Date: Tuesday, June 14, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
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.
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).
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).
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 November 26, 2020.
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