monensin and Mycoses

1. Monensin A, an important antibiotic ionophore that is primarily employed to treat coccidiosis, selectively complexes and transports sodium cations across lipid membranes and displays a variety of biological properties. 2. In this study, we evaluated the fungi Cunninghamella echinulata var. elegans ATCC 8688A, Cunninghamella elegans NRRL 1393 ATCC 10028B and human hepatic microsomes as CYP-P450 models to investigate the in vitro metabolism of monensin A and compare the products with the metabolites produced in vivo. 3. Mass spectrometry analysis of the products from these model systems revealed the formation of three metabolites: 3-O-demethyl monensin A, 12-hydroxy monensin A and 12-hydroxy-3-O-demethyl monensin A. We identified these products by tandem mass spectrometry and through comparison with the in vivo metabolites. 4. This analysis demonstrated that the model systems produce the same metabolites found in in vivo studies, thus they could be used to predict the metabolism of monensin A. Furthermore, we verified that liquid chromatography coupled to mass spectrometry is a powerful tool to study the in vitro metabolism of drugs, because it allows the successful identifications of several derivatives from different metabolic models.

Topics: Chromatography, Liquid; Cunninghamella; Humans; Ionophores; Liver; Mass Spectrometry; Microsomes, Liver; Monensin; Mycoses; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

Previous research at this station adapted a maximal dose response (MDR) method of evaluating vitamin A status and utilization for use in beef cattle. This method was used in two experiments. In this first experiment, forty-eight crossbred steers (average weight, 284 kg) were fed diets supplemented with salt, monensin or both, and injected with vitamin E, zinc or selenium. Steers receiving monensin had higher (38.5 micrograms/dl, monensin; 31.0 micrograms/dl, controls) initial plasma concentrations of vitamin A (P = .14). However, monensin did not affect post-dosing (MDR) vitamin A concentrations. None of the other dietary treatments or injections affected either pre- or post-dosing concentrations of vitamin A in the plasma. In a second experiment 23 lactating multiparous beef cows (average weight, 500 kg) grazing either fungal endophyte-infected or endophyte-free tall fescue were used to assess possible influences of infected fescue upon vitamin A metabolism. Fungal endophyte infection did not affect either pre- (44.9 micrograms/dl, end-noninf.; 47.7 micrograms/dl, end-inf.) or post-dosing (57.2 micrograms/dl, end-noninf.; 59.3 micrograms/dl, end-inf.) vitamin A concentrations.

Topics: Acremonium; Animals; Cattle; Diet; Female; Male; Monensin; Mycoses; Poaceae; Selenium; Sodium Chloride; Vitamin A; Vitamin E; Zinc