CKDdb-logoCKDdb - Study ID Exp23506792a

PubMed ID23506792
Authorsvan Swelm RP, Laarakkers CM, Pertijs JC, Verweij V, Masereeuw R, Russel FG.
TitleUrinary proteomic profiling reveals diclofenac-induced renal injury and hepatic regeneration in mice.
JournalToxicol Appl Pharmacol. 2013 Jun 1;269(2):141-9.
AbstractDiclofenac (DF) is a widely used non-steroidal anti-inflammatory drug for the treatment of rheumatic disorders, but is often associated with liver injury. We applied urinary proteomic profiling using MALDI-TOF MS to identify biomarkers for DF-induced hepatotoxicity in mice. Female CH3/HeOUJIco mice were treated with 75mg/kg bw DF by oral gavage and 24h urine was collected. Proteins identified in urine of DF-treated mice included epidermal growth factor, transthyretin, kallikrein, clusterin, fatty acid binding protein 1 and urokinase, which are related to liver regeneration but also to kidney injury. Both organs showed enhanced levels of oxidative stress (TBARS, p<0.01). Kidney injury was confirmed by histology and increased Kim1 and Il-6 mRNA expression levels (p<0.001 and p<0.01). Liver histology and plasma ALT levels in DF-treated mice were not different from control, but mRNA expression of Stat3 (p<0.001) and protein expression of PCNA (p<0.05) were increased, indicating liver regeneration. In conclusion, urinary proteome analysis revealed that DF treatment in mice induced kidney and liver injury. Within 24h, however, the liver was able to recover by activating tissue regeneration processes. Hence, the proteins found in urine of DF-treated mice represent kidney damage rather than hepatic injury.

Sample characteristics

SpeciesTissue / SourceCompartmentDiseaseNDetection method
Mus musculusurinewholeDiclofenac_induced10MALDI-TOF MS

Sample description and preparation

N (case)5
N (control)5
Disease (case)diclofenac-induced renal injury
Disease inductionDiclofenac (75 mg/kg), 24h
Digestin-solution digestion LysC, trypsin

Molecule list

Molecule IDextExternal IDGeneNameSource accScores
A1497XUROK_MOUSEPlauUrokinase-type plasminogen activatorNP_032899.1p-value: < 0.05
A6853XKLK1_MOUSEKlk1Kallikrein-1NP_034769.4p-value: < 0.05
A1276XCLUS_MOUSECluClusterinNP_038520.2p-value: < 0.05
A979B FABPL_MOUSEFabp1Fatty acid-binding proteinNP_059095.1p-value: < 0.05

Compile date 08-10-2018© iMODE-CKD consortium