Novel Nuclear Factor-κB Activation Inhibitor, Dehydroxymethylepoxyquinomicin, Prevents the Development of Chronic Cyclosporine Nephropathy in Rats.
1Urology, Keio University School of Medicine, Tokyo, Japan
2Urology, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Chiba, Japan
3Nephrology, Tokyo Medical University, Tokyo, Japan
4Molecular Target Medicine Screening, Aichi Medical University, Nagakute, Aichi, Japan.
Meeting: 2016 American Transplant Congress
Abstract number: D82
Keywords: Calcineurin, Nephropathy
Session Information
Date: Tuesday, June 14, 2016
Session Name: Poster Session D: Chimerism/Stem Cells, Cellular/Islet Transplantation, Innate Immunity, Chronic Rejection
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Purpose:
The nephrotoxicity of the calcineurin inhibitors including cyclosporine is a major problem in the kidney transplantation. We investigated the effect of a novel nuclear factor-κB (NF-κB) activation inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on chronic cyclosporine nephropathy using a rat model.
Methods:
We performed 5/6 nephrectomy in Sprague-Dawley rats bred with low sodium diet. These rats were treated with the intraperitoneal administration of relatively high doses of cyclosporine (15mg/kg daily) (cyclosporine group, N=5) or treated with saline (control group, N=5). The other group was additionally treated with the intraperitoneal administration of DHMEQ (8mg/kg daily) (DHMEQ treatment group, N=3). Urine samples were collected on day 28 for 24 hours. The blood was collected and the kidneys were harvested on day 29. The sections of the kidney samples with Masson-trichrome staining were scanned and the area of interstitial fibrosis was measured by using a software (DIFINIENS;Tissue Studio Dual). The proteins in the cytoplasm and the nucleus were separately collected from the samples to measure the relative increase in NF-κB p65 translocation into the nucleususing an enzyme-linked immunosorbent assay (ELISA).
Results:
The creatinine clearance levels in the DHMEQ treatment group were significantly higher in comparison with the cyclosporine group (0.87 ±0.02 ml/min vs. 0.58 ±0.05 ml/min, respectively). The Area measurements demonstrated that the interstitial fibrosis in the renal cortex less developed in the DHMEQ treatment group than those in the cyclosporine group (10.2 ± 0.9 % vs. 20.2 ± 0.1 %, respectively). The ELISA assays showed that the relative ratioof nuclear to cytoplasmic p65 in kidney samples in the cyclosporine group was up-regulated in comparison with that in the control group (196 ± 4 vs. 100 ± 21, respectively), while that in the DHMEQ treatment group was down-regulated in comparison with the cyclosporine group ( 147 ± 8 vs. 196 ± 4, respectively).
Conclusions:
Treatment with DHMEQ prevents the development of renal interstitial fibrosis due to chronic cyclosporine nephropathy and maintains the renal function.
CITATION INFORMATION: Morita S, Shinoda K, Tamaki S, Kono H, Kanno Y, Umezawa K, Nakagawa K, Oya M. Novel Nuclear Factor-κB Activation Inhibitor, Dehydroxymethylepoxyquinomicin, Prevents the Development of Chronic Cyclosporine Nephropathy in Rats. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Morita S, Shinoda K, Tamaki S, Kono H, Kanno Y, Umezawa K, Nakagawa K, Oya M. Novel Nuclear Factor-κB Activation Inhibitor, Dehydroxymethylepoxyquinomicin, Prevents the Development of Chronic Cyclosporine Nephropathy in Rats. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/novel-nuclear-factor-b-activation-inhibitor-dehydroxymethylepoxyquinomicin-prevents-the-development-of-chronic-cyclosporine-nephropathy-in-rats/. Accessed January 25, 2021.« Back to 2016 American Transplant Congress