Abstract
The etiology of vitamin B6 depletion in inflammation remains unknown. Hepatic vitamin B6 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 B6 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 B6 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 B6 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 B6 across cell membrane, elevated circulating PL may facilitate the cellular uptake and utilization of B6. The elevated plasma PLP may increase vitamin B6 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 B6 status.
Footnotes
This project was supported in part by the National Science Council [Grant NSC98-2320-B005-004MY3] (to E.-P.I.C.); and the Department of Health in Taiwan [Grant DOH 97-TD-D-113-97011] (to E.-P.I.C.).
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.174839.
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ABBREVIATIONS:
- RA
- rheumatoid arthritis
- PL
- pyridoxal
- PLP
- pyridoxal 5′-phosphate
- PA
- pyridoxic acid
- DMARD
- disease-modifying antirheumatic drug
- PDXK
- pyridoxine kinase
- PMP
- pyridoxamine-5′-phosphate
- PMPO
- pyridoxamine-5′-phosphate oxidase
- PM
- pyridoxamine
- PDXP
- pyridoxal-5′-phosphate phosphatase
- HPLC
- high-performance liquid chromatography.
- Received September 7, 2010.
- Accepted December 27, 2010.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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