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Distribution of methyl and isopropyl N-methylanthranilates and their metabolites in organs of rats treated with these two essential-oil constituents

Miltojević, Ana B., Stojanović, Nikola M., Randjelović, Pavle J., Radulović, Niko S.
Food and chemical toxicology 2019 v.128 pp. 68-80
Choisya ternata, alkaloids, animal tissues, antidepressants, biotransformation, brain, essential oils, gas chromatography-mass spectrometry, heart, hydrolysis, kidneys, liver, lungs, metabolites, moieties, multivariate analysis, muscles, nephroprotective effect, rats, sleep, spleen, toxicology, tranquilizers
Two volatile alkaloids, methyl (MMA) and isopropyl N-methylanthranilates (IMA), identified in the essential oil of Choisya ternata Kunth (Rutaceae), have been proven to possess polypharmacological properties (antinociceptive, anti-inflammatory, gastro-, hepato-, nephroprotective activities, anxiolytic and antidepressant properties, and likewise an effect on diazepam-induced sleep). In the continuation of our investigation of their urinary-metabolite profiles, we performed GC-MS analyses of the diethyl-ether extracts of selected tissues (liver, kidneys, heart, brain, lungs, quadriceps femoris muscle, and spleen) of rats intraperitoneally treated with MMA or IMA (2 g kg−1). Organ-metabolite profiles of MMA and IMA were qualitatively mutually analogous (varying only in the alcohol moiety of the metabolites), and generally analogous to their urinary-metabolite profiles. The greatest diversity and the highest overall amount of anthranilate metabolites was found in the hepatic tissue. The principal anthranilate-related compounds in the organs of rats treated with MMA, among 12 detected, were the products of ester hydrolysis, N-methylanthranilic and anthranilic acids. In the tissues of IMA-treated rats, among 16 compounds, the most abundant ones were the unmetabolized IMA and N-methylanthranilic acid. A collection of the compositional data regarding the anthranilate-related metabolites was statistically treated by multivariate statistical analysis that provided a better insight into the possible biotransformation pathways.