ABSTRACT
Geigeria poisoning, referred to as 'vermeersiekte' is an important plant poisoning in southern Africa. Three sesquiterpene lactones, isogeigerin acetate (1) ivalin (2) and geigerin (3) were isolated and purified from Geigeria aspera Harv. (Asteraceae). Structures were deduced using 1 and 2D NMR spectroscopy and mass spectrometry, while the absolute configurations of compounds 1 and 3 were determined for the first time by X-ray crystal diffraction analyses. Cytotoxicity of isogeigerin acetate, ivalin and geigerin were compared by exposing a murine skeletal myoblast (C2C12) cell line to varying concentrations of the three sesquiterpene lactones isolated. Cell viability was assessed using the methyl-thiazolyl-tetrazolium (MTT) assay. The EC50s were 3.746, 0.0029 and 3.792 mM for isogeigerin acetate (1), ivalin (2) and geigerin (3), respectively. The results indicate that ivalin is much more toxic, approximately 1000 times, in vitro compared to isogeigerin acetate and geigerin.
Subject(s)
Geigeria/chemistry , Lactones/isolation & purification , Lactones/pharmacology , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Animals , Carbon-13 Magnetic Resonance Spectroscopy , Cell Death/drug effects , Cell Line , Cell Line, Tumor , Lactones/chemistry , Mice , Proton Magnetic Resonance Spectroscopy , Sesquiterpenes/chemistryABSTRACT
Diplodiosis is an important neuromycotoxicosis of ruminants in South Africa when grazing on harvested maize fields in winter. It is believed to be caused by mycotoxin(s) synthesised by Stenocarpella (Diplodia) maydis. Although several metabolites have been isolated from S. maydis culture material, none of these have been administered to ruminants to reproduce the disease. The objectives of this study were to isolate diplodiatoxin and to administer it to juvenile goats. Diplodiatoxin, considered as a major metabolite, was purified from S. maydis-infected maize cultures (Coligny 2007 isolate). Following intravenous administration of 2 mg and 4 mg diplodiatoxin/kg body weight for five consecutive days to two juvenile goats, no clinical signs reminiscent of diplodiosis were observed. Based on previous experimental results and if diplodiatoxin was the causative compound, the dosage regimen employed was seemingly appropriate to induce diplodiosis. In addition, intraruminal administration of 2 mg/kg diplodiatoxin to one goat for three consecutive days also did not induce clinical signs. It appears as if diplodiatoxin alone is not the causative compound. Other metabolites and/or mixtures of diplodiatoxin and other mycotoxins, when available in sufficient quantities, should also be evaluated.
