A new 3D model of L929 fibroblasts microtissues uncovers the effects of Bothrops erythromelas venom and its antivenom.

Autor: Andrade FRS; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St, 1127, Fortaleza, CE, 60.430-275, Brazil. rhaynan2@gmail.com.; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St, 1000, Fortaleza, CE, 60.430-275, Brazil. rhaynan2@gmail.com., da Silva EL; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St, 1127, Fortaleza, CE, 60.430-275, Brazil.; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St, 1000, Fortaleza, CE, 60.430-275, Brazil., Marinho AD; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St, 1127, Fortaleza, CE, 60.430-275, Brazil.; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St, 1000, Fortaleza, CE, 60.430-275, Brazil., Oliveira ACX; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St, 1000, Fortaleza, CE, 60.430-275, Brazil.; Department of Morphology, School of Medicine, Postgraduate Program in Morphological Science, Federal University of Ceará, Delmiro de Farias St., Fortaleza, CE, 60.430-170, Brazil., Sánchez-Porras D; Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, and Instituto de Investigación Biosanitaria, Ibs.GRANADA, Granada, Spain., Bermejo-Casares F; Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, and Instituto de Investigación Biosanitaria, Ibs.GRANADA, Granada, Spain., Montenegro RC; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St, 1127, Fortaleza, CE, 60.430-275, Brazil.; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St, 1000, Fortaleza, CE, 60.430-275, Brazil., Carriel V; Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, and Instituto de Investigación Biosanitaria, Ibs.GRANADA, Granada, Spain., Monteiro HSA; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St, 1127, Fortaleza, CE, 60.430-275, Brazil.; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St, 1000, Fortaleza, CE, 60.430-275, Brazil., Jorge RJB; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St, 1127, Fortaleza, CE, 60.430-275, Brazil.; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St, 1000, Fortaleza, CE, 60.430-275, Brazil.; Department of Morphology, School of Medicine, Postgraduate Program in Morphological Science, Federal University of Ceará, Delmiro de Farias St., Fortaleza, CE, 60.430-170, Brazil.
Jazyk: angličtina
Zdroj: Archives of toxicology [Arch Toxicol] 2024 Oct; Vol. 98 (10), pp. 3503-3512. Date of Electronic Publication: 2024 Jul 15.
DOI: 10.1007/s00204-024-03824-0
Abstrakt: In Brazil, around 80% of snakebites are caused by snakes of the genus Bothrops. A three-dimensional culture model was standardized and used to perform treatments with Bothrops erythromelas venom (BeV) and its antivenom (AV). The MRC-5 and L929 cell lines were cultured at increasing cell densities. Morphometric parameters were evaluated through images obtained from an inverted microscope: solidity, circularity, and Feret diameter. L929 microtissues (MT) showed better morphometric data, and thus they were used for further analysis. MT viability was assessed using the acridine orange and ethidium bromide staining method, which showed viable cells in the MT on days 5, 7, and 10 of cultivation. Histochemical and histological analyses were performed, including hematoxylin/eosin staining, which showed a good structure of the spheroids. Alcian blue staining revealed the presence of acid proteoglycans. Immunohistochemical analysis with ki-67 showed different patterns of cell proliferation. The MT were also subjected to pharmacological tests using the BeV, in the presence or absence of its AV. The results showed that the venom was not cytotoxic, but it caused morphological changes. The MT showed cell detachment, losing their structure. The antivenom was able to partially prevent the venom activities.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: