Hepatic and renal evaluation in rats submitted to chronic administration of botulinum toxin tip A in the submandibular salivary gland

Authors

DOI:

https://doi.org/10.33448/rsd-v11i10.32423

Keywords:

Neurotoxin; Liver; Kidney; Toxicity; Histopathology.

Abstract

Botulinum toxin type A (BTX-A) has been used as one of the treatment options to control sialorrhea, however its systemic effects after chronic treatment are not yet known. Therefore, the objective was to evaluate histopathological alterations of the hepatic and renal parenchyma of rats chronically treated with botulinum toxin type A injection in the submandibular-sublingual complex. Twenty-one adult Wistar rats were divided into three groups with 7 animals each: control; groups BTX-12 and BTX-35, which received 3 intercalated applications of BTX-A. The BTX-12 and BTX-35 groups were analyzed at 12 and 35 days after treatment, respectively. Histopathological and histomorphometric analyzes of the liver and kidney of all animals in the groups were performed. In the liver, histopathological changes were observed characterized by hypertrophy of hepatocytes, pyknosis, centrilobular degeneration and lymphohistiocytic, neutrophilic infiltrate and in the kidneys, decreased capsular space, glomerulopathies and degenerations in nephrons and convoluted tubules were observed. Histomorphometry revealed a reduction in the size of the hepatocyte nuclei and also of the renal glomerulus. Therefore, it can be suggested that botulinum toxin type A administered to rats for the treatment of sialorrhea has hepatotoxic and nephrotoxic potential.

References

Al-Saleem, F. H., Sharma, R., Puligedda, R. D., Elias, M., Kattala, C. D., Simon, P. M., ... &Dessain, S. K. (2017). RBC adherence of immune complexes containingbotulinumtoxin improves neutralization and macrophageuptake. Toxins, 9(5), 173.

Al-Qadhi, G., Mohammed, M. M. A., Al-Ak'hali, M., & Al-Moraissi, E. A. (2021). Khat (CathaEdulisForsk) inducedapoptosis and cytotoxicity in culturedcells: A scoping review. Heliyon, 7(12), e08466.

Arellano-Saldaña, M. E., Rodríguez-Silverio, J., Morales-Osorio, M. G., & de la Luz Arenas-Sordo, M. (2014). Eficacia clínica de laaplicación de toxina botulínica tipo A enlasglándulas submaxilares para eltratamiento de lasialorrea profusa en pacientes pediátricos con parálisis cerebral. InvestigaciónenDiscapacidad, 3(3), 101-105.

Bhaijee, F., & Anders, R. A. (2017). Drug-inducedhepatitis: histologicclues to a difficult diagnosis. DiagnosticHistopathology, 23(12), 559-562.

Botox®. [Bula]. (2015). Bula para o profissional de Saúde. 32 f. Farmacêutico Responsá¬vel: Dra. Elizabeth Mesquita – CRF/SP nº 14.337. Westport, Irlanda: AllerganPharmaceuticalsIreland. https://allergan-web-cdn-prod.azureedge.net/allerganbrazil/allerganbrazil/media/allergan-brazil/botox_bula_paciente.pdf.

Couser, W. G., & Johnson, R. J. (2014). The etiology of glomerulonephritis: roles of infection and autoimmunity. Kidneyinternational, 86(5), 905-914.

Cristália. (2006). Produtos Químicos Farmacêuticos LTDA. Prosigne® - Mitos eVerda-des. 12f. http://www.2cristalia.com.br/prosigne/mitos_e_verdades.pdf.

Del Carmen Contini, M., Fabro, A., Millen, N., Benmelej, A., &Mahieu, S. (2017). Adverse effects in kidneyfunction, antioxidant systems and histopathology in ratsreceivingmonosodiumglutamate diet. Experimental and ToxicologicPathology, 69(7), 547-556.

Eadon, M. T., Schwantes-An, T. H., Phillips, C. L., Roberts, A. R., Greene, C. V., Hallab, A., ... &Moorthi, R. N. (2020). Kidneyhistopathology and prediction of kidneyfailure: a retrospectivecohort study. American Journal of Kidney Diseases, 76(3), 350-360.

El Hidan, M. A., Touloun, O., El Hiba, O., Chait, A., Hafid, J. E., &Boumezzough, A. (2015). Behavioral, histopathological and biochemicalimpairments observed in miceenvenomed by the scorpion: Hottentotagentili (Pallary, 1924). Toxicon, 103, 19-29.

El-Neweshy, M. S., & El-Sayed, Y. S. (2011). Influence of vitamin C supplementation on lead-inducedhistopathologicalalterations in male rats. Experimental and ToxicologicPathology, 63(3), 221-227.

Iorga, A., & Dara, L. (2019). Cell death in drug-inducedliverinjury. Advances in Pharmacology, 85, 31-74.

Jacoby-Alner, T. E., Stephens, N., Davern, K. M., Balmer, L., Brown, S. G. A., &Swindells, K. (2011). Histopathological analysis and in situ localisation of Australiantigersnakevenom in two clinicallyenvenomeddomesticanimals. Toxicon, 58(4), 304-314.

Jiang, H., Xiang, Y., Hu, X., & Cai, H. (2014). Acrylamideinhibitsnervesproutinginduced by botulinumtoxintype A. Neural Regeneration Research, 9(16), 1525.

Jost, W. H. (2016). The option of sonographicguidance in Botulinumtoxininjection for drooling in Parkinson’s disease. Journal of Neural Transmission, 123(1), 51-55.

Kaartinen, K., Safa, A., Kotha, S., Ratti, G., &Meri, S. (2019, October). Complementdysregulation in glomerulonephritis. In Seminars in immunology (Vol. 45, p. 101331). Academic Press.

Kimura, H., Takeda, A., Kikukawa, T., Hasegawa, I., Mino, T., Uchida-Kobayashi, S., ... &Itoh, Y. (2020). Liverinjury after methylprednisolone pulse therapy in multiple sclerosis is usually due to idiosyncratic drug-inducedtoxicityrather than autoimmunehepatitis. Multiple Sclerosis and Related Disorders, 42, 102065.

Grudzinski, I. P., Ruzycka, M., Cieszanowski, A., Szeszkowski, W., Badurek, I., Malkowska, A., &Bamburowicz-Klimkowska, M. (2019). MRI-based preclinical discovery of DILI: A lesson from paracetamol-inducedhepatotoxicity. RegulatoryToxicology and Pharmacology, 108, 104478.

Manrique, D. (2005). Application of type A botulinumtoxin to reduce saliva in amyotrophicsclerosis lateral. Rev Bras Otorrinolaringol, 71(5), 566-9.

Møller, E., Karlsborg, M., Bardow, A., Lykkeaa, J., Nissen, F. H., &Bakke, M. (2011). Treatment of severedrooling with botulinumtoxin in amyotrophic lateral sclerosis and Parkinson's disease: efficacy and possiblemechanisms. Acta OdontologicaScandinavica, 69(3), 151-157.

Möller Bredo, R., &Vazquez Odo, N. (2011). Anatomía del hígado de la rata Wistar (Rattusnorvegicus). International Journal of Morphology, 29(1), 76-79.

Prosigne®. [Bula]. (2013). Bula para o profissional de Saúde. 13 f. Farmacêutico Res¬ponsável: Dr. José Carlos Módolo – CRF/SP nº 10.446. Lanzhou, Gansu, República Popular da China: Lanzhou Institute of Biological Products. https://www.cristalia.com.br/arquivos_medicamentos/148/Prosigne_Bula_Profissional.pdf

Rhéaume, C., Cai, B. B., Wang, J., Fernández-Salas, E., Aoki, K. R., Francis, J., &Broide, R. S. (2015). A highly specific monoclonal antibody for botulinumneurotoxintype A-cleaved SNAP25. Toxins, 7(7), 2354-2370.

Schyman, P., Printz, R. L., AbdulHameed, M. D. M., Estes, S. K., Shiota, C., Shiota, M., &Wallqvist, A. (2020). A toxicogenomic approach to assesskidneyinjuryinduced by mercuricchloride in rats. Toxicology, 442, 152530.

Shan, Z & Ju, C. (2019). Macrófagos hepáticos na lesão hepática induzida por drogas. Pesquisa do fígado, v 3, p 170-175.

Selmi, S., Rtibi, K., Grami, D., Sebai, H., &Marzouki, L. (2018). Malathion, an organophosphateinsecticide, provokesmetabolic, histopathologic and molecular disorders in liver and kidney in prepubertal male mice. Toxicologyreports, 5, 189-195.

Simpson, L. (2013). The life history of a botulinumtoxinmolecule. Toxicon, 68, 40-59.

Thakkar, S., Li, T., Liu, Z., Wu, L., Roberts, R., & Tong, W. (2020). Drug-inducedliverinjuryseverity and toxicity (DILIst): binaryclassification of 1279 drugs by human hepatotoxicity. Drug discovery today, 25(1), 201-208.

Tolosa, E. M. C. D., Rodrigues, C. J., Behmer, O. A., & Freitas Neto, A. G. D. (2003). Manual de técnicas para histologia: normal e patológica.

Un, H., Ugan, R. A., Kose, D., Bayir, Y., Cadirci, E., Selli, J., &Halici, Z. (2020). A novel effect of Aprepitant: Protection for cisplatin-inducednephrotoxicity and hepatotoxicity. European journal of pharmacology, 880, 173168.

Wallig, M. A., Bolon, B., Haschek, W. M., &Rousseaux, C. G. Fundamentals of Toxicologic Pathology. 3 Ed. United States, Elsevier, 2018.

Wolverton, S. E &Vuppalanchi, R. Hepatotoxicity of Dermatologic Drug Therapy. Comprehensive Dermatologic Drug Therapy, p 677-688, 2020.

Zheng, N., Gu, Y., Hong, Y., Sheng, L., Chen, L., Zhang, F., ... & Li, H. (2020). Vancomycinpretreatmentattenuatesacetaminophen-inducedliverinjury through 2-hydroxybutyric acid. Journal of Pharmaceutical Analysis, 10(6), 560-570.

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Published

26/07/2022

How to Cite

SILVA, J. S. de L. M. .; SOUZA, F. de A. L. .; BARROS , M. E. G. de; LEONEL , A. C. L. da S. .; EVÊNCIO, L. B. .; REGUEIRA , L. S. .; EVÊNCIO NETO , J. .; OLIVEIRA, J. B. de .; MEDEIROS, J. P. de . Hepatic and renal evaluation in rats submitted to chronic administration of botulinum toxin tip A in the submandibular salivary gland. Research, Society and Development, [S. l.], v. 11, n. 10, p. e148111032423, 2022. DOI: 10.33448/rsd-v11i10.32423. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/32423. Acesso em: 5 nov. 2024.

Issue

Section

Health Sciences