RGD Reference Report - Diquat induces renal proximal tubule injury in glutathione reductase-deficient mice. - Rat Genome Database

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Diquat induces renal proximal tubule injury in glutathione reductase-deficient mice.

Authors: Rogers, LK  Bates, CM  Welty, SE  Smith, CV 
Citation: Rogers LK, etal., Toxicol Appl Pharmacol. 2006 Dec 15;217(3):289-98. Epub 2006 Sep 26.
RGD ID: 7257555
Pubmed: PMID:17078987   (View Abstract at PubMed)
DOI: DOI:10.1016/j.taap.2006.08.012   (Journal Full-text)

Reactive oxygen species (ROS) have been associated with many human diseases, and glutathione (GSH)-dependent processes are pivotal in limiting tissue damage. To test the hypothesis that Gr1(a1Neu) (Neu) mice, which do not express glutathione reductase (GR), would be more susceptible than are wild-type mice to ROS-mediated injury, we studied the effects of diquat, a redox cycling toxicant. Neu mice exhibited modest, dose- and time-dependent elevations in plasma alanine aminotransferase (ALT) activities, 126+/-36 U/l at 2 h after 5 micromol/kg of diquat, but no ALT elevations were observed in diquat-treated C3H/HeN mice for up to 6 h after 50 micromol/kg of diquat. Histology indicated little or no hepatic necrosis in diquat-treated mice of either strain, but substantial renal injury was observed in diquat-treated Neu mice, characterized by brush border sloughing in the proximal tubules by 1 h and tubular necrosis by 2 h after doses of 7.5 micromol/kg. Decreases in renal GSH levels were observed in the Neu mice by 2 h post dose (3.4+/-0.4 vs 0.2+/-0.0 micromol/g tissue at 0 and 50 micromol/kg, respectively), and increases in renal GSSG levels were observed in the Neu mice as early as 0.5 h after 7.5 micromol/kg (105.5+/-44.1 vs 27.9+/-4.8 nmol/g tissue). Blood urea nitrogen levels were elevated by 2 h in Neu mice after doses of 7.5 micromol/kg (Neu vs C3H, 32.8+/-4.1 vs 17.9+/-0.3 mg/dl). Diquat-induced renal injury in the GR-deficient Neu mice offers a useful model for studies of ROS-induced renal necrosis and of the contributions of GR in defense against oxidant-mediated injuries in vivo.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acute kidney tubular necrosis  ISOGsr (Mus musculus)7257555; 7257555 RGD 
acute kidney tubular necrosis  IMP 7257555 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gsr  (glutathione-disulfide reductase)

Genes (Mus musculus)
Gsr  (glutathione reductase)

Genes (Homo sapiens)
GSR  (glutathione-disulfide reductase)


Additional Information