URINARY-EXCRETION OF BIOMARKERS OF OXIDATIVE KIDNEY DAMAGE-INDUCED BYFERRIC NITRILOTRIACETATE

There is an increasing need for biomarkers of oxidative stress in anim als and man. In this study, we have evaluated in the rat the utility o f various endogenous products that are excreted in urine as potential noninvasive biomarkers of oxidative stress in the kidney. Renal oxidat ive damage was induced by daily ip injections of ferric nitrilotriacet ate (Fe-NTA) for a period of 13 days. The daily dose of Fe-NTA was inc reased during the experiment from 6 to 40 mg Fe/kg body wt. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), coproporphyrin III (COPRO II I), seven aldehydes, and acetone were determined in fractionated urine samples and compared with commonly used urinary and plasma clinical c hemical parameters for toxicity. The parameters that showed the earlie st increase were acetaldehyde (ACET), propanal (PROPA), and COPRO III. Their increase was significantly earlier than that of classical clini cal chemical parameters indicative of renal damage such as urinary con centration of glucose (GLU) and protein (PRT), and N-acetyl-beta-D-glu cosaminidase (NAG) activity. The excretion of 8-OHdG was increased onl y after administration of the highest dose of Fe-NTA. Urinary excretio n of acetone, formaldehyde (FOR), butanal (BUTA), pentanal (PENTA) hex anal (HEXA), and malondialdehyde (MDA) was also increased; however, th eir increase occurred only slightly before or simultaneously with that of the urinary clinical chemical parameters. In conclusion, 8-OHdG, a cetone, FOR, BUTA, PENTA, HEXA, and MDA may possibly serve as biomarke rs for oxidative kidney damage. COPRO III, ACET, and PROPA might even be used as biomarkers of production of reactive oxygen species at an e arly stage. (C) 1998 Society of Toxicology.