title: Prevention of DNA damage in renal transplantation by losartan and enalapril: the role of renin-angiotensin system polymorphisms.
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).
  
  
  CONCLUSIONS
  The protective effects of L+ and E+L+ on DNA breaks are surprising regarding the RAS polymorphisms.
authors.affiliation: Drug Applied Research Center (DARC), Biotechnology Research Center, Tabriz Medical University, Tabriz, Iran. ghorbaniamir@hotmail.com
authors.forename: Amir
authors.initials: A
authors.lastname: Ghorbanihaghjo
authors.forename: Pegah
authors.initials: P
authors.lastname: Veisi
authors.forename: Hassan
authors.initials: H
authors.lastname: Argani
authors.forename: Mohammad
authors.initials: M
authors.lastname: Aghaeishahsavari
authors.forename: Masood
authors.initials: M
authors.lastname: Noroozianavval
authors.forename: Nadereh
authors.initials: N
authors.lastname: Rashtchizadeh
authors.forename: Mehran
authors.initials: M
authors.lastname: Mesgari
authors.forename: Javid
authors.initials: J
authors.lastname: Safa
authors.forename: Hosain
authors.initials: H
authors.lastname: Babaei
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D064007:Ataxia Telangiectasia Mutated Proteins; D015415:Biomarkers / Q000097:blood; D018797:Cell Cycle Proteins / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000379:methods*; D015227:Lipid Peroxidation; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D018797:Cell Cycle Proteins; D008315:Malondialdehyde; D004656:Enalapril; D000080242:8-Hydroxy-2'-Deoxyguanosine; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D003849:Deoxyguanosine; D019808:Losartan