In:
Arthritis & Rheumatism, Wiley, Vol. 64, No. 1 ( 2012-01), p. 232-242
Abstract:
Accelerated severe lupus nephritis (ASLN), with an acute onset of severe clinical manifestations and histopathologic renal lesions, may represent transformation of mild LN to a severe form of glomerulonephritis. Abnormal activation of T and B cells and/or oxidative stress may play a major role in the pathogenesis of ASLN. This study tested the hypothesis that antroquinonol, a purified compound and major effective component of Antrodia camphorata with antiinflammatory and antioxidant activities, might prevent the transformation of mild LN into higher‐grade (severe) nephritis in a murine lupus model. Methods Experimental ASLN was induced in (NZB × NZW)F 1 mice by twice weekly intraperitoneal injections of Salmonella ‐type lipopolysaccharide (LPS). Starting 2 days after the first dose of LPS, mice were treated daily with antroquinonol, administered by gavage, for different durations up to 5 weeks. Results Antroquinonol administration significantly ameliorated the proteinuria, hematuria, impairment of renal function, and development of severe renal lesions, especially cellular crescent formation, neutrophil infiltration, fibrinoid necrosis, and T cell proliferation in the glomerulus, as well as periglomerular interstitial inflammation. Mechanistic analyses revealed that antroquinonol 1) inhibited T cell activation/proliferation, but enhanced Treg cell suppression and reduced renal production of interleukin‐18 (IL‐18); 2) inhibited production of reactive oxygen species and nitric oxide, but increased activation of Nrf2 in the kidney; and 3) suppressed renal inflammation via blocking of NF‐κB activation. Conclusion Antroquinonol may have therapeutic potential for the early treatment of ASLN via its differential regulation of T cell function and lowering of IL‐18 production, but also via the promotion of Nrf2 activation.
Type of Medium:
Online Resource
ISSN:
0004-3591
,
1529-0131
Language:
English
Publisher:
Wiley
Publication Date:
2012
detail.hit.zdb_id:
2014367-9
detail.hit.zdb_id:
2754614-7
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