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

Author(s): Ghorbanihaghjo A, Veisi P, Argani H, Aghaeishahsavari M, Noroozianavval M, Rashtchizadeh N, Mesgari M, Safa J, Babaei H

Affiliation(s): Drug Applied Research Center (DARC), Biotechnology Research Center, Tabriz Medical University, Tabriz, Iran. ghorbaniamir@hotmail.com

Publication date & source: 2008-02, Clin Exp Nephrol., 12(1):65-73. Epub 2008 Jan 5.

Publication type: Research Support, Non-U.S. Gov't

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.

Page last updated: 2008-03-26

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