Urinary Excretion of Creatol, an In Vivo Biomarker of Hydroxyl Radical, in Patients with Chronic Renal Failure

Abstract

Creatol (CTL) is a hydroxyl radical adduct of creatinine (Cr). The serum methylguanidine (MG) level and the MG/Cr molar ratio are reported to be biomarkers for oxidative stress. The aim of this study was to examine whether urinary excretion of CTL, another oxidative stress-related marker, is increased in patients with chronic renal failure (CRF). One hundred twentyfour non-dialyzed patients with chronic renal failure (serum Cr level, 1.3-10.0 mg/dL) were recruited from our hospitals. Urine and serum levels of CTL and MG were determined by high-performance liquid chromatography with the use of 9, 10-phenanthrenequinone as a fluorogenic reagent. The CTL/Cr and (CTL+MG)/Cr molar ratios in spot urine samples were also compared with those in 24-h urine samples. The urinary CTL/Cr and (CTL+MG)/Cr molar ratios increased with decreases in Cr clearance in patients with CRF. Correlations between serum and spot urine (CTL+MG)/Cr and between serum and spot urine CTL/Cr were quite similar to those in 24-h urine samples. CTL/Cr and (CTL+MG)/Cr molar ratios in both 24-h urine and spot urine samples appear to be useful indices of the severity of CRF.

Treatment with NZ-419 (5-Hydroxy-1-methylimidazoline-2,4-dione), a Novel Intrinsic Antioxidant, against the Progression of Chronic Kidney Disease at Stages 3 and 4 in Rats

“…1) In our previous paper, 3) we reported for the first time that an intrinsic antioxidant compound could prevent the initiation and/or progression of CRF: the compound investigated was NZ-419 (5-hydroxy-1-methylimidazolidine-2,4-dione, 5-hydroxy-1-methylhydantoin: HMH, CAS: 84210-26-4), [4][5][6][7][8][9] a creatinine (Cr) metabolite that prevented the initiation and/or progression of adenine-induced CRF. We chose CRF or CKD at stages equivalent to human stages 3, 4 and 5, where hydroxyl radicals are over-produced, 2,10) as one of the targets aims, 3,11,12) because NZ-419 had been shown to be a hydroxyl radical scavenger. 11,12) Meanwhile, since there is a hypothesis that oxidative stress might be a common key factor in the progression of CRF induced by several different causes, antioxidants might inhibit the progression of CRF regardless of its causes.…”

Acute kidney injury mediated by oxidative stress in Egyptian horses with exertional rhabdomyolysis

“…For total plasma protein, albumin, urea, creatinine, the used commercial test kits were supplied by Spinreact (Spinreact, Barcelona, Spain). Plasma CTL and MG were determined by high-performance liquid chromatography (HPLC) with the use of 9, 10-phenanthrenequinone as a fluorogenic reagent after deproteinization by adding trichloroacetic acid as previously described by Ienaga et al (2007). SOD and GSH-Px activities were spectrophotometrically determined from red blood cells as described by Ono et al (1990) and Williams et al (2004), respectively by using commercial test kits supplied by Randox (Randox Laboratories Ltd, UK).…”

Creatinine and HMH (5-hydroxy-1-methylhydantoin, NZ-419) as intrinsic hydroxyl radical scavengers

“…Therefore, we think it is hard to explain the mode of action of HMH only by the direct •OH radical scavenging effect. Formation of CTL from Crn both under in vitro and in vivo conditions is inhibited by HMH ( Figure 11A) (3)(4)(5)(6)(7)35,(39)(40)(41). We have noticed that its inhibition in cells is more apparent than its effect in a cell-free system and is comparable to DMSO (39).…”

“…Creatinine (Crn) is one of the main intrinsic hydroxyl radical (•OH) scavengers (1)(2)(3)(4)(5)(6)(7)(8), but this simple fact has not yet become widely accepted. One main reason might be an incorrect old belief that Crn has been taught to be an end-metabolite in mammals.…”