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 number of serious consequences. One of them could be the impairment of DNA stability with the increased formation of DNA breaks.


METHODS
The study was performed in 4/6 kidney ablation rat nephropathy lasting 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 inhibited the rise of creatinine plasma concentration but not of other variables, 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/Sham and P < 0.001 NxL/Nx).


CONCLUSIONS
The 4/6 kidney ablation nephropathy increases the susceptibility 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 accumulation of middle molecular substances). An independent mechanism, probably the interference with proliferation, is suggested.
Krivosíková
Z
Z
Department of Pharmacotherapy, and Institutes of Preventive and Clinical Medicine, Hospital of the Ministry of Defense, Bratislava, Slovak Republic. krivosikova@upkm.sk
Dusinská
M
M
Spustová
V
V
Sebeková
K
K
Blazícek
P
P
Heidland
A
A
Dzúrik
R
R
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D015415:Biomarkers; D003404:Creatinine / Q000097:blood; D004249:DNA Damage; D005609:Free Radicals / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2
D057911:Angiotensin Receptor Antagonists; D015415:Biomarkers; D005609:Free Radicals; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D003404:Creatinine; D019808:Losartan