Daily hydroxyl radical scavenging capacity of mammals.
Drug Discov Ther
; 8(2): 71-5, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24815581
ABSTRACT
Both the formation and reactions of hydroxyl radical (â¢OH) are quantitative chemical reactions even in mammalians, and so we can reproduce such in vivo reactions in test tubes. Daily urinary excretions of some reaction products have been used to estimate the amount of â¢OH produced daily. Although urinary 8-hydroxydeoxyguanosine (8-OHdG) is a well-known marker of â¢OH, we have shown that creatol (CTL 5-hydroxycreatinine), an â¢OH adduct of creatinine (Crn), and its metabolite, methylguanidine (MG), are better markers, because the amount of â¢OH scavenged by deoxyguanosine (dG) in the body is negligible. We measured CTL and MG together with Crn in 24-h urine, and calculated their molar sum, CTL + MG, providing a daily estimate of moles of â¢OH scavenged with Crn, and, from the molar ratio (CTL + MG)/Crn, we can calculate the percentage of Crn that was used to scavenge â¢OH. Healthy subjects and normal rats were indicated to use circa (ca.) 0.2 and 0.3% of Crn in order to scavenge â¢OH, respectively, because the corresponding ratios, scavenged â¢OH/Crn, were 2.2 and 3.0 mmole/mole (24-h urine) (Crn scavenged ca. 20-25 µmole and ca. 200 pmole of â¢OH in healthy subjects and normal rats, respectively). Since 8-OHdG/Crn has been reported to be 1.9 µmole/mole (24-h urine), the daily scavenging capacity with Crn is 10(3)-fold more than dG. In patients with chronic renal failure (CRF) or chronic kidney disease (CKD) at stages 3-5 glomerular filtration rate (GFR) < 60 mL/min/1.73 m(2), â¢OH levels increased in proportion to the severity of CKD up to ca. 3% of Crn was used daily in order to scavenge â¢OH. Although the accumulation of MG in organs has not been reported except for the brain and skin tissues in normal animals, â¢OH increases markedly and MG becomes detectable in all organs such as the kidney, liver, and heart in CRF rats.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sequestradores de Radicais Livres
/
Radical Hidroxila
/
Rim
/
Falência Renal Crônica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Drug Discov Ther
Ano de publicação:
2014
Tipo de documento:
Article
País de publicação:
JAPAN
/
JAPON
/
JAPÃO
/
JP