Cytotoxicity of the Sesquiterpene Lactones, Ivalin and Parthenolide in Murine Muscle Cell Lines and Their Effect on Desmin, a Cytoskeletal Intermediate Filament

Vermeersiekte or “vomiting disease” is an economically important disease of ruminants following ingestion of <i>Geigeria</i> (<i>G.</i>) species in South Africa. Sheep are more susceptible, and poisoning is characterized by stiffness, regurgitation, bloat, paresis, and paraly...

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Main Authors: Christo J. Botha, Y. Zethu Mathe, Gezina C. H. Ferreira, E. Annette Venter
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/12/7/459
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author Christo J. Botha
Y. Zethu Mathe
Gezina C. H. Ferreira
E. Annette Venter
author_facet Christo J. Botha
Y. Zethu Mathe
Gezina C. H. Ferreira
E. Annette Venter
author_sort Christo J. Botha
collection DOAJ
description Vermeersiekte or “vomiting disease” is an economically important disease of ruminants following ingestion of <i>Geigeria</i> (<i>G.</i>) species in South Africa. Sheep are more susceptible, and poisoning is characterized by stiffness, regurgitation, bloat, paresis, and paralysis. Various sesquiterpene lactones have been implicated as the cause of poisoning. The in vitro cytotoxicity of two sesquiterpene lactones, namely, ivalin (purified from <i>Geigeria aspera</i>) and parthenolide (a commercially available sesquiterpene lactone), were compared using mouse skeletal myoblast (C2C12) and rat embryonic cardiac myocyte (H9c2) cell lines, representing the oesophageal, skeletal and cardiac muscles, which are affected in sheep. For 24, 48, and 72 h, both cell lines were exposed. A colorimetric viability assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), was used to assess cytotoxicity. A concentration-dependent cytotoxic response was observed in both cell lines, however, the C2C12 cells were more sensitive, with the half-maximal effective concentrations (EC<sub>50</sub>s) ranging between 2.7 and 3.3 µM. In addition, the effect that ivalin and parthenolide has on desmin, an important cytoskeletal intermediate filament in myocytes, was evaluated using the C2C12 myoblasts. Disorganization and aggregation of desmin were caused by both sesquiterpene lactones, which could clarify some of the ultrastructural lesions described in vermeersiekte.
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spelling doaj.art-e99bb4e10b5c4e44a7f93bd81bfb09252023-11-20T07:10:56ZengMDPI AGToxins2072-66512020-07-0112745910.3390/toxins12070459Cytotoxicity of the Sesquiterpene Lactones, Ivalin and Parthenolide in Murine Muscle Cell Lines and Their Effect on Desmin, a Cytoskeletal Intermediate FilamentChristo J. Botha0Y. Zethu Mathe1Gezina C. H. Ferreira2E. Annette Venter3Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X 04, Onderstepoort 0110, South AfricaDepartment of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X 04, Onderstepoort 0110, South AfricaDepartment of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X 04, Onderstepoort 0110, South AfricaDepartment of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X 04, Onderstepoort 0110, South AfricaVermeersiekte or “vomiting disease” is an economically important disease of ruminants following ingestion of <i>Geigeria</i> (<i>G.</i>) species in South Africa. Sheep are more susceptible, and poisoning is characterized by stiffness, regurgitation, bloat, paresis, and paralysis. Various sesquiterpene lactones have been implicated as the cause of poisoning. The in vitro cytotoxicity of two sesquiterpene lactones, namely, ivalin (purified from <i>Geigeria aspera</i>) and parthenolide (a commercially available sesquiterpene lactone), were compared using mouse skeletal myoblast (C2C12) and rat embryonic cardiac myocyte (H9c2) cell lines, representing the oesophageal, skeletal and cardiac muscles, which are affected in sheep. For 24, 48, and 72 h, both cell lines were exposed. A colorimetric viability assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), was used to assess cytotoxicity. A concentration-dependent cytotoxic response was observed in both cell lines, however, the C2C12 cells were more sensitive, with the half-maximal effective concentrations (EC<sub>50</sub>s) ranging between 2.7 and 3.3 µM. In addition, the effect that ivalin and parthenolide has on desmin, an important cytoskeletal intermediate filament in myocytes, was evaluated using the C2C12 myoblasts. Disorganization and aggregation of desmin were caused by both sesquiterpene lactones, which could clarify some of the ultrastructural lesions described in vermeersiekte.https://www.mdpi.com/2072-6651/12/7/459C2C12 (mouse skeletal myoblasts)cytoskeletoncytotoxicitydesmin<i>Geigeria</i>H9c2 (rat embryonic cardiac myocytes)
spellingShingle Christo J. Botha
Y. Zethu Mathe
Gezina C. H. Ferreira
E. Annette Venter
Cytotoxicity of the Sesquiterpene Lactones, Ivalin and Parthenolide in Murine Muscle Cell Lines and Their Effect on Desmin, a Cytoskeletal Intermediate Filament
Toxins
C2C12 (mouse skeletal myoblasts)
cytoskeleton
cytotoxicity
desmin
<i>Geigeria</i>
H9c2 (rat embryonic cardiac myocytes)
title Cytotoxicity of the Sesquiterpene Lactones, Ivalin and Parthenolide in Murine Muscle Cell Lines and Their Effect on Desmin, a Cytoskeletal Intermediate Filament
title_full Cytotoxicity of the Sesquiterpene Lactones, Ivalin and Parthenolide in Murine Muscle Cell Lines and Their Effect on Desmin, a Cytoskeletal Intermediate Filament
title_fullStr Cytotoxicity of the Sesquiterpene Lactones, Ivalin and Parthenolide in Murine Muscle Cell Lines and Their Effect on Desmin, a Cytoskeletal Intermediate Filament
title_full_unstemmed Cytotoxicity of the Sesquiterpene Lactones, Ivalin and Parthenolide in Murine Muscle Cell Lines and Their Effect on Desmin, a Cytoskeletal Intermediate Filament
title_short Cytotoxicity of the Sesquiterpene Lactones, Ivalin and Parthenolide in Murine Muscle Cell Lines and Their Effect on Desmin, a Cytoskeletal Intermediate Filament
title_sort cytotoxicity of the sesquiterpene lactones ivalin and parthenolide in murine muscle cell lines and their effect on desmin a cytoskeletal intermediate filament
topic C2C12 (mouse skeletal myoblasts)
cytoskeleton
cytotoxicity
desmin
<i>Geigeria</i>
H9c2 (rat embryonic cardiac myocytes)
url https://www.mdpi.com/2072-6651/12/7/459
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