Ghorbanihaghjo Amir, Veisi Pegah, Argani Hassan, Aghaeishahsavari Mohammad, Noroozianavval Masood, Rashtchizadeh Nadereh, Mesgari Mehran, Safa Javid, Babaei Hosain
Drug Applied Research Center (DARC), Biotechnology Research Center, Tabriz Medical University, Tabriz, Iran.
Clin Exp Nephrol. 2008 Feb;12(1):65-73. doi: 10.1007/s10157-007-0001-x. Epub 2008 Jan 5.
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.
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.
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).
The protective effects of L+ and E+L+ on DNA breaks are surprising regarding the RAS polymorphisms.
在本研究中，针对肾素 - 血管紧张素系统（RAS）多态性，评估了氯沙坦和依那普利对减少DNA损伤的作用。
通过聚合酶链反应（PCR）确定RAS多态性的基因型后，将64名肾移植受者随机分为四组之一：第一组和第二组分别单独接受依那普利（E +：10毫克/天）和氯沙坦（L +：50毫克/天）治疗。第三组接受依那普利+氯沙坦（E + L +：10 + 50毫克/天），第四组不接受药物治疗（E - L -）。对受试者进行8周的随访。经过2周的洗脱期后，采用交叉设计，E组改为服用氯沙坦，L组改为服用依那普利。再对他们进行8周的随访。治疗前后，我们分别检测了作为DNA损伤和脂质过氧化生物标志物的8 - 羟基脱氧鸟苷（8 - OHdG）和丙二醛（MDA）。
E + L +组和L +组治疗后8 - OHdG水平显著降低（分别为P < 0.001，P = 0.001）。仅AGT的TT基因型在治疗方面具有最强的抗氧化作用（P = 0.01）。我们发现干预前后MDA与DNA损伤水平之间存在显著相关性（r = 0.48，P < 0.001；r = 0.35，P = 0.006）。
就RAS多态性而言，L +和E + L +对DNA断裂的保护作用令人惊讶。
