First indications demonstrating the preventive effects of NZ-419, a novel intrinsic antioxidant, on the initiation and/or progression of chronic renal failure in rats.
The concentration of NZ-419 (5-hydroxy-1-methylimidazolidine-2,4-dione), an intrinsic antioxidant, has been shown to increase in the sera of animals and patients with chronic renal failure (CRF). This is the first report that orally administered exogenous NZ-419 prevents the initiation and/or progression of CRF in rats using an adenine-loaded model. After 24 d of adenine loading, there was a ca. 90% decrease in creatinine clearance (C(Cr)) in the control rats. Treatment with NZ-419 from the beginning significantly inhibited the decrease in C(Cr) and also the increase in serum creatinine (sCr). Bio-markers for in vivo hydroxyl radicals, the serum methylguanidine (sMG) level, and sMG/sCr molar ratio, not only in serum but also in the urine, kidney, liver, and muscle indicated that NZ-419 inhibited the increase in oxidative stress induced by CRF in rats. An increase of guanidinosuccinic acid, an another bio-marker of oxidative stress, was also inhibited with NZ-419.
Ienaga
Kazuharu
K
Nippon Zoki Pharmaceutical Co., Ltd.
Mikami
Hiroki
H
Yokozawa
Takako
T
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000097:blood / Q000652:urine; D006827:Hydantoins / Q000737:chemistry / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D008760:Methylguanidine / Q000097:blood / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates / Q000097:blood / Q000652:urine
D000975:Antioxidants; D015415:Biomarkers; D006146:Guanidines; D006827:Hydantoins; D013386:Succinates; D008760:Methylguanidine; C001318:guanidinosuccinic acid; C058007:5-hydroxy-1-methylhydantoin; D003404:Creatinine