MP74-15 A NOVEL NF-?B INHIBITOR DEHYDROXYMETHYLEPOXYQUINOMICIN PREVENTS ACUTE REJECTION OF KIDNEY ALLOGRAFTS IN A RAT MODEL

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III1 Apr 2017MP74-15 A NOVEL NF-?B INHIBITOR DEHYDROXYMETHYLEPOXYQUINOMICIN PREVENTS ACUTE REJECTION OF KIDNEY ALLOGRAFTS IN A RAT MODEL Kazunobu Shinoda, Shinya Morita, Kazuhiro Matsumoto, Takeo Kosaka, Ryuichi Mizuno, Toshiaki Shinojima, Eiji Kikkuchi, Hiroshi Asanuma, Akira Miyajima, Kazuo Umezawa, and Mototsugu Oya Kazunobu ShinodaKazunobu Shinoda More articles by this author , Shinya MoritaShinya Morita More articles by this author , Kazuhiro MatsumotoKazuhiro Matsumoto More articles by this author , Takeo KosakaTakeo Kosaka More articles by this author , Ryuichi MizunoRyuichi Mizuno More articles by this author , Toshiaki ShinojimaToshiaki Shinojima More articles by this author , Eiji KikkuchiEiji Kikkuchi More articles by this author , Hiroshi AsanumaHiroshi Asanuma More articles by this author , Akira MiyajimaAkira Miyajima More articles by this author , Kazuo UmezawaKazuo Umezawa More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2183AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Clinical regimens of immunosuppression involve different types of agents because the targets of each drug are the halfway points of signaling pathways leading to expression of various essential proteins in immune cells activation. Nuclear factor (NF)-?B is one of key transcriptional factors and is located in the down stream of several signaling pathways activated in immune responses. Therefore pharmacological modulation of NF-?B activities may be of great use for the treatment of allograft rejection. In this study, we investigated for an immunosuppressive effect of a novel NF-?B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), using a rat kidney transplant model between a highly immune reactive combination. METHODS We performed kidney allograft transplant in a rat acute rejection model (WKAH to LEWIS rats, age 6-8 weeks). Rats were randomly assigned into 3 groups (A: control group, not administrated DHMEQ, B: administration of 12 mg/kg DHMEQ, C: administration of 20 mg/kg DHMEQ). DHMEQ was administrated i.p. once daily for consecutive 10 days. Urine and blood samples were collected every each day. The date of anuria was determined as the date of rejection. Transplanted kidney allografts were also explanted on the 4th postoperative day and the infiltration rates of T cells and monocytes were investigated by immunohistochemistry. RESULTS DHMEQ significantly prolonged kidney allograft survival. (7.2 ± 1.4 post-transplant days, 13.5 ± 3.4 post-transplant days, 19.4 ± 4.5 post-transplant days, for a control (group A), 12 mg/kg DHMEQ (group B), 20 mg/kg DHMEQ (group C), respectively). There was a reduction of T cell and macrophage infiltration to DHMEQ-treated kidney allografts compared to control allografts. The production of pro-inflammatory cytokines including IL-6, IL-12 p70, TNF-a in the recipients treated with DHMEQ was significantly decreased compared to that in the control group. No remarkable side effects were observed during the experiments. CONCLUSIONS DHMEQ is remarkably effective in preventing kidney allograft rejection. DHMEQ can be administrated safely and could be involved in a new immunosuppressive strategy, which allows reducing the dose of current immunosuppressive agents. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1001 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Kazunobu Shinoda More articles by this author Shinya Morita More articles by this author Kazuhiro Matsumoto More articles by this author Takeo Kosaka More articles by this author Ryuichi Mizuno More articles by this author Toshiaki Shinojima More articles by this author Eiji Kikkuchi More articles by this author Hiroshi Asanuma More articles by this author Akira Miyajima More articles by this author Kazuo Umezawa More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...