Quantification of xenobiotic effects on endogenous retinoic acid by LC-MS/MS

ANYL 318

Maureen A. Kane, makane@berkeley.edu and Joseph L. Napoli. Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 150 Morgan Hall, MC #3104, Berkeley, CA 94720-3104
Vitamin A and its derivatives support a wide range of biological actions essential for development, differentiation, vision, reproduction, and immune response. Retinoic acid (RA), the major active metabolite of vitamin A, is responsible for a multitude of systemic and specific effects, including a function in the nervous system of developing and mature vertebrates. Quantification of endogenous retinoic acids in specific loci would contribute to understanding retinoid function; however, low endogenous concentrations and small tissue sizes of specific loci previously hampered quantification of RA in individual animals/embryos. Changes in endogenous levels of retinoids have been linked to various xenobiotics, and may reflect disease states and metabolic disorders. Drawing on LC-MS/MS methodology, we have developed a sensitive, specific assay for RA and/or its isomers. Here, we present data on improvements to our existing RA assay and examine the effect of xenobiotics on RA levels in adult and embryonic mouse brain. Altered RA levels may contribute to aberrant brain development, cognitive dysfunction, and depression. Although xenobiotic effects on other vitamin A derivatives (retinol and retinyl ester) have been studied to a limited extent, little information is available on their impact on RA, the retinol metabolite with direct biological activity.