RGD Reference Report - Superoxide dismutase mimetic drug tempol aggravates anti-GBM antibody-induced glomerulonephritis in mice. - Rat Genome Database

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Superoxide dismutase mimetic drug tempol aggravates anti-GBM antibody-induced glomerulonephritis in mice.

Authors: Lu, H  Zhen, J  Wu, T  Peng, A  Ye, T  Wang, T  Yu, X  Vaziri, ND  Mohan, C  Zhou, XJ 
Citation: Lu H, etal., Am J Physiol Renal Physiol. 2010 Aug;299(2):F445-52. Epub 2010 May 26.
RGD ID: 6903276
Pubmed: PMID:20504883   (View Abstract at PubMed)
DOI: DOI:10.1152/ajprenal.00583.2009   (Journal Full-text)

Oxidative stress plays an important role in the pathogenesis of anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM-GN). Superoxide dismutase (SOD) is the first line of defense against oxidative stress by converting superoxide to hydrogen peroxide (H(2)O(2)). We investigated the effect of the SOD mimetic drug tempol on anti-GBM-GN in mice. 129/svJ mice were challenged with rabbit anti-mouse-GBM sera to induce GN and subsequently divided into tempol (200 mg.kg(-1).day(-1), orally) and vehicle-treated groups. Routine histology, SOD and catalase activities, malondialdehyde (MDA), H(2)O(2), and immunohistochemical staining for neutrophils, lymphocytes, macrophages, p65-NF-kappaB, and osteopontin were performed. Mice with anti-GBM-GN had significantly reduced renal SOD and catalase activities and increased H(2)O(2) and MDA levels. Unexpectedly, tempol administration exacerbated anti-GBM-GN as evidenced by intensification of proteinuria, the presence of severe crescentic GN with leukocyte influx, and accelerated mortality in the treated group. Tempol treatment raised SOD activity and H(2)O(2) level in urine, upregulated p65-NF-kappaB and osteopontin in the kidney, but had no effect on renal catalase activity. Thus tempol aggravates anti-GBM-GN by increasing production of H(2)O(2) which is a potent NF-kappaB activator and as such can intensify inflammation and renal injury. This supposition is supported by increases seen in p65-NF-kappaB, osteopontin, and leukocyte influx in the kidneys of the tempol-treated group.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
anti-basement membrane glomerulonephritis  ISOSpp1 (Mus musculus)6903276; 6903276 RGD 
anti-basement membrane glomerulonephritis  IEP 6903276 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Spp1  (secreted phosphoprotein 1)

Genes (Mus musculus)
Spp1  (secreted phosphoprotein 1)

Genes (Homo sapiens)
SPP1  (secreted phosphoprotein 1)


Additional Information