Long-Term Prednisolone Treatments Increase Bioactive Vitamin B₆Synthesis In Vivo

Abstract

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 5Ј-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-5Ј-phosphate oxidase (PMPO) and suppressed PLP catabolic enzyme pyridoxal-5Ј-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.

Vitamin B-6 deficiency is common and associated with poor long-term outcome in renal transplant recipients,

“…Interestingly, Lacour et al (4) previously suggested that the deficit in plasma PLP in RTRs could originate from the period on dialysis and that it might be maintained by the immunosuppressive medication used by RTRs; however, they acknowledge that data for such a drug-induced effect were lacking (5). To our knowledge, the potential in vivo effects of prednisolone on vitamin B-6 isoforms have been investigated in one intervention study in experimental animals (28). It was found that long-term prednisolone treatment increased circulating plasma concentrations of PLP, pyridoxal, and pyridoxic acid in rats and mice.…”

A novel role of the tumor suppressor GNMT in cellular defense against DNA damage

“…Before the dietary intervention, mice were fed the AIN‐93M diet (2 mg folic acid/kg, Dyets, Bethlehem, PA) for 2 weeks for adaptation and then were fed either the folate‐supplemented diet (20 mg folic acid/kg), or the folate‐deficient diet (0 mg folic acid/kg) that were based on the AIN‐93M formula except for the folate content. Vitamin‐free casein was used in both diets . Mice were fed the designated diets for an additional 8 weeks.…”

“…Vitamin-free casein was used in both diets. 29 Mice were fed the designated diets for an additional 8 weeks. Mice fed the chow diet (2 mg folic acid/kg) ad libitum throughout the study were used as a reference group for adequate folate status.…”

Clinical use of cyclooxygenase inhibitors impairs vitamin B-6 metabolism

“…Briefly, perchloric acid-extracted tissue supernatant fluid was incubated (30 min in the dark) with derivatization solution (250 mg semicarbazide and glycine/mL). Samples were filtered through 0.45-mm microspin filters before HPLC analysis (28). The HPLC system consisted of a Hitachi L-2130 intelligent pump connected to an L-2480 fluorescence detector and L-2100 autosampler (Hitachi).…”

“…Study 2 investigated the effects of longterm physiologic doses of celecoxib and naproxen treatments on vitamin B-6 metabolism in hypercholesterolemic animals. In study 1, 18 male, 4-wk-old C57BL/6J mice (National Laboratory Animal Center) were fed a standard AIN-93M diet (Dyets) that contained 6 mg pyridoxine/kg diet throughout the study period (28). In study 2, 18 male, 7-wk-old Syrian hamsters (National Laboratory Animal Centern) were fed a modified AIN-93M hypercholesterolemic diet (10% corn oil plus 0.2% cholesterol) that contained 6 mg pyridoxine/kg diet throughout the study period (Dyets).…”