Amelioration of diabetic microalbuminuria and lipid peroxidation by captopril.
Administration of captopril, a scavenger of oxygen derived radicals as well as an inhibitor of angiotensin converting enzyme, has been an efficient way of treating diabetic proteinuria. In the present study, we evaluate whether captopril can ameliorate diabetic proteinuria as an effect on oxidative stress in streptozotocin- induced diabetic rats (STZR). At four weeks after the injection of streptozotocin (50 mg/kg, i.v.), STZR (n = 5) exhibited microalbuminuria. The rate of urinary albumin excretion was 0.5 +/- 0.1 and 2.6 +/- 0.3 mg/24hr in age-matched control rats (CR; n = 5) and STZR, respectively. Compared to CR, STZR also showed an extremely increased rate of urinary lipid peroxides (LPO) excretion, an index of oxygen derived radicals generation. The respective values for CR and STZR were 0.6 +/- 0.3 and 6.9 +/- 0.6 mumol/24 hr. Significant amelioration of urinary albumin and LPO excretion rate by the treatment of insulin (2 U/day) suggests that these are associated with the diabetic state induced by streptozotocin rather than a direct effect of streptozotocin. Chronic administration of captopril, which did not cause any discernible effect on CR, significantly reduced the urinary albumin excretion rate and decreased LPO excretion in STZR. The urinary albumin excretion rate was significantly correlated with the LPO excretion rate (p = 0.0004). These results suggest that oxidative stress can be responsible for diabetic microalbuminuria, and captopril could diminish the lipid peroxidation and ameliorate the microalbuminuria in diabetic rats.
Ha
H
H
Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
Kim
K H
KH
D000419:Albuminuria / Q000188:drug therapy*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007328:Insulin; D002216:Captopril