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 progre...

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Bibliographic Details
Published in:Biological & Pharmaceutical Bulletin 2009/07/01, Vol.32(7), pp.1204-1208
Main Authors: Ienaga, Kazuharu, Mikami, Hiroki, Yokozawa, Takako
Format: Article
Language:English
Subjects:
Animals
Antioxidants - chemistry
Antioxidants - therapeutic use
Biomarkers - blood
Biomarkers - urine
chronic renal failure
Creatinine - blood
Creatinine - urine
Disease Models, Animal
Disease Progression
Dose-Response Relationship, Drug
Guanidines - blood
Guanidines - urine
Hydantoins - chemistry
Hydantoins - therapeutic use
Kidney Failure, Chronic - metabolism
Kidney Failure, Chronic - prevention & control
Kidney Function Tests
Male
methylguanidine
Methylguanidine - blood
Methylguanidine - urine
NZ-419
oxidative stress
Oxidative Stress - drug effects
Rats
Rats, Wistar
Succinates - blood
Succinates - urine
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Summary: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 (CCr) in the control rats. Treatment with NZ-419 from the beginning significantly inhibited the decrease in CCr 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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.32.1204