24,25,28-Trihydroxyvitamin D2 and 24,25,26-trihydroxyvitamin D2: novel metabolites of vitamin D2

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Abstract
In our present study, we investigated the metabolic fate of 25-hydroxyvitamin D2 in the isolated perfused rate kidney and demonstrated its conversion not only into 24,25-dihydroxyvitamin D2 but also into two other new metabolites, namely, 24,25,28-trihydroxyvitamin D2 and 24,25,26-trihydroxyvitamin D2. The structure identification of the new metaboalites was established by the techniques of ultraviolet absorption spectrophotometry and mass spectrometry and by the characteristic nature of each new metabolite''s susceptibility to sodium metaperiodate oxidation. In order to demonstrate the physiological significance of the two new trihydroxy metabolites of vitamin D2, we induced hypervitaminosis D2 in a rat using [3.alpha.-3H]vitamin D2 and analyzed its plasma for the various [3.alpha.-3H]vitamin D2 metabolites on two different high-pressure liquid chromatography systems. The results indicate that both 24,35,28-trihydroxyvitamin D2 and 24,25,26-trihydroxyvitamin D2 circulate in the vitamin D2 intoxicated rat in significant amounts along with other previously identified monohydroxy and dihydroxy metabolites of vitamin D2, namely, 24-hydroxyvitamin D2, 25-hydroxyvitamin D2, and 24,25-dihydroxyvitamin D2. Thus, it may be hypothesized that the two new trihydroxy metabolites of vitamin D2 play an important physiological role in the deactivation of 25-hydroxyvitamin D2, especially during hypervitaminosis D2.