Prevention of DNA damage in renal transplantation by losartan and enalapril: the role of renin-angiotensin system polymorphisms

Clin Exp Nephrol. 2008 Feb;12(1):65-73. doi: 10.1007/s10157-007-0001-x. Epub 2008 Jan 5.

Abstract

Background: In this study the effect of losartan and enalapril on the reduction of DNA damage was evaluated in regard to renin-angiotensin system (RAS) polymorphisms.

Methods: After determination of genotypes of RAS polymorphism by PCR, 64 renal transplant recipients were randomly allocated to one of four groups: the first and second groups were treated with E (E+: 10 mg/day) and L (L+: 50 mg/day) alone, respectively. The third group received E+L (E+L+: 10 + 50 mg/day), and the forth group received no medication (E-L-). The subjects were followed for 8 weeks. After a 2-week washout period, the E group changed to L and vice versa as a cross-over design. They were followed for another 8 weeks. Before and after treatment, we checked 8-OHdG and malondialdehyde (MDA) as biomarkers of DNA damage and lipid peroxidation, respectively.

Results: 8-OHdG levels were significantly decreased after treatment in the E+L+ and L+ groups (P < 0.001, P = 0.001, respectively). Only the TT genotype of AGT had the most antioxidative role regarding the treatment (P = 0.01). We found a remarkable correlation between MDA and DNA damage levels before and after intervention (r = 0.48, P < 0.001; r = 0.35, P = 0.006).

Conclusion: The protective effects of L+ and E+L+ on DNA breaks are surprising regarding the RAS polymorphisms.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adult
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Ataxia Telangiectasia Mutated Proteins
  • Biomarkers / blood
  • Cell Cycle Proteins / genetics
  • DNA Damage / drug effects*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / blood
  • Enalapril / therapeutic use*
  • Female
  • Humans
  • Kidney Transplantation / methods*
  • Lipid Peroxidation
  • Losartan / therapeutic use*
  • Male
  • Malondialdehyde / blood
  • Peptidyl-Dipeptidase A / genetics
  • Polymorphism, Genetic*
  • Protein Serine-Threonine Kinases / genetics
  • Renin-Angiotensin System / genetics*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Cell Cycle Proteins
  • Malondialdehyde
  • Enalapril
  • 8-Hydroxy-2'-Deoxyguanosine
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases
  • ACE protein, human
  • Peptidyl-Dipeptidase A
  • Deoxyguanosine
  • Losartan