Glutathione redox potential is low and glutathionylated and cysteinylated hemoglobin levels are elevated in maintenance hemodialysis patients

被引:43
作者
Khazim, Khaled
Giustarini, Daniela
Rossi, Ranieri
Verkaik, Darlene
Cornell, John E.
Cunningham, Sue E. D.
Mohammad, Maryam
Trochta, Kara
Lorenzo, Carlos
Folli, Franco
Bansal, Shweta
Fanti, Paolo
机构
[1] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA
[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, Sch Med, San Antonio, TX 78229 USA
[3] Univ Texas Hlth Sci Ctr San Antonio, Sch Hlth Profess, Program Dietet & Nutr, San Antonio, TX 78229 USA
[4] Audie L Murphy Vet Mem Hosp, San Antonio, TX USA
[5] Western Galilee Hosp, Div Nephrol, Nahariyya, Israel
[6] Univ Siena, Lab Pharmacol & Toxicol, Dept Life Sci, I-53100 Siena, Italy
关键词
CHROMATOGRAPHY-MASS SPECTROMETRY; CHRONIC KIDNEY-DISEASE; OXIDATIVE STRESS; LIQUID-CHROMATOGRAPHY; RESPIRATORY BURST; CATION CHANNELS; S-THIOLATION; HUMAN PLASMA; BLOOD; ERYTHROCYTES;
D O I
10.1016/j.trsl.2012.12.014
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Glutathione (GSH), the most abundant intracellular low molecular mass thiol, protects cells from oxidative damage and regulates their function. Available information is inconsistent regarding levels of GSH and its disulfide (GSSG) in maintenance hemodialysis patients (HD). In addition, very limited data are available in HD about the relationship of GSH and GSSG with other measures of thiol metabolism and with the clinical profile. We tested the hypothesis that erythrocyte GSH/GSSG redox potential (Eh) is lower in HD than in healthy controls (C), and that Eh correlates with posttranslational thiolation of hemoglobin (Hb) and with standard clinical parameters in HD. In cross-sectional comparison of 33 stable HD and 21 C, we found a net loss of reducing capacity in HD as indicated by low erythrocyte GSH/GSSG Eh (-257 +/- 5.5 vs -270 +/- 5.6 mV, P = 0.002). Glutathionylated Hb (HbSSG) was 46% higher in HD than C (19.3 +/- 4.80 vs 13.2 +/- 2.79 pmol/mg Hb; P = 0.001) and cysteinylated Hb (HbSSCy) was >3-fold higher in HD than C (38.3 (29.0-63.3) vs 11.5 (9.6-17.2) pmol/mg Hb; P = 0.001). In multiple regression analysis of the HD cases, statistically significant associations were found between the GSH/GSSG Et, and the blood urea nitrogen (P = 0.001), creatinine (P = 0.015) and normalized protein catabolic rate (P = 0.05), after adjusting for age, race/ethnicity, and etiology of end-stage renal disease. In conclusion, accurate and precise analysis of GSH, GSSG, and mixed disulfides reveals loss of erythrocyte GSH/GSSG Eh, rise of both HbSSG and HbSSCy, and correlation of these thiols with measures of uremia and dietary protein intake.
引用
收藏
页码:16 / 25
页数:10
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