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8-hydroxy-2'-deoxyguanosine of leukocyte DNA as a marker of oxidative stress in chronic hemodialysis patients.
Am J Kidney Dis 2000; 36(5):934-44AJ

Abstract

In contrast to proteins and lipids, oxidative damage to DNA has not been well studied in patients undergoing hemodialysis (HD). We hypothesized that phagocytes are activated after blood-membrane contact during HD, and oxidants from metabolic activation can damage leukocyte DNA. To test this hypothesis, the 8-hydroxy-2'-deoxyguanosine (8-OHdG) content of leukocyte DNA was measured by high-performance liquid chromatography electrochemical detection method in 35 age- and sex-matched healthy subjects, 22 undialyzed patients with advanced renal failure, and 109 HD patients to assess the relation between oxidative DNA damage and complement-activating membranes, blood antioxidants, and iron status. Dialysis membranes were classified into complement-activating (cellulose; n = 55) and non-complement-activating (polymethylmethacrylate [PMMA]; n = 35; polysulfone [PS]; n = 19) membranes. We found increased oxidative stress in undialyzed and HD patients based on a decrease in plasma levels of ascorbate and alpha-tocopherol adjusted for blood lipid (alpha-tocopherol/lipid), serum albumin, and reduced glutathione levels in whole blood and an increase in oxidized glutathione levels in whole blood compared with controls (P < 0.001). The greatest 8-OHdG level in leukocyte DNA was in HD patients, followed by undialyzed patients and healthy controls (P < 0.001), and was significantly greater in HD patients using cellulose membranes than those using PMMA or PS membranes (P < 0.001). 8-OHdG levels correlated with plasma alpha-tocopherol/lipid (r = -0.314; P < 0.005), serum iron (r = 0. 446; P < 0.001), and transferrin saturation values (r = 0.202; P < 0.05) in the analysis of all HD patients. In a 6-week crossover study, 8-OHdG levels significantly decreased after the switch from cellulose to synthetic membranes for 2 weeks and increased after the shift from synthetic to cellulose membranes (P < 0.05). Iron metabolism indices and plasma alpha-tocopherol/lipid values did not change significantly in the study period. We conclude that 8-OHdG content in leukocyte DNA is a biomarker of oxidant-induced DNA damage in HD patients. Oxidative DNA damage is a consequence of uremia, further augmented by complement-activating membranes.

Authors+Show Affiliations

Institute of Clinical Medicine and the Department of Biochemistry and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11054349

Citation

Tarng, D C., et al. "8-hydroxy-2'-deoxyguanosine of Leukocyte DNA as a Marker of Oxidative Stress in Chronic Hemodialysis Patients." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 36, no. 5, 2000, pp. 934-44.
Tarng DC, Huang TP, Wei YH, et al. 8-hydroxy-2'-deoxyguanosine of leukocyte DNA as a marker of oxidative stress in chronic hemodialysis patients. Am J Kidney Dis. 2000;36(5):934-44.
Tarng, D. C., Huang, T. P., Wei, Y. H., Liu, T. Y., Chen, H. W., Wen Chen, T., & Yang, W. C. (2000). 8-hydroxy-2'-deoxyguanosine of leukocyte DNA as a marker of oxidative stress in chronic hemodialysis patients. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 36(5), pp. 934-44.
Tarng DC, et al. 8-hydroxy-2'-deoxyguanosine of Leukocyte DNA as a Marker of Oxidative Stress in Chronic Hemodialysis Patients. Am J Kidney Dis. 2000;36(5):934-44. PubMed PMID: 11054349.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 8-hydroxy-2'-deoxyguanosine of leukocyte DNA as a marker of oxidative stress in chronic hemodialysis patients. AU - Tarng,D C, AU - Huang,T P, AU - Wei,Y H, AU - Liu,T Y, AU - Chen,H W, AU - Wen Chen,T, AU - Yang,W C, PY - 2000/10/31/pubmed PY - 2001/2/28/medline PY - 2000/10/31/entrez SP - 934 EP - 44 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am. J. Kidney Dis. VL - 36 IS - 5 N2 - In contrast to proteins and lipids, oxidative damage to DNA has not been well studied in patients undergoing hemodialysis (HD). We hypothesized that phagocytes are activated after blood-membrane contact during HD, and oxidants from metabolic activation can damage leukocyte DNA. To test this hypothesis, the 8-hydroxy-2'-deoxyguanosine (8-OHdG) content of leukocyte DNA was measured by high-performance liquid chromatography electrochemical detection method in 35 age- and sex-matched healthy subjects, 22 undialyzed patients with advanced renal failure, and 109 HD patients to assess the relation between oxidative DNA damage and complement-activating membranes, blood antioxidants, and iron status. Dialysis membranes were classified into complement-activating (cellulose; n = 55) and non-complement-activating (polymethylmethacrylate [PMMA]; n = 35; polysulfone [PS]; n = 19) membranes. We found increased oxidative stress in undialyzed and HD patients based on a decrease in plasma levels of ascorbate and alpha-tocopherol adjusted for blood lipid (alpha-tocopherol/lipid), serum albumin, and reduced glutathione levels in whole blood and an increase in oxidized glutathione levels in whole blood compared with controls (P < 0.001). The greatest 8-OHdG level in leukocyte DNA was in HD patients, followed by undialyzed patients and healthy controls (P < 0.001), and was significantly greater in HD patients using cellulose membranes than those using PMMA or PS membranes (P < 0.001). 8-OHdG levels correlated with plasma alpha-tocopherol/lipid (r = -0.314; P < 0.005), serum iron (r = 0. 446; P < 0.001), and transferrin saturation values (r = 0.202; P < 0.05) in the analysis of all HD patients. In a 6-week crossover study, 8-OHdG levels significantly decreased after the switch from cellulose to synthetic membranes for 2 weeks and increased after the shift from synthetic to cellulose membranes (P < 0.05). Iron metabolism indices and plasma alpha-tocopherol/lipid values did not change significantly in the study period. We conclude that 8-OHdG content in leukocyte DNA is a biomarker of oxidant-induced DNA damage in HD patients. Oxidative DNA damage is a consequence of uremia, further augmented by complement-activating membranes. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/11054349/8_hydroxy_2'_deoxyguanosine_of_leukocyte_DNA_as_a_marker_of_oxidative_stress_in_chronic_hemodialysis_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(00)77457-9 DB - PRIME DP - Unbound Medicine ER -