A Novel Nuclear Factor kappa B Inhibitor, Dehydroxymethylepoxyquinomicin, Ameliorates Puromycin Aminonucleoside-Induced Nephrosis in Mice

作者：Shimo Tomohiko; Adachi Yasushi; Yamanouchi Sohsaku; Tsuji Shoji; Kimata Takahisa; Umezawa Kazuo; Okigaki Mitsuhiko; Takaya Junji; Ikehara Susumu; Kaneko Kazunari^*

来源：American Journal of Nephrology, 2013, 37(4): 302-309.

DOI：10.1159/000348803

• Dehydroxymethylepoxyquinomicin
• Idiopathic nephrotic syndrome
• Mice
• Minimal-change nephrotic syndrome
• Nephrosis
• Nuclear factor kappa B
• Puromycin aminonucleoside

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 kappa B (NF-kappa B) of podocyte is strongly associated with the development of proteinuria in MCNS. Dehydroxymethylepoxyquinomicin (DHMEQ) is a novel NF-kappa B inhibitor that potently inhibits DNA-binding activity of NF-kappa B, 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 glomeruli indicated that DHMEQ can inhibit the podocyte foot process effacement via blocking the translocation of podocyte NF-kappa B from cytoplasm to nucleus. Conclusions: These results suggest that DHMEQ can be a potential therapeutic agent for MCNS.

• 出版日期2013