Genomic damage in chronic renal failure--potential therapeutic interventions.
In end-stage renal failure, genomic damage is enhanced. This has been shown both in the predialysis and dialysis phase by various biomarkers, such as micronuclei frequency and single cell gel electrophoresis in lymphocytes as well as with 8-hydroxy-2'-deoxyguanosine in leukocytes. There are also data about mitochondrial DNA deletions and chromosomal abnormalities. Genomic damage may be induced by a multitude of toxic factors and mutagens, in particular via enhanced generation of reactive oxygen species. In in vitro studies, incubation of tubular cells with various AGEs (carboxymethyllysine-BSA, AGE-BSA, and methylglyoxal-BSA) and angiotensin II resulted in a marked DNA damage. Coincubation with various antioxidants as well as the angiotensin II receptor blocker, candesartan, suppressed the toxic action. Moreover, an improved uremic state by daily hemodialysis ameliorated the genomic damage in lymphocytes, as compared to patients on conventional hemodialysis.
Stopper
Helga
H
Department of Pharmacology and Toxicology, University of Wuerzburg, Wuerzburg, Germany.
Schupp
Nicole
N
Klassen
André
A
Sebekova
Katarina
K
Heidland
August
A
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000975:Antioxidants / Q000008:administration & dosage; D002869:Chromosome Aberrations; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004272:DNA, Mitochondrial; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D017353:Gene Deletion; D017127:Glycation End Products, Advanced; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000628:therapy*; D048629:Micronuclei, Chromosome-Defective; D006435:Renal Dialysis; D012854:Sister Chromatid Exchange
D000975:Antioxidants; D004272:DNA, Mitochondrial; D017127:Glycation End Products, Advanced; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine