title: Effects of moniliformin in presence of cyclohexadepsipeptides on isolated mammalian tissue and cells.
abstract: Secondary metabolites produced by Fusarium spp. including beauvericin, enniatin and moniliformin are mycotoxins identified in cereal samples. The two cyclohexadepsipeptide mycotoxins beauvericin and enniatin have cytotoxic, antibiotic, insecticidal and ionophoric properties, while moniliformin primarily acts as a cardiotoxic mycotoxin. In this study, we examined the electromechanical and electrophysiological effects of moniliformin and moniliformin with ionophoric mycotoxins on cells (ventricular myocytes, Caco-2 cells) and in multicellular preparations (papillary muscles and terminal ilea of the guinea pig). Additionally, we investigated the influence of moniliformin on cell homeostasis in absence and presence of the cyclodepsipeptide mycotoxins (ventricular myocytes, Caco-2 cells). Experiments were performed using isometric measurements of contractility, intracellular microelectrode and patch-clamp techniques, and fluorescence imaging. While ionophoric cyclohexadepsipeptides affect action potential parameters and cell homeostasis, moniliformin did not change spontaneous rates of activity or cardiac action potentials. Furthermore, moniliformin had no effect on intracellular concentrations of ions and ATP, and did not affect pH. Moniliformin reduced contractility in papillary muscle, terminal ileum, the aorta and the pulmonary artery. However, moniliformin did not alter beauvericin and enniatin induced effects. From our studies, we conclude that moniliformin is not solely a cardiotoxic secondary metabolite, but also exerts its effects on smooth muscle. Moreover, there is no synergistic relationship between moniliformin and the concurrently produced cyclohexadepsipeptide mycotoxins beauvericin and enniatin.
authors.affiliation: Department of Pharmacology and Toxicology, University of Vienna, Pharmacy Centre, Althanstrasse 14, A-1090 Vienna, Austria.
authors.forename: M R
authors.initials: MR
authors.lastname: Kamyar
authors.forename: K
authors.initials: K
authors.lastname: Kouri
authors.forename: P
authors.initials: P
authors.lastname: Rawnduzi
authors.forename: C
authors.initials: C
authors.lastname: Studenik
authors.forename: R
authors.initials: R
authors.lastname: Lemmens-Gruber
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D018938:Caco-2 Cells; D002477:Cells / Q000187:drug effects; D003503:Cyclobutanes / Q000633:toxicity*; D047630:Depsipeptides / Q000633:toxicity*; D005670:Fusarium / Q000737:chemistry; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008839:Microelectrodes; D032342:Muscle Cells / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009183:Mycotoxins / Q000633:toxicity*; D010210:Papillary Muscles / Q000187:drug effects; D018408:Patch-Clamp Techniques
chemical_list: D000900:Anti-Bacterial Agents; D003503:Cyclobutanes; D047630:Depsipeptides; D009183:Mycotoxins; C100264:enniatins; C004456:beauvericin; C008539:moniliformin; D000255:Adenosine Triphosphate