Urinary excretion of biomarkers of oxidative kidney damage induced by ferric nitrilotriacetate. 1998

R C Hermanns, and L L de Zwart, and P J Salemink, and J N Commandeur, and N P Vermeulen, and J H Meerman
Leiden/Amsterdam Center for Drug Research, Division of Toxicology, Leiden University, The Netherlands.

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.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008054 Lipid Peroxides Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. Fatty Acid Hydroperoxide,Lipid Peroxide,Lipoperoxide,Fatty Acid Hydroperoxides,Lipid Hydroperoxide,Lipoperoxides,Acid Hydroperoxide, Fatty,Acid Hydroperoxides, Fatty,Hydroperoxide, Fatty Acid,Hydroperoxide, Lipid,Hydroperoxides, Fatty Acid,Peroxide, Lipid,Peroxides, Lipid
D008297 Male Males
D009571 Nitrilotriacetic Acid A derivative of acetic acid, N(CH2COOH)3. It is a complexing (sequestering) agent that forms stable complexes with Zn2+. (From Miall's Dictionary of Chemistry, 5th ed.) Aluminum Nitrilotriacetate,Dysprosium Nitrilotriacetate,Trisodium Nitrilotriacetate,Acid, Nitrilotriacetic,Nitrilotriacetate, Aluminum,Nitrilotriacetate, Dysprosium,Nitrilotriacetate, Trisodium
D003306 Coproporphyrins Porphyrins with four methyl and four propionic acid side chains attached to the pyrrole rings. Elevated levels of Coproporphyrin III in the urine and feces are major findings in patients with HEREDITARY COPROPORPHYRIA.
D003849 Deoxyguanosine A nucleoside consisting of the base guanine and the sugar deoxyribose.
D005290 Ferric Compounds Inorganic or organic compounds containing trivalent iron. Compounds, Ferric
D000080242 8-Hydroxy-2'-Deoxyguanosine Common oxidized form of deoxyguanosine in which C-8 position of guanine base has a carbonyl group. 2'-Deoxy-7,8-Dihydro-8-Oxoguanosine,2'-Deoxy-8-Hydroxyguanosine,2'-Deoxy-8-Oxo-7,8-Dihydroguanosine,2'-Deoxy-8-Oxoguanosine,7,8-Dihydro-8-Oxo-2'-Deoxyguanosine,7-Hydro-8-Oxodeoxyguanosine,8-Hydroxydeoxyguanosine,8-Oxo-2'-Deoxyguanosine,8-Oxo-7,8-Dihydro-2'-Deoxyguanosine,8-Oxo-7,8-Dihydrodeoxyguanosine,8-Oxo-7-Hydrodeoxyguanosine,8-Oxo-Deoxyguanosine,8OHdG,8-OH-dG,8-oxo-dG,8-oxo-dGuo,8-oxodG,8-oxodGuo,2' Deoxy 7,8 Dihydro 8 Oxoguanosine,2' Deoxy 8 Hydroxyguanosine,2' Deoxy 8 Oxo 7,8 Dihydroguanosine,2' Deoxy 8 Oxoguanosine,7 Hydro 8 Oxodeoxyguanosine,7,8 Dihydro 8 Oxo 2' Deoxyguanosine,8 Hydroxy 2' Deoxyguanosine,8 Hydroxydeoxyguanosine,8 Oxo 2' Deoxyguanosine,8 Oxo 7 Hydrodeoxyguanosine,8 Oxo 7,8 Dihydro 2' Deoxyguanosine,8 Oxo 7,8 Dihydrodeoxyguanosine,8 Oxo Deoxyguanosine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune

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