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標題: Long-Term Prednisolone Treatments Increase Bioactive Vitamin B(6) Synthesis In Vivo
作者: Chang, Hsin-Yueh
Jason, T.C.Tzen
Lin, Su-Jen
Wu, Yi-Ting
Chiang, En-Pei Isabel
關鍵字: coronary-artery-disease;performance liquid-chromatography;glutamic-pyruvic transaminase;rheumatoid-arthritis;glucocorticoid;treatment;pyridoxal 5'-phosphate;protein-binding;plasma;metabolism;risk
Project: Journal of Pharmacology and Experimental Therapeutics, Volume 337, Issue 1, Page(s) 102-109.
The etiology of vitamin B(6) depletion in inflammation remains unknown. Hepatic vitamin B(6) decreased in adrenalectomized rats, and such reductions were restored by an acute muscle injection of a very high dose of glucocorticoids. We tested the hypothesis that long-term prednisolone treatment for treating inflammation restores vitamin B(6) status by induction of tissue B6 metabolic enzymes. Two independent in vivo models were used. Lewis rats and C57BL/6J mice received prednisolone regimens that reflected clinical prednisolone uses in treating human inflammation. We found: 1) prednisolone increased circulating B6 vitamer pyridoxal 5'-phosphate (PLP; bioactive B6 vitamer), pyridoxal (PL), and 4-pyridoxic acid without altering vitamin B(6) excretion; 2) prednisolone simultaneously induced the hepatic PLP-synthesizing enzyme pyridoxine kinase (PDXK) and pyridoxamine-5'-phosphate oxidase (PMPO) and suppressed PLP catabolic enzyme pyridoxal-5'-phosphate phosphatase (PDXP); and 3) elevations in circulating PL were caused by its release from the liver, not by PLP dephosphorylation (PDXP was suppressed and alkaline phosphatase was unaltered). We conclude that long-term prednisolone treatments promoted hepatic bioactive vitamin B(6) synthesis by inducing the synthesizing enzymes PDXK and PMPO and simultaneously suppressing the catabolic enzyme PDXP. Prednisolone increased circulating B6 vitamer without altering urinary B6 excretion. As the major form of vitamin B(6) across cell membrane, elevated circulating PL may facilitate the cellular uptake and utilization of B6. The elevated plasma PLP may increase vitamin B(6) supply to tissues with a higher B6 demand during inflammation. Results from two independent in vivo models suggested a potential advantage of clinical prednisolone use in treating inflammation with respect to vitamin B(6) status.
ISSN: 0022-3565
DOI: 10.1124/jpet.110.174839
Appears in Collections:食品暨應用生物科技學系

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