Bioaccumulation and Distribution of Indospicine and Its Foregut Metabolites in Camels Fed Indigofera spicata.

In vitro experiments have demonstrated that camel foregut-fluid has the capacity to metabolize indospicine, a natural toxin which causes hepatotoxicosis, but such metabolism is in competition with absorption and outflow of indospicine from the different segments of the digestive system. Six young camels were fed Indigofera spicata (337 µg indospicine/kg BW/day) for 32 days, at which time three camels were euthanized. The remaining camels were monitored for a further 100 days after cessation of this indospicine diet. In a retrospective investigation, relative levels of indospicine foregut-metabolism products were examined by UHPLC-MS/MS in plasma, collected during both accumulation and depletion stages of this experiment. The metabolite 2-aminopimelamic acid could be detected at low levels in almost all plasma samples, whereas 2-aminopimelic acid could not be detected. In the euthanized camels, 2-aminopimelamic acid could be found in all tissues except muscle, whereas 2-aminopimelic acid was only found in the kidney, pancreas, and liver tissues. The clearance rate for these metabolites was considerably greater than for indospicine, which was still present in plasma of the remaining camels 100 days after cessation of Indigofera consumption.

Pre-column fluorescence derivatization using leucine-coumarnylamide for HPLC determination of mono- and dicarboxylic acids in plasma.

A sensitive HPLC assay utilising a simple fluorescence pre-column labelling technique was developed for plasma level monitoring of different types of mono- and dicarboxylic acids. Carboxylic acids form mixed anhydrides with ethyl chloroformate in the presence of triethylamine; the mixed anhydrides further react with L-leucine-4-methyl-7-coumarinylamide, forming highly fluorescent and stable amides. Drugs with no chromophore (azelaic acid, and its longer carbon chain analogues) or week UV absorption (artelinic acid, enalaprilat) were used as model compounds. The plasma samples were extracted using ion exchange solid phase cartridges. The separation was performed on an Axxiom C18 (5 microns, 4.6 x 250 mm) column. The detector wavelengths were set at 330 nm for excitation and 390 nm for emission.

Preliminary studies of a dicarboxylic acid as an energy substrate in man.

Azelaic acid (Az), a straight saturated chain nine carbon dicarboxylic acid, was administered in saline form to six healthy male volunteers by iv route. Serum levels of Az and urinary amounts of both azelaic and pimelic (C7) acids were measured by an improved gas liquid chromatographic method. Stoichiometric analysis of Az metabolism was compared with that of glucose and palmitic acid. The respiratory quotient (RQ) as well as the ATP/CO2 ratio of Az were quite similar to that of palmitic acid. Therefore, Az oxidation is associated with a low cost of ATP synthesis in terms of carbon dioxide production. At the infusion rate used (7.5 g/hr) more than 50% of the administered dose was excreted in the urine. However, the remaining portion was cleared from the plasma in 200 min suggesting an uptake by body tissues which was also confirmed by indirect calorimetric analysis.