Mizoribine Suppresses Proliferation of Rat Glomerular Epithelial Cells in Culture and Inhibits Increase of Monocyte Chemoattractant Protein-1 and Macrophage Inflammatory Protein-2 Stimulated by Thrombin

Yamabe, Hideaki; Shimada, Michiko; Murakami, Reiichi; Fujita, Takeshi; Shimaya, Yuko; Nakamura, Norio

doi:10.1248/bpb.35.705

Cited by 3 publications

(6 citation statements)

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“…Recently, Yamabe et al . reported that MZR inhibits increases in the MCP‐1 mRNA and protein in dose‐dependently in the range of 1–100 μg/mL in thrombin‐treated rat glomerular epithelial cells . These experimental observations suggest that MZR, besides its immunosuppressive effect, directly inhibits monocyte chemmoattractant, MCP‐1 in human as well as rat inflamed glomerular cells .…”

Section: Discussionmentioning

confidence: 72%

“…reported that MZR inhibits increases in the MCP‐1 mRNA and protein in dose‐dependently in the range of 1–100 μg/mL in thrombin‐treated rat glomerular epithelial cells . These experimental observations suggest that MZR, besides its immunosuppressive effect, directly inhibits monocyte chemmoattractant, MCP‐1 in human as well as rat inflamed glomerular cells . As anti‐inflammatory steroids and an immunosuppressant, Tac are used for the treatment of patients with lupus nephritis, we examined the inhibitory effect of dexamethasone and Tac on the induction of MCP‐1 and IL‐8.…”

Section: Discussionmentioning

confidence: 88%

“…To the best of our knowledge, there is no report describing a beneficial direct effect of MZR on the inflamed ‘human’ MCs. Regarding the concentration, since MZR excreted unchanged into urine, high concentration of 100 μg/mL of the drug at residual glomerular cells is not so irrelevant in a clinical setting . Since Uemura et al .…”

Section: Discussionmentioning

confidence: 99%

“…Since most of the oral dose of MZR is excreted unchanged in urine, the drug is thought to expose directly to residual renal cells. Thus, it is important to examine the direct effects of MZR against inflamed residual renal cells …”

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confidence: 99%

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Mizoribine selectively attenuates monocyte chemoattractant protein‐1 production in cultured human glomerular mesangial cell: A possible benefit of its use in the treatment of lupus nephritis

et al. 2013

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Mizoribine selectively attenuates monocyte chemoattractant protein‐1 production in cultured human glomerular mesangial cell: A possible benefit of its use in the treatment of lupus nephritis

et al. 2013

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“…Recent studies have demonstrated that MZR suppresses infiltration of macrophages, which play an important role in the development of interstitial fibrosis and obstructive nephropathy in rats and proliferation of rat glomerular epithelial cells (4,5). Recent reports stated that concomitant administration of MZR significantly improved CsA-induced interstitial fibrosis and macrophage infiltration in CsA-treated rats.…”

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confidence: 99%

Synergistic protective effects of mizoribine and angiotensin II receptor blockade on cyclosporine A nephropathy in rats

et al. 2013

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BACKGROUND:Chronic cyclosporine A (CsA) nephrotoxicity is manifested by renal dysfunction, progressive histopathological kidney lesions characterized by afferent arteriolopathy, and tubulointerstitial fibrosis. In addition to the direct toxic effect of CsA, many other etiological factors such as angiotensin II, transforming growth factor (TGF)-β, and macrophage infiltration are involved in this pathogenesis. This study investigated the hypothesis that concomitant administration of mizoribine (MZR) and angiotensin II receptor blockade (ARB) may prevent CsA nephrotoxicity in rats. MethODs: Sprague-Dawley male rats were divided into the following seven groups: group 1, treated with CsA; group 2, treated with CsA + MZR; group 3, treated with CsA + valsartan (Val); group 4, treated with CsA + MZR + Val; group 5, treated with MZR; group 6, treated with Val; and group 7, controls (n = 5 each). Renal histopathology and the effect of CsA-induced nephrotoxicity on inflammatory mediators were evaluated. ResUlts:Results of this study demonstrated that ARB administration significantly decreased arteriolopathy and that in comparison with monotherapy, concomitant administration of MZR and ARB further decreased arteriolopathy, fibrosis, macrophage infiltration, and TGF-β1 mRNA expression associated with CsA nephrotoxicity. CONClUsiON: These findings indicate that MZR and ARB combination treatment provides synergistic protective effects against chronic CsA nephrotoxicity. C yclosporine A (CsA), a fungal cyclic polypeptide, is an immunosuppressant widely used in cases of organ transplantation and autoimmune diseases. CsA administration has been extended to the treatment of nephrotic syndrome in children, particularly in those with steroid dependency and resistant nephrotic syndrome due to steroid toxicity (1). However, the therapeutic benefits of CsA are often limited by chronic nephrotoxicity developing from long-term use of this drug. Chronic CsA nephrotoxicity is manifested by renal dysfunction and progressive histopathological kidney lesions characterized by afferent arteriolopathy, tubular vacuolization, tubular atrophy, and interstitial fibrosis (2).Mizoribine (MZR) is a purine nucleotide analog isolated from Eupenicillium brefeldianum (3) and has been clinically used as an immunosuppressant following renal transplantation and for lupus nephritis and for nephrotic syndrome. Recent studies have demonstrated that MZR suppresses infiltration of macrophages, which play an important role in the development of interstitial fibrosis and obstructive nephropathy in rats and proliferation of rat glomerular epithelial cells (4,5). Recent reports stated that concomitant administration of MZR significantly improved CsA-induced interstitial fibrosis and macrophage infiltration in CsA-treated rats. However, no decrease in arteriolopathy or expression of transforming growth factor (TGF)-β1 was observed after additional MZR administration in a model of CsA nephropathy (6).On the other hand, activation of the renin-angiotensin-aldosterone sy...

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Mizoribine in the treatment of pediatric-onset glomerular disease

2015

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Mizoribine Suppresses Proliferation of Rat Glomerular Epithelial Cells in Culture and Inhibits Increase of Monocyte Chemoattractant Protein-1 and Macrophage Inflammatory Protein-2 Stimulated by Thrombin

Cited by 3 publications

References 28 publications

Mizoribine selectively attenuates monocyte chemoattractant protein‐1 production in cultured human glomerular mesangial cell: A possible benefit of its use in the treatment of lupus nephritis

Mizoribine selectively attenuates monocyte chemoattractant protein‐1 production in cultured human glomerular mesangial cell: A possible benefit of its use in the treatment of lupus nephritis

Synergistic protective effects of mizoribine and angiotensin II receptor blockade on cyclosporine A nephropathy in rats

Mizoribine in the treatment of pediatric-onset glomerular disease

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