Estimation of hydroxyl radical scavenging capacity in human and rats

Abstract

Creatinine (Cr) is one of the main intrinsic hydroxyl radical (•OH) scavengers. We estimated how much Cr could scavenge •OH in human and rats, and compared such estimated values with corresponding ones for well-known deoxyguanosine (dG). Daily urinary excretions of some reaction products with •OH have been used to estimate the amount of •OH produced daily. For such a purpose, we have used Cr-related metabolites such as creatol (CTL: 5-hydroxycreatinine), an •OH adduct of Cr, plus its metabolite, methylguanidine (MG), and/or their molar sum (CTL + MG), whereas the amount of 8-hydroxydeoxyguanosine (8-OHdG), a well-known marker of •OH, in the body is negligible (103-fold less than Cr-related metabolites). The daily amounts of •OH scavenged in healthy subjects and normal rats are steady: Cr scavenges circa (ca.) 20-25 μmole and ca. 200 pmole of •OH, respectively; (CTL + MG)/Cr has been reported to be ca. 2.2 and 3.0 mmole/mole (spot urine or 24-h urine); 0.2 and 0.3% of Cr in healthy subjects are used in order to scavenge •OH, respectively. In patients with chronic renal failure (CRF) or chronic kidney disease (CKD) at stages 3-5 (glomerular filtration rate <60 mL/min/1.73 m³), •OH levels increase in proportion to the severity of CKD: up to ca. 3% of Cr is used daily in order to scavenge •OH. Novel intrinsic and natural •OH scavengers, such as 5-hydroxy-1-methylhydantoin and magnesium lithospermate B, respectively, decrease the amount of •OH, and prevent the progression of CRF in rats.