Prevention of DNA damage in renal transplantation by losartan and enalapril: the role of renin-angiotensin system polymorphisms.
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.
Ghorbanihaghjo
Amir
A
Drug Applied Research Center (DARC), Biotechnology Research Center, Tabriz Medical University, Tabriz, Iran. ghorbaniamir@hotmail.com
Veisi
Pegah
P
Argani
Hassan
H
Aghaeishahsavari
Mohammad
M
Noroozianavval
Masood
M
Rashtchizadeh
Nadereh
N
Mesgari
Mehran
M
Safa
Javid
J
Babaei
Hosain
H
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*
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