title: Excretion of multiple urinary biomarkers for radical induced damage in rats treated with three different nephrotoxic compounds.
abstract: In the present study the urinary excretion of seven aldehydes, acetone and coproporphyrin III as non-invasive in vivo biomarkers of free radical damage was measured in rats after treatment with three nephrotoxic compounds: cisplatin, mercuric chloride (HgCl2) and N -acetyl- S -(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFE-Nac). A clear difference between the different nephrotoxic compounds was found in the time interval between dosage and maximal toxicity, as measured by clinical chemical parameters in urine. In rats treated with TFE-Nac and HgCl2 this was fast: 12 h and 24 h after treatment, respectively. In the rats treated with cisplatin, however, nephrotoxicity occurred later: 96 h-108 h after treatment. Urinary creatinine excretion was decreased in all treatments. Therefore, the excretion of the proposed biomarkers was expressed as amount excreted per 12 h urine fraction as well as amount excreted per mol creatinine in each 12 h urine fraction. Urinary excretion of coproporphyrin III was decreased in almost all 12 h urine fractions with all treatments, however, when expressed per mol creatinine, increases were found in urine of rats treated with cisplatin and HgCl2. In cisplatin-treated rats an increase was found in the excretion of formaldehyde per 12 h, but acetaldehyde, propanal and MDA levels were decreased. Expressed per mol creatinine, MDA levels were decreased, but other aldehydes were increased. In HgCl2-treated rats urinary aldehyde excretion expressed per mol creatinine was increased. In TFE-Nac treated animals the urinary levels of acetaldehyde per 12 h were increased and per mol creatinine the levels of some aldehydes were only slightly increased. With none of the treatments did the increase in the biomarkers expressed per mol creatinine exceed the decrease in creatinine excretion. Similar time intervals were found between dosage and maximal excretion of biomarkers as for the time intervals between dosage and maximal toxicity. With all treatments significant increases in the excretion of acetone were found both per 12 h and per mol creatinine, probably related to the increased glucose excretion. It was concluded that no convincing evidence for free radical damage was found in the present study with the employed biomarkers.
authors.forename: L L
authors.initials: LL
authors.lastname: De Zwart
authors.forename: R C
authors.initials: RC
authors.lastname: Hermanns
authors.forename: J H
authors.initials: JH
authors.lastname: Meerman
authors.forename: J N
authors.initials: JN
authors.lastname: Commandeur
authors.forename: P J
authors.initials: PJ
authors.lastname: Salem Ink
authors.forename: N P
authors.initials: NP
authors.lastname: Vermeulen