Epoxyscillirosidine induced cytotoxicity and ultrastructural changes in a rat embryonic cardiomyocyte (H9c2) cell line

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dc.contributor.author Isa, Hamza Ibrahim
dc.contributor.author Ferreira, Gezina Catharina Helena
dc.contributor.author Crafford, Jan Ernst
dc.contributor.author Botha, C.J. (Christoffel Jacobus)
dc.date.accessioned 2019-08-22T09:03:05Z
dc.date.available 2019-08-22T09:03:05Z
dc.date.issued 2019-05
dc.description.abstract Moraea pallida Bak. (yellow tulp) poisoning is the most important cardiac glycoside-induced intoxication in ruminants in South Africa. The toxic principle, 1α, 2α-epoxyscillirosidine, is a bufadienolide. To replace the use of sentient animals in toxicity testing, the aim of this study was to evaluate the cytotoxic effects of epoxyscillirosidine on rat embryonic cardiomyocytes (H9c2 cell line). This in vitro cell model can then be used in future toxin neutralization or toxico-therapy studies. Cell viability, evaluated with the methyl blue thiazol tetrazolium (MTT) assay, indicated a hormetic dose/concentration response, characterized by a biphasic low dose stimulation and high dose inhibition. Increased cell membrane permeability and leakage, as expected with necrotic cells, were demonstrated with the lactate dehydrogenase (LDH) assay. The LC50 was 382.68, 132.28 and 289.23 μM for 24, 48, and 72 h respectively. Numerous cytoplasmic vacuoles, karyolysis and damage to the cell membrane, indicative of necrosis, were observed at higher doses. Ultra-structural changes suggested that the cause of H9c2 cell death, subsequent to epoxyscillirosidine exposure, is necrosis, which is consistent with myocardial necrosis observed at necropsy. Based on the toxicity observed, and supported by ultra-structural findings, the H9c2 cell line could be a suitable in vitro model to evaluate epoxyscillirosidine neutralization or other therapeutic interventions in the future. View Full-Text en_ZA
dc.description.department Paraclinical Sciences en_ZA
dc.description.department Veterinary Tropical Diseases en_ZA
dc.description.librarian hj2019 en_ZA
dc.description.sponsorship The Tshwane Animal Health Innovation Cluster (Grant number TAHC 12-00031). en_ZA
dc.description.uri http://www.mdpi.com/journal/toxins en_ZA
dc.identifier.citation Isa, H.I., Ferreira, G.C.H., Crafford, J.E. et al. Epoxyscillirosidine induced cytotoxicity and ultrastructural changes in a rat embryonic cardiomyocyte (H9c2) cell line. Toxins 2019, 11(5), 284; https://doi.org/10.3390/toxins11050284. en_ZA
dc.identifier.issn 2072-6651 (online)
dc.identifier.other 10.3390/toxins11050284
dc.identifier.uri http://hdl.handle.net/2263/71170
dc.language.iso en en_ZA
dc.publisher MDPI en_ZA
dc.rights © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). en_ZA
dc.subject Cardiac glycoside en_ZA
dc.subject Epoxyscillirosidine en_ZA
dc.subject H9c2 cells en_ZA
dc.subject Hormesis en_ZA
dc.subject LDH assay en_ZA
dc.subject Lactate dehydrogenase (LDH) en_ZA
dc.subject Moraea pallida en_ZA
dc.subject MTT assay en_ZA
dc.subject Methyl blue thiazol tetrazolium (MTT) en_ZA
dc.subject Necrosis en_ZA
dc.subject Poisoning en_ZA
dc.title Epoxyscillirosidine induced cytotoxicity and ultrastructural changes in a rat embryonic cardiomyocyte (H9c2) cell line en_ZA
dc.type Article en_ZA


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