Next Article in Journal
The Efficiency of Microstrainers Filtration in the Process of Removing Phytoplankton with Special Consideration of Cyanobacteria
Next Article in Special Issue
Xanthium strumarium Fruit Extract Inhibits ATG4B and Diminishes the Proliferation and Metastatic Characteristics of Colorectal Cancer Cells
Previous Article in Journal
Safety and Efficacy of Intracavernosal Injections of AbobotulinumtoxinA (Dysport®) as Add on Therapy to Phosphosdiesterase Type 5 Inhibitors or Prostaglandin E1 for Erectile Dysfunction—Case Studies
Previous Article in Special Issue
Whole-Cell Multiparameter Assay for Ricin and Abrin Activity-Based Digital Holographic Microscopy
Open AccessArticle

Epoxyscillirosidine Induced Cytotoxicity and Ultrastructural Changes in a Rat Embryonic Cardiomyocyte (H9c2) Cell Line

1
Department of Paraclinical Sciences, University of Pretoria, Onderstepoort 0110, Gauteng, South Africa
2
Department of Veterinary Pharmacology and Toxicology, Ahmadu Bello University, Zaria 810107, Nigeria
3
Department of Veterinary Tropical Diseases, University of Pretoria, Onderstepoort 0110, Gauteng, South Africa
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(5), 284; https://doi.org/10.3390/toxins11050284
Received: 18 April 2019 / Revised: 30 April 2019 / Accepted: 5 May 2019 / Published: 21 May 2019
(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)
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
Keywords: Cardiac glycoside; epoxyscillirosidine; H9c2 cells; hormesis; LDH assay; Moraea pallida; MTT assay; necrosis; poisoning Cardiac glycoside; epoxyscillirosidine; H9c2 cells; hormesis; LDH assay; Moraea pallida; MTT assay; necrosis; poisoning
Show Figures

Figure 1

MDPI and ACS Style

Isa, H.I.; Ferreira, G.C.H.; Crafford, J.E.; Botha, C.J. Epoxyscillirosidine Induced Cytotoxicity and Ultrastructural Changes in a Rat Embryonic Cardiomyocyte (H9c2) Cell Line. Toxins 2019, 11, 284.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop