Disease relevance of tranilast

• Treatment with tranilast, a mast cell-stabilizing agent, also prevented the evolution from compensated hypertrophy to heart failure [1].
• Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by induction of p21(waf1/cip1/sdi1) and p53 [2].
• Therefore, the effects of tranilast on kidney fibrosis and dysfunction were examined in the subtotal nephrectomy model of progressive renal injury [3].
• In the context of a recent pilot study in humans, the findings of the present report suggest that tranilast may provide a novel strategy for the treatment of progressive kidney disease characterized by fibrotic scarring [3].
• Long-term prospective pilot study with tranilast for the prevention of stricture progression in patients with Crohn's disease [4].

Psychiatry related information on tranilast

• Twenty patients fulfilled the criteria, of whom 10 were selected at random and commenced on tranilast [100 mg, 3 times daily; T(+) group] [5].

High impact information on tranilast

• Flow cytometry analysis of isolated human and rabbit peripheral blood mononuclear cells showed that an increase in expression both of MHC class II antigen on monocytes by incubation with interferon-gamma and of IL-2 receptor on T cells by IL-2 was suppressed by the combined incubation with tranilast [6].
• CONCLUSIONS: The results indicate that tranilast suppresses atherosclerotic development partly through direct inhibition of immunological activation of monocytes/macrophages and T cells in the atheromatous plaque [6].
• Tranilast [N-(3,4-dimethoxycinnamoyl) anthranillic acid] inhibits release of cytokines and chemical mediators from various cells, including macrophages, leading to suppression of inflammatory and immunological responses [6].
• Immunohistochemical staining demonstrated that, in tranilast-treated rats, p21 was already present in the neointima at day 7 and strongly expressed throughout the neointima at day 14 [2].
• Tranilast suppressed their activities by >80% without reduction of CDK2/cyclin E and CDK4/cyclin D1 protein levels [2].

Chemical compound and disease context of tranilast

• These findings indicate that the combination of tranilast and perindopril was superior to single-agent treatment on kidney structure and function in the remnant kidney model, and suggests the potential for such dual therapy in kidney disease that continues to progress despite blockade of the renin-angiotensin system [7].
• Determination of the cardiac hydroxyproline content similarly revealed a significant reduction in cardiac fibrosis by tranilast (2K1C: 4.92 +/- 0.48 mg/mg; 2K1C + tranilast: 3.97 +/- 0.46 mg/mg; P < 0.05) [8].
• When compared with single-agent treatment, the combination of tranilast and perindopril provided additional, incremental improvements in creatinine clearance, proteinuria, and glomerulosclerosis, and a reduction in nuclear phsopho-Smad2 beyond single-agent treatment [7].
• The present study was performed to investigate the effects of the antiallergic drug tranilast on the development of diabetic nephropathy in streptozotocin (50 mg/kg)-induced diabetic spontaneously hypertensive rats (SHR) [9].
• Experimental studies have shown that N(3',4'-dimethoxycinnamoyl) anthranilic acid (Tranilast) inhibits reaginic antibody-mediated hypersensitivity reactions, and it has been demonstrated to be an effective drug for patients with bronchial asthma [10].

Biological context of tranilast

• Tranilast (100 mg x kg(-1) x d(-1) p.o.) significantly (P<0.05) reduced smooth muscle cell proliferation in the neointima and media 7 days after injury and neointimal formation 21 days after injury in treated mice compared with vehicle-treated mice [11].
• Tranilast inhibited the proliferation of cultured leiomyoma cells in a dose-dependent manner without any cytotoxic effect or induction of apoptosis [12].
• In addition, PDGF-induced calcium influx in the late G1 phase, as assessed by measuring the initial uptake of 45Ca, was inhibited by tranilast in a concentration-dependent manner [13].
• Therefore, in therapeutically relevant concentrations (50 microg/ml), tranilast inhibits NF-kappaB-dependent transcriptional activation by interfering with the NF-kappaB/CBP association [14].
• Expression of the transcriptional coactivator cAMP response element binding protein binding protein (CBP) was inhibited by tranilast, resulting in a loss of interaction between NF-kappaB and CBP [14].

Anatomical context of tranilast

• To elucidate this mechanism, we studied the effect of tranilast on the proliferation of vascular smooth muscle cells (SMCs) in vitro and in vivo [2].
• CONCLUSIONS: In pig coronary arteries, tranilast was associated with a reduction in neointima formation and adventitial reaction after balloon injury [15].
• Tranilast is known to suppress fibrosis or to work as a mast cell stabilizer and is reported to inhibit proliferation of vascular smooth muscle cells [12].
• Tranilast inhibits cytokine-induced nuclear factor kappaB activation in vascular endothelial cells [14].
• Cultured human umbilical vein endothelial cells were preincubated with 12.5 to 100 microg/ml tranilast [14].

Associations of tranilast with other chemical compounds

• METHODS: Sprague-Dawley rats treated with DOCA combined with the addition of 1% NaCl and 0.2% KCl in the drinking water after left nephrectomy were given tranilast (100 mg/kg per day, n = 15) or vehicle (n = 15) for up to 4 weeks [16].
• Tranilast antagonizes angiotensin II and inhibits its biological effects in vascular smooth muscle cells [17].
• Histamine caused phasic and tonic increases in [Ca2+]i, and high K+ caused a tonic increase in [Ca2+]i of smooth muscle, both of which were significantly suppressed in the presence of tranilast [18].
• Furthermore, Tranilast prevented the PGD2 generation from intact mast cells stimulated by the calcium ionophore A23187 [19].
• Concentrations of less than 200 microM of anti-allergic drugs without H1-receptor antagonism, tranilast, repirinast and ibudilast, did not inhibit neutrophil NADPH oxidase in whole-cell and cell-free systems [20].

Gene context of tranilast

• Tranilast inhibits the proliferation of uterine leiomyoma cells in vitro through G1 arrest associated with the induction of p21(waf1) and p53 [12].
• These results suggest that tranilast arrests the proliferation of uterine leiomyoma cells at the G0/G1 phase, through the suppression of CDK2 activity via an induction of p21(waf1) and p53 [12].
• Further, tranilast reduces the release of TGF-beta1 and TGF-beta2 by glioma cells and inhibits migration, chemotactic responses and invasiveness [21].
• Tranilast reduced CTGF mRNA and phosphorylation of Smad2, which were induced by TGF-beta1 in PTCs and CFs [22].
• Effect of tranilast on matrix metalloproteinase production from neutrophils in-vitro [23].

Analytical, diagnostic and therapeutic context of tranilast

• BACKGROUND: Tranilast, which has antikeloid and antiallergic properties and therefore may modulate the fibrotic and inflammatory tissue responses to angioplasty and stenting, has been shown to inhibit angiographic restenosis in small clinical trials [15].
• Inhibition of neointima formation by tranilast in pig coronary arteries after balloon angioplasty and stent implantation [15].
• METHODS: Following initial pharmacokinetic studies in two pigs to determine desirable plasma levels of orally administered tranilast, 36 crossbred juvenile pigs were randomized to placebo or tranilast before undergoing balloon angioplasty in both the left anterior descending and left circumflex plus stent implantation in the right coronary artery [15].
• After a recession of the superior rectus muscle (SRM), a PTFE/PLGA laminate containing tranilast, PTFE alone, or balanced salt solution was applied beneath and over the SRM in the PTFE/PLGA-tranilast group (group P-T), the PTFE group (group P), and the control group, respectively [24].
• OBJECTIVE: Recent studies suggest that tranilast inhibits a variety of agents implicated in neointimal growth and restenosis in experimental animal models and humans [25].

References