Effects of allopurinol, a xanthine oxidase inhibitor, on renal injury in hypercholesterolemia-induced hypertensive rats.
To investigate if increased lipid peroxidation is involved in hypercholesterolemia-induced hypertension and renal injury, we examined the effects of allopurinol, a xanthine oxidase inhibitor, on these conditions. Groups of male Sprague--Dawley rats were fed for 8 weeks with a high-cholesterol diet (4% cholesterol), a high-cholesterol plus allopurinol (10 mg/kgBW/day) diet or a normal diet. Systolic blood pressure (SBP), serum lipids, uric acid (UA) and malondialdehyde (MDA) as a measure of lipid peroxides, and urinary excretion of protein (UP) were measured after 0, 4 and 8 weeks. Urinary excretion of nitrite plus nitrate (UNOx) and iron (UFe), and MDA in the kidney were measured after 8 weeks. The renal injury was evaluated by the glomerular sclerosis score (SS). The high-cholesterol diet increased SBP, serum total cholesterol and UA, MDA in the serum and kidney, UP, UNOx, UFe and SS. Allopurinol ameliorated cholesterol-induced elevation in serum UA, MDA in the serum and kidney, UP, UNOx, UFe and SS, but did not affect SBP. Hence, our results suggest that lipid peroxidation may be involved in hypercholesterolemia-induced renal injury, and that suppression of lipid peroxidation can reduce such injury.
Minami
Mayumi
M
Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo Metropolitan Police Hospital, Tokyo, Japan. mayuminami@ aol.com
Ishiyama
Akihiro
A
Takagi
Masao
M
Omata
Masao
M
Atarashi
Keiichiro
K
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000502:physiology; D006937:Hypercholesterolemia / Q000150:complications*; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control*; D007501:Iron / Q000652:urine; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D008315:Malondialdehyde / Q000652:urine; D009569:Nitric Oxide / Q000652:urine; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D014280:Triglycerides; D014527:Uric Acid; D009569:Nitric Oxide; D008315:Malondialdehyde; D000493:Allopurinol; D002784:Cholesterol; D003404:Creatinine; D007501:Iron; D014969:Xanthine Oxidase