433-482.
Booth, N. H. & Mcdonald, L. E. (1992). Farmacologia e terapêutica em veterinária (v 997). Ed. Guanabara.
Cormack, D. H. (2003). Fundamentos de Histologia. (2a ed.).
Chiu, S. H., Sestokas, E. L. E. N. A., Taub, R., Buhs, R. P., Green, M. A. R. I. L. Y. N., Sestokas, R. U. T. A., & Jacob, T. A. (1986). Metabolic disposition of ivermectin in tissues of cattle, sheep, and rats. Drug Metabolism and Disposition, 14(5), 590-600.
Delayte, E. H., Otsuka, M., Larsson, C. E., & Castro, R. C. C. (2006). Eficácia das lactonas macrocíclicas sistêmicas (ivermectina e moxidectina) na terapia da demodicidose canina generalizada. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, 58(1), 31-38.
Delgado, F. E., Lima, S. W., Bello, A. C., Domingues, L. N., Wanderley, R. P., Leite, P. V., & Leite, R. C. (2009). Cattle helminthiasis: farmers perception in Minas Gerais, Brazil. Revista brasileira de parasitologia veterinaria= Brazilian journal of veterinary parasitology: Orgao Oficial do Colegio Brasileiro de Parasitologia Veterinaria, 18(3), 29-33.
Fausto, N., Campbell, J. S., & Riehle, K. J. (2006). Liver regeneration. Hepatology 43: S45–S53.
Geary, T. G. (2005). Ivermectin 20 years on: maturation of a wonder drug. Trends in parasitology, 21(11), 530-532.
Gupta, R. C. (2007). Ivermectin and selamectin. In Veterinary Toxicology (pp. 508-513). Academic Press.
Junqueira, L. C., & Carneiro, J. (2004). Histologia básica. (10a ed.). Rio de Janeiro.
Junqueira, L. C., & Carneiro J. (2013). Histologia Básica. (12a ed.). Rio de Janeiro.
Khoja, S., Huynh, N., Warnecke, A. M., Asatryan, L., Jakowec, M. W., & Davies, D. L. (2018). Preclinical evaluation of avermectins as novel therapeutic agents for alcohol use disorders. Psychopharmacology, 235(6), 1697-1709.
Laing, R., Gillan, V., & Devaney, E. (2017). Ivermectin–old drug, new tricks? Trends in parasitology, 33(6), 463-472.
Lankas, G. R., Minsker, D. H., & Robertson, R. T. (1989). Effects of ivermectin on reproduction and neonatal toxicity in rats. Food and chemical toxicology, 27(8), 523-529.
Lobato, V., Rath, S., & Reyes, F. G. (2004). Considerações sobre a presença de ivermectina em alimentos de origem animal. Rev. bras. toxicol, 27-38.
Medeiros, J. P., de Moura Estevão, L. R., Baratella-Evêncio, L., dos Santos, J. M., Simões, R. S., de Jesus Simões, M., & Evêncio-Neto, J. (2008). Efeito da ivermectina sobre a ciclicidade, gestação e desenvolvimento neonatal em ratos. Brazilian Journal of Veterinary Research and Animal Science, 45(6), 472-480.
Möller, V. M., Dallegrave, E., Coelho, R., Pereira, J., & Langeloh, A. (2003). Efeitos da ivermectina (Ivomec® 1% injetável) administrada a ratas Wistar durante o período de organogênese. Brazilian Journal of Veterinary Research and Animal Science, 40(5), 328-333.
Omura, S. (2008). Ivermectina: 25 anos e continua forte. Jornal internacional de agentes antimicrobianos, 31 (2), 91-98.
Pereira,A. S., Shitsuka, D. M., Parreira, F. J., & Shitsuka, R. (2018). Metodologia da pesquisa científica. UAB/NTE/UFSM. https://repositorio.ufsm.br/bitstream/handle/1/15824/Lic_Computacao_Metodologia-Pesquisa-Cientifica.pdf?sequence=1
Poul, J. M. (1988). Effects of perinatal ivermectin exposure on behavioral development of rats. Neurotoxicology and teratology, 10(3), 267-272.
Robert, M. B., & Matthew, N. L. Ivermectin. Oral range-finding study in pregnant rats. California Departament of Food and Agriculture Medical Toxicology. Fisiologia. (3a ed.), Rio de Janeiro: Guanabara Koogan, 1996. 988p.
Sanford, S. E., Rehmtulla, A. J., & Josephson, G. K. (1988). Ivermectin overdose and toxicosis in neonatal pigs. The Canadian Veterinary Journal, 29(9), 735.
Sutherland, I. H., & Campbell, W. C. (1990). Development, pharmacokinetics and mode of action of ivermectin. Acta Leidensia, 59(1-2), 161-168.
Spinosa, H. D. S., Górniak, S. L., & Bernardi, M. M. (1999). Farmacologia aplicada à medicina veterinária. Rio de Janeiro.
Temple, W. A. & Smithdiante, M. A. Ivermectin. New Castle, United Kingdom: International Programme on Chemical Safety, 1994. PIM 292.
Zorn, A. M. Liver development. StemBook. The Stem Cell Research Community. 2008.
How to Cite
Copyright (c) 2021 Juliana Pinto de Medeiros; Rodrigo Reges dos Santos Silva; Leandro Paes de Brito; Marcos Aurélio Santos da Costa; Daniela Maria Santos Falcão; Maria Eduarda da Silva; Fernanda das Chagas Ângelo Mendes Tenório; Bruno Mendes Tenório; Carina Scanoni Maia; Luciana Maria Silva de Seixas Maia; Joaquim Evêncio Neto
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.