Disease relevance of Deskar

• Pirfenidone in idiopathic pulmonary fibrosis [1].
• A pilot study in patients with established advanced liver fibrosis using pirfenidone [2].
• Because leiomyomas are characterized also by increased cell proliferation and tissue fibrosis, we examined the effects of pirfenidone on cell proliferation and collagen expression in cultured myometrial and leiomyoma smooth muscle cells [3].
• Pirfenidone: a novel pharmacological agent that inhibits leiomyoma cell proliferation and collagen production [3].
• Overall, these studies demonstrated the potential utility of pirfenidone as a therapeutic against septic shock and the biological effects of SEB [4].

High impact information on Deskar

• Serum-stimulated increases in DNA synthesis and cell proliferation by myometrial and leiomyoma cells were significantly inhibited in a dose-dependent manner by pirfenidone [3].
• Administration of pirfenidone after sensitization but during the period of ovalbumin challenge significantly prevented the development of airway hyperresponsiveness and prevented eosinophil and lymphocyte accumulation in the airways [5].
• Pirfenidone reduced the expression of transforming growth factor-beta1, the development of goblet cell hyperplasia and subepithelial collagenization, and the increases in contractile elements in the lung [5].
• In addition, the antifibrotic molecule pirfenidone (PFD) was shown to ameliorate fibrosis in this model [6].
• Studies were performed to investigate whether pirfenidone directly influences iNOS induction in hepatocytes [7].

Chemical compound and disease context of Deskar

• The data obtained in this study provide evidence of the benefical effects of pirfenidone in the hamster model of bleomycin-induced pulmonary fibrosis both at the functional and biochemical level [8].
• Bleomycin-induced fibrosis and the effectiveness of pirfenidone treatment were assessed by measuring pulmonary functions (Cqst, TLC, VC, IC, FRC, RV) and the level of hydroxyproline in whole lung homogenates [8].
• Reversal of cardiac and renal fibrosis by pirfenidone and spironolactone in streptozotocin-diabetic rats [9].
• Modulation of airway remodeling-associated mediators by the antifibrotic compound, pirfenidone, and the matrix metalloproteinase inhibitor, batimastat, during acute lung injury in mice [10].
• BACKGROUND: The antifibrotic substance pirfenidone and the angiotensin II type I receptor antagonist candesartan cilexetil, given alone and in combination, were tested in rats with chronic anti-glomerular basement membrane glomerulonephritis (anti-GBM GN) [11].

Biological context of Deskar

• CONCLUSIONS: Results indicate that pirfenidone inhibits the induction of iNOS gene expression at a step of NF-kappaB DNA binding, but not its nuclear translocation, partly through the inhibition of IL-1 receptor induction in hepatocytes [7].
• Finally, pirfenidone inhibited the activation of Akt and up-regulation of IL-1 receptor stimulated by IL-1beta [7].
• RESULTS: Pirfenidone significantly inhibited PDGF-induced HSC proliferation, starting at a concentration of 1 microM, with a maximal effect at 1000 microM, without affecting HSC viability and without inducing apoptosis [12].
• Consistent with this observation, transfection experiments revealed that pirfenidone decreased transcriptional activation of iNOS gene promoter [7].
• 2. In control rats, the elimination half-life of pirfenidone following a single intravenous dose of 200 mg kg(-1) was 37 min while oral bioavailability at this dose was 25.7% [13].

Anatomical context of Deskar

• Pirfenidone also inhibits production of tumor necrosis factor alpha (TNF-alpha) from macrophages incubated with endotoxin and protects mice against endotoxin shock [4].
• In vitro experiments with human peripheral blood lymphocytes revealed that pirfenidone reduced SEB-induced cytokine levels 50 to 80% and inhibited 95% of SEB-induced T-cell proliferation [4].
• The aim of this study was to evaluate the effect of Pirfenidone in the reversion or prevention of cirrhosis experimentally induced in rats by chronic administration of CCl(4) and bile-duct ligation (BDL) [14].
• 4. Collagen deposition was significantly increased in the interstitium after 2 weeks and further increased with scarring of the left ventricle after 4 weeks; pirfenidone and amiloride reversed the increases and prevented further increases [13].
• These data indicate a novel mechanism of action for pirfenidone to reduce the activation of synovial fibroblasts [15].

Associations of Deskar with other chemical compounds

• RESULTS: High levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase decreased significantly (P<0.001) in animals treated with Pirfenidone (n=11) with regard to saline-administrated animals (n=9) [14].
• This project has determined whether pirfenidone, a new antifibrotic compound, and spironolactone, an aldosterone antagonist, reverse both deposition of the major extracellular matrix proteins, collagen and fibronectin, and functional changes in the streptozotocin(STZ)-diabetic rat [9].
• A single oral administration of pirfenidone 1, 2, 3, 4 and 5 h post lipopolysaccharide/D-galactosamine challenge provided protection against lethal shock in a time-dependent manner [16].
• Matrix metalloproteinase-2 expression was decreased by cyclosporine; all doses of pirfenidone significantly reversed this effect [17].
• Other laboratories have evaluated pirfenidone, halofuginone, heparin, and interferon-alpha (IFN-alpha) [18].

Gene context of Deskar

• A novel anti-fibrotic agent pirfenidone suppresses tumor necrosis factor-alpha at the translational level [19].
• A comparison of factors associated with collagen metabolism in different skeletal muscles from dystrophic (mdx) mice: Impact of pirfenidone [20].
• The in vivo model also showed that pirfenidone suppressed the cytokine production by a translational mechanism, though interleukin-10 transcription was activated by pirfenidone [19].
• Pretreatment with pirfenidone reduced neutrophil recruitment, TNF-alpha and TGF-beta levels, and MMP-9 secretion [10].
• Pirfenidone at a dosage of 50 mg x kg(-1) x d(-1) inhibited protein expression of TGF-beta1 and TIMP-1 in lung tissue in the early phase (0.79 and 0.75 times of control group), but had no effect on expression of MMP-13 [21].

Analytical, diagnostic and therapeutic context of Deskar

• In a prespecified subset of patients who maintained a SpO2 greater than 80% during a 6-minute exercise test at baseline, the lowest SpO2 improved during a 6-minute exercise test in the pirfenidone group at 6 and 9 months (p = 0.0069 and 0.0305, respectively) [22].
• Using this murine heterotopic tracheal allograft model, we evaluated the effect of pirfenidone, a novel antifibrotic agent, on the development of OAD [23].
• Forty percent (2/5) of mice receiving a continuous regimen of pirfenidone beginning on day 5 after transplantation had no evidence of OAD at 28 days [23].
• Pirfenidone prevents endotoxin-induced liver injury after partial hepatectomy in rats [24].
• Treatment with pirfenidone significantly reduced transforming growth factor-beta1 and platelet-derived growth factor levels in bronchoalveolar lavage fluid [5].

References