DNA damage of lymphocytes in experimental chronic renal failure: Beneficial effects of losartan

Background. Kidney diseases are associated with the accumulation of various uremic toxins increasing the oxygen free radical (OFR) activity with a num ber of serious consequences. One of them could be the impairment of DNA sta bility with the increased formation of DNA breaks. Methods. The study was performed in 4/6 kidney ablation rat nephropathy las ting for three months. The results of sham-operated (Sham), remnant kidney (Nx), and Nx treated by losartan (NxL) were compared. Results. Nx significantly increased blood pressure, plasma creatinine, urea , hippurate, malondialdehyde (MDA), lipofuscin (LF), and the number of DNA breaks of lymphocytes. Losartan decreased the rise of blood pressure and in hibited the rise of creatinine plasma concentration but not of other variab les, while it markedly inhibited the number of DNA breaks (Sham 15.9 +/- 1. 1, Nx 54.5 +/- 1.7, P < 0.001; Nx/Sham, NxL 23.3 +/- 2.6 P < 0.001, NxL/Sha m and P < 0.001 NxL/Nx). Conclusions. The 4/6 kidney ablation nephropathy increases the susceptibili ty of lymphocyte DNA to breaks, and losartan inhibits the number of breaks by a mechanism independent on glomerular filtration, accumulation of MDA or LF (markers of oxidative stress), and hippurate (marker of the accumulatio n of middle molecular substances). An independent mechanism, probably the i nterference with proliferation, is suggested.