Profiles in altered metabolism. IV—induction of acute dicarboxylic aciduria following 2-octynoic acid administration to the rat

Montgomery, J. A.; Mamer, Orval; Colle, Eleanor

doi:10.1002/bms.1200180610

Cited by 2 publications

(1 citation statement)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although several of the labrafil/CO- and PEG 300-induced urinary perturbations were characteristic of other xenobiotic induced urinary effects ( , ), the suite of urinary perturbations observed with both vehicles was unique, reflected by their distinct mapping positions. PEG is a substance of known low toxic potential with an LD 50 in the mouse and rat for PEG 400 by p.o.…”

Section: Resultsmentioning

confidence: 99%

NMR-Based Metabonomic Studies on the Biochemical Effects of Commonly Used Drug Carrier Vehicles in the Rat

Beckwith-Hall¹,

Holmes²,

Lindon³

et al. 2002

Chem. Res. Toxicol.

View full text Add to dashboard Cite

The biochemical effects of a series of commonly used drug carrier vehicles were investigated using (1)H NMR spectroscopic and pattern recognition based metabonomic analysis. Animals were treated by oral gavage with six dosage vehicles: 0.5% (w/v) sodium carboxymethylcellulose/0.2% (v/v)tween; microemulsion (consisting of propylene glycol, ethanol, cremophor, and corn oil glycerides); labrafil [consisting of poly(ethylene glycol) 300 esterified with oleic acid] (30%)/corn oil (70%); 0.1 M sodium phosphate buffered water; poly(ethylene glycol) 300 and 0.5% methocel. Urine samples (n = 7) collected over a 96 h period post administration were analyzed using 600 MHz (1)H NMR spectroscopy, and principal components analysis of the spectral data was used to analyze these data. Of the six vehicles studied, three (labrafil/corn oil, PEG 300 and microemulsion) gave rise to strong vehicle-related signals in the (1)H NMR spectra of urine and were, therefore, deemed to be less suitable for NMR-based toxicity studies. To investigate any biochemical consequences of vehicle dosing, PCA was used to analyze spectral regions that did not contain vehicle-related signals, i.e., the NMR-detectable endogenous metabolite profile. PEG 300 and labrafil/corn oil induced changes in the biochemical composition of urine including increased concentrations of dicarboxylic acids, creatinine, taurine, and sugars, indicating that these vehicles were bioactive in their own right and that this might confound interpretation of biochemical effects of weakly toxic drugs dosed in these carriers. This study shows the importance of selecting appropriate vehicles for NMR-based metabonomic studies with a view to minimizing the possibility of vehicle resonances obscuring endogenous compound peaks. Furthermore, we have shown that at least two of the commonly used drug carrier vehicles caused metabolic perturbations in the urine profile. These alterations in the biochemical profile reflect vehicle-induced changes in the physiological status of the organism that may obscure the pharmacologic or toxicologic effects of drugs.

show abstract

Section: Resultsmentioning

confidence: 99%