American Journal of Nephrology
Original Report: Laboratory Investigation
A Novel Nuclear Factor κB Inhibitor, Dehydroxymethylepoxyquinomicin, Ameliorates Puromycin Aminonucleoside-Induced Nephrosis in MiceShimo T.a · Adachi Y.b, c · Yamanouchi S.a · Tsuji S.a · Kimata T.a · Umezawa K.d · Okigaki M.e · Takaya J.a · Ikehara S.c · Kaneko K.aaDepartment of Pediatrics, Kansai Medical University, Osaka, bDivision of Clinical Pathology, Toyooka Hospital, Hyogo, cDepartment of Stem Cell Disorders, Kansai Medical University, Osaka, dDepartment of Molecular Target Medicine Screening, Aichi Medical University School of Medicine, Aichi, and eDepartment of Cardiovascular and Renal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Article / Publication Details
Received: October 27, 2012
Accepted: February 08, 2013
Published online: March 19, 2013
Issue release date: April 2013
Number of Print Pages: 8
Number of Figures: 7
Number of Tables: 0
ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)
For additional information: https://www.karger.com/AJN
Abstract
Background/Aims: Minimal-change nephrotic syndrome (MCNS) is a kidney disease defined by selective proteinuria and hypoalbuminemia occurring in the absence of cellular glomerular infiltrates or immunoglobulin deposits. Recent observations suggest that nuclear factor κB (NF-κB) of podocyte is strongly associated with the development of proteinuria in MCNS. Dehydroxymethylepoxyquinomicin (DHMEQ) is a novel NF-κB inhibitor that potently inhibits DNA-binding activity of NF-κB, resulting in several therapeutic effects in various pathological conditions. We conducted this study to ask whether DHMEQ may ameliorate the nephrosis in mice induced by puromycin aminonucleoside (PAN), which is considered to be an animal model for MCNS. Methods/Results: Pretreatment with DHMEQ alleviated the proteinuria and reversed the serum abnormalities in mice nephrosis induced by 450 mg/kg of PAN. Increased serum interleukin-6 level in PAN-induced nephrosis was also completely suppressed by DHMEQ. Electron microscopic analyses of glo-meruli indicated that DHMEQ can inhibit the podocyte foot process effacement via blocking the translocation of podocyte NF-κB from cytoplasm to nucleus. Conclusions: These results suggest that DHMEQ can be a potential therapeutic agent for MCNS.
© 2013 S. Karger AG, Basel
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Article / Publication Details
Received: October 27, 2012
Accepted: February 08, 2013
Published online: March 19, 2013
Issue release date: April 2013
Number of Print Pages: 8
Number of Figures: 7
Number of Tables: 0
ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)
For additional information: https://www.karger.com/AJN
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