Himmelfarb Jonathan, Kane Jane, McMonagle Ellen, Zaltas Eric, Bobzin Steve, Boddupalli Sekhar, Phinney Stephen, Miller Guy
Maine Medical Center, Portland, Maine 04102, USA.
Kidney Int. 2003 Sep;64(3):978-91. doi: 10.1046/j.1523-1755.2003.00151.x.
The metabolism of alpha and gamma tocopherol, the major components of vitamin E, have not been studied in uremic patients. The major pathway of tocopherol metabolism is via phytyl side chain oxidation, leaving carboxyethyl-hydroxychromans (CEHC) as metabolites. Alpha and gamma CEHC are water soluble, renally excreted, with known potent anti-inflammatory and antioxidative properties.
We examined serum alpha and gamma tocopherol and respective CEHC concentrations in 15 healthy subjects and 15 chronic hemodialysis patients.
Serum alpha tocopherol levels were similar in hemodialysis patients (12.03 +/- 1.34 microg/mL) and healthy subjects (11.21 +/- 0.20 microg/mL), while serum gamma tocopherol levels were significantly greater in hemodialysis patients (3.17 +/- 0.37 microg/mL) compared to healthy subjects (1.08 +/- 0.06 microg/mL, P < 0.0001). Serum alpha and gamma CEHC levels were tenfold and sixfold higher in hemodialysis patients compared to healthy subjects, respectively (both P < 0.0001). Serum alpha and gamma tocopherol levels and CEHC metabolites were also measured after supplementation of alpha- or gamma-enriched mixed tocopherols in both hemodialysis patients and healthy subjects. Tocopherol administration resulted in modest or nonsignificant changes in serum tocopherol concentrations, while markedly increasing serum CEHC concentrations in both healthy subjects and hemodialysis patients. Hemodialysis resulted in no change in the serum alpha or gamma tocopherol concentrations while decreasing serum alpha CEHC and gamma CEHC levels by 63% and 53%, respectively (both P = 0.001 versus predialysis). Fourteen-day administration of gamma-enriched but not alpha tocopherols lowered median C-reactive protein (CRP) significantly in hemodialysis patients (4.4 to 2.1 mg/L, P < 0.02).
First, serum alpha and gamma CEHC accumulate in uremic patients compared to healthy subjects; second, supplementation with tocopherols dramatically increases serum CEHC levels in both healthy subjects and hemodialysis patients; and, finally, CEHC accumulation may mediate anti-inflammatory and antioxidative effects of tocopherols in hemodialysis patients.
维生素E的主要成分α-生育酚和γ-生育酚在尿毒症患者中的代谢情况尚未得到研究。生育酚代谢的主要途径是通过植基侧链氧化，生成羧乙基-羟基色满（CEHC）作为代谢产物。α-CEHC和γ-CEHC是水溶性的，经肾脏排泄，具有已知的强效抗炎和抗氧化特性。
我们检测了15名健康受试者和15名慢性血液透析患者血清中的α-生育酚和γ-生育酚以及各自的CEHC浓度。
血液透析患者的血清α-生育酚水平（12.03±1.34微克/毫升）与健康受试者（11.21±0.20微克/毫升）相似，而血液透析患者的血清γ-生育酚水平（3.17±0.37微克/毫升）显著高于健康受试者（1.08±0.06微克/毫升，P<0.0001）。血液透析患者的血清α-CEHC和γ-CEHC水平分别比健康受试者高10倍和6倍（均P<0.0001）。在血液透析患者和健康受试者中补充富含α-或γ-的混合生育酚后，还检测了血清α-生育酚和γ-生育酚水平以及CEHC代谢产物。给予生育酚后，血清生育酚浓度有适度变化或无显著变化，而在健康受试者和血液透析患者中血清CEHC浓度均显著升高。血液透析对血清α-生育酚或γ-生育酚浓度无影响，但血清α-CEHC和γ-CEHC水平分别降低了63%和53%（与透析前相比，均P=0.001）。在血液透析患者中，给予富含γ-的生育酚而非α-生育酚14天可显著降低C反应蛋白（CRP）中位数（从4.4降至2.1毫克/升，P<0.02）。
第一，与健康受试者相比，尿毒症患者血清中的α-CEHC和γ-CEHC会蓄积；第二，补充生育酚可使健康受试者和血液透析患者的血清CEHC水平显著升高；最后，CEHC的蓄积可能介导了生育酚在血液透析患者中的抗炎和抗氧化作用。
