Shawaqfeh, Mohammad S
(2014)
Potential Contributors To The Decreased Vitamin B6 Levels After Transplantation.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Vitamin B6 deficiency as measured by plasma concentrations of pyridoxal 5` phosphate (P5P), the active form of vitamin B6, has been reported in several organ transplant recipients. The highest incidence of vitamin B6 deficiency has been observed in small bowel transplant recipients. The current study evaluated the potential mechanisms (increased degradation of P5P due to higher levels of alkaline phosphatases; or decreased formation of P5P due to decreased expression and activity of pyridoxal kinase) that may contribute to such observations. Higher plasma concentrations of alkaline phosphatases, decreased plasma albumin concentrations and higher amount of excretion of 4-pyridoxic acid in the urine of small bowel transplant patients supported the role of increased degradation of P5P. Of the various medications used by transplant patients that were tested using computation approach, pantoprazole, trimethoprim, acyclovir, valganciclovir and mycophenolic acid appeared to be most likely to inhibit pyridoxal kinase. Tacrolimus, the primary immunosuppressive drug used in most transplant recipients had limited impact on pyridoxal kinase expression and activity. A pro-inflammatory cytokine, TNF-α, decreased the expression and activity of pyridoxal kinase in primary cultures of human hepatocytes. The higher plasma concentrations of TNF-α observed in small bowel transplant patients is consistent with a decreased activity of pyridoxal kinase in the liver of these patients, and supported decreased formation of P5P also as a contributor to the observed vitamin B6 deficiency. Additional studies in an animal model where an organ that was not directly involved in the absorption, formation or degradation of vitamin B6 (a composite allograft tissue transplantation), showed a significant reduction in the expression of pyridoxal kinase in the liver. This suggested that the process of organ transplantation (immune activation and inflammation) itself led to vitamin B6 deficiency. Our studies indicate that vitamin B6 deficiency is expected in all transplant recipients; however, the magnitude of deficiency is likely to be affected by the immunogenicity of the transplanted organ and the immune status of the patient. Given the potential effect of vitamin B6 deficiency (neurotoxicity), and the low cost of vitamin B6, it is prudent to consider supplementation of all transplant patients with vitamin B6.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Shawaqfeh, Mohammad S | mos16@pitt.edu | MOS16 | |
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| ETD Committee: |
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| Date: |
6 August 2014 |
| Date Type: |
Publication |
| Defense Date: |
21 July 2014 |
| Approval Date: |
6 August 2014 |
| Submission Date: |
5 August 2014 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Number of Pages: |
181 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Vitamin B6 , Transplantation |
| Date Deposited: |
06 Aug 2014 14:35 |
| Last Modified: |
06 Aug 2019 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/22628 |
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