A novel nuclear factor κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates puromycin aminonucleoside-induced nephrosis in mice.

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.

• Authors: Tomohiko Shimo, Yasushi Adachi, Sohsaku Yamanouchi, Shoji Tsuji, Takahisa Kimata, Kazuo Umezawa, Mitsuhiko Okigaki, Junji Takaya, Susumu Ikehara, Kazunari Kaneko
• Journal: American journal of nephrology (Am J Nephrol) Vol. 37 Issue 4 Pg. 302-9 ( 2013) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 23548793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 S. Karger AG, Basel.

Chemical References

• Benzamides
• Blood Proteins
• Cyclohexanones
• Interleukin-6
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• NF-kappa B
• NPHS2 protein
• Serum Albumin
• dehydroxymethylepoxyquinomicin
• nephrin
• Puromycin Aminonucleoside
• Cholesterol
• Glycerolphosphate Dehydrogenase
• Adenosine Deaminase

Topics

• Adenosine Deaminase (metabolism)
• Albuminuria (urine)
• Animals
• Benzamides (administration & dosage)
• Blood Proteins (analysis)
• Cholesterol (blood)
• Cyclohexanones (administration & dosage)
• Glycerolphosphate Dehydrogenase (metabolism)
• Interleukin-6 (blood)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Kidney (pathology)
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Mice, Inbred C57BL
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nephrosis (chemically induced, metabolism, pathology, prevention & control)
• Proteinuria (urine)
• Puromycin Aminonucleoside (toxicity)
• Rats
• Serum Albumin (analysis)