Urinary excretion of biomarkers of oxidative kidney damage induced by ferric nitrilotriacetate.
There is an increasing need for biomarkers of oxidative stress in animals and man. In this study, we have evaluated in the rat the utility of various endogenous products that are excreted in urine as potential noninvasive biomarkers of oxidative stress in the kidney. Renal oxidative damage was induced by daily i.p. injections of ferric nitrilotriacetate (Fe-NTA) for a period of 13 days. The daily dose of Fe-NTA was increased during the experiment from 6 to 40 mg Fe/kg body wt. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), coproporphyrin III (COPRO III), seven aldehydes, and acetone were determined in fractionated urine samples and compared with commonly used urinary and plasma clinical chemical parameters for toxicity. The parameters that showed the earliest increase were acetaldehyde (ACET), propanal (PROPA), and COPRO III. Their increase was significantly earlier than that of classical clinical chemical parameters indicative of renal damage such as urinary concentration of glucose (GLU) and protein (PRT), and N-acetyl-beta-D-glucosaminidase (NAG) activity. The excretion of 8-OHdG was increased only after administration of the highest dose of Fe-NTA. Urinary excretion of acetone, form-aldehyde (FOR), butanal (BUTA), pentanal (PENTA) hexanal (HEXA), and malondialdehyde (MDA) was also increased; however, their increase occurred only slightly before or simultaneously with that of the urinary clinical chemical parameters. In conclusion, 8-OHdG, acetone, FOR, BUTA, PENTA, HEXA, and MDA may possibly serve as biomarkers for oxidative kidney damage. COPRO III, ACET, and PROPA might even be used as biomarkers of production of reactive oxygen species at an early stage.
Leiden/Amsterdam Center for Drug Research, Division of Toxicology, Leiden University, The Netherlands.
R C
RC
Hermanns
L L
LL
de Zwart
P J
PJ
Salemink
J N
JN
Commandeur
N P
NP
Vermeulen
J H
JH
Meerman
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D003306:Coproporphyrins / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D005290:Ferric Compounds / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008054:Lipid Peroxides / Q000652:urine; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D003306:Coproporphyrins; D005290:Ferric Compounds; D008054:Lipid Peroxides; C026971:coproporphyrin III; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate