Effects of ramipril in nondiabetic nephropathy: improved parameters of oxidatives stress and potential modulation of advanced glycation end products.
Enhanced oxidative stress is involved in the progression of renal disease. Since angiotensin converting enzyme inhibitors (ACEI) have been shown to improve the antioxidative defence, we investigated, in patients with nondiabetic nephropathy, the short-term effect of the ACEI ramipril on parameters of oxidative stress, such as advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), homocysteine (Hcy), and lipid peroxidation products. Ramipril (2.5-5.0 mg/day) was administered to 12 newly diagnosed patients for 2 months and data compared with a patient group under conventional therapy (diuretic/beta-blockers) and with age- and sex-matched healthy subjects (CTRL). Patients had mild to moderate renal insufficiency and showed, in the plasma, higher fluorescent AGE and carboxymethyllysine (CML) levels, as well as elevated concentrations of AOPPs, lipofuscin and Hcy when compared with CTRL. Basal data of the patients on conventional therapy did not differ significantly from the ramipril group, except for higher Hcy levels in the latter. Administration of ramipril resulted in a drop in blood pressure and proteinuria, while creatinine clearance remained the same. The fluorescent AGEs exhibited a mild but significant decline, yet CML concentration was unchanged. The AOPP and malondialdehyde concentrations decreased, while a small rise in neopterin levels was evident after treatment. The mentioned parameters were not affected significantly in the conventionally treated patients. Evidence that ramipril administration results in a mild decline of fluorescent AGEs is herein presented for the first time. The underlying mechanism may be decreased oxidative stress, as indicated by a decline in AOPPs and malondialdehyde.
Sebeková
K
K
Institute of Preventive and Clinical Medicine, Bratislava, Slovakia. sebekova@upkm.sk
Gazdíková
K
K
Syrová
D
D
Blazícek
P
P
Schinzel
R
R
Heidland
A
A
Spustová
V
V
Dzúrik
R
R
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003404:Creatinine / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006710:Homocysteine / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D007690:Polycystic Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017257:Ramipril / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013223:Statistics as Topic; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D001786:Blood Glucose; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D017127:Glycation End Products, Advanced; D008062:Lipofuscin; D006710:Homocysteine; D008315:Malondialdehyde; C048496:N(6)-carboxymethyllysine; D003404:Creatinine; D008239:Lysine; D017257:Ramipril