The effect of photosensitive dye Platonin on juvenile rheumatoid arthritis

Motoyoshi, Fumiaki; Kondo, Naomi; Ono, Hiromasa; Orii, Tadao

doi:10.1007/bf02171687

Cited by 23 publications

(18 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, it is well known that PDGF transmits its signal into the intracellular space through the activation of AKT and mitogen-activated protein kinases (MAPKs) [8] . Platonin (4,4',4"-thrimethyl-3,3',3"-triheptyl-7-[2"-thiazolyl]-2,2'-trimethinethiazolocyanine-3-3"-diiodide) (Figure 1), a cyanine photosensitizing dye, is an immunomo dulator [9,10] currently in use as an effective medicine for rheumatoid arthritis [10,11] . Administration of platonin is known to inhibit the up-regulation of inflammatory molecules, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) in endotoxin-activated macrophages [12,13] .…”

Section: Introductionmentioning

confidence: 99%

Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling

Chang

Uen²,

Chen

et al. 2011

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: To examine the inhibitory actions of the immunoregulator platonin against proliferation of rat vascular smooth muscle cells (VSMCs). Methods: VSMCs were prepared from the thoracic aortas of male Wistar rats. Cell proliferation was examined using MTT assays. Cell cycles were analyzed using flow cytometry. c-Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, AKT, and c-Jun phosphorylation or p27 expression were detected using immunoblotting. Results: Pretreatment with platonin (1-5 μmol/L) significantly suppressed VSMC proliferation stimulated by PDGF-BB (10 ng/mL) or 10% fetal bovine serum (FBS), and arrested cell cycle progression in the S and G 2 /M phases. The same concentrations of platonin significantly inhibited the phosphorylation of JNK1/2 but not ERK1/2 or AKT in VSMCs stimulated by PDGF-BB. Furthermore, platonin also attenuated c-Jun phosphorylation and markedly reversed the down-regulation of p27 expression after PDGF-BB stimulation. Conclusion: Platonin inhibited VSMC proliferation, possibly via inhibiting phosphorylation of JNK1/2 and c-Jun, and reversal of p27 down-regulation, thereby leading to cell cycle arrest at the S and G 2 /M phases. Thus, platonin may represent a novel approach for lowering the risk of abnormal VSMC proliferation and related vascular diseases.

show abstract

Section: Introductionmentioning

confidence: 99%

Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling

Chang

Uen²,

Chen

et al. 2011

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…Platonin, a cyanine photosensitizing dye, is a potent macrophage-activating agent (3,4) and an immunomodulator (5,6). It has been prescribed for rheumatoid arthritis (5,6).…”

mentioning

confidence: 99%

“…It has been prescribed for rheumatoid arthritis (5,6). Recently, we have provided evidence to demonstrate that platonin has beneficial effects on ameliorating endotoxemia in rat models (7).…”

mentioning

confidence: 99%

Platonin, a Cyanine Photosensitizing Dye, Inhibits Pyrogen Release and Results in Antipyresis

et al. 2003

View full text Add to dashboard Cite

Abstract. Intravenous injection of the supernatant fluids from human peripheral blood mononuclear cells (PBMC) incubated with lipopolysaccharide (LPS) caused fever in rabbits. The fever was in parallel with the levels of either interleukin-1b (IL-1b), IL-6, or tumor necrosis factor-a (TNF-a ) in supernatant fluids. When incubating the platonin with the LPS-human PBMC, both the levels of IL-1b, IL-6, or TNF-a in supernatant fluids and the pyrogenicity of supernatant fluids were significantly suppressed. The febrile response to supernatant fluids from the LPSstimulated PBMC was attenuated almost completely by adding anti-IL-1b, but not anti-IL-6 or anti-TNF-a , monoclonal antibody to supernatant fluids. In addition, both the fever and the increased levels of either IL-1b, IL-6, or TNF-a in rabbit serum following an intravenous administration of LPS were significantly attenuated by pretreatment with an intravenous dose of platonin. Furthermore, the fever induced by intravenous injection of IL-1b was reduced by pretreatment of rabbits with intravenous injection of platonin. The data indicate that platonin inhibits production of pyrogenic cytokines (in particular, IL-1b) from PBMC and results in antipyresis.

show abstract

“…[10][11][12][13] It was reported that platonin, a kind of cyanine dye, suppressed acute endotoxemia in rats by inhibiting inflammatory cytokine release from lipopolysaccharide (LPS)-stimulated lymphocytes.…”

mentioning

confidence: 99%

“…[6][7][8][9] Some of those dyes have been used as immunomodulators to treat allergy and rheumatoid arthritis, and to promote wound-healing. [10][11][12][13] It was reported that platonin, a kind of cyanine dye, suppressed acute endotoxemia in rats by inhibiting inflammatory cytokine release from lipopolysaccharide (LPS)-stimulated lymphocytes. 14,15) Recent studies suggested that neutrophil infiltration and release of inflammatory cytokines (i.e., interleukin (IL)-1b, IL-6, IL-17, IL-23, and tumor necrosis factor-a) participate in a secondary mechanism of brain injury following ischemia and reperfusion.…”

mentioning

confidence: 99%

Cyanine Dyes Attenuate Cerebral Ischemia and Reperfusion Injury in Rats

Koya‐Miyata

Ohta

Akita

et al. 2010

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Ischemic stroke is a leading cause of death and long-lasting disability. However, therapeutic options for acute ischemic stroke remain very limited.1) Ischemic stroke triggers a cascade of pathophysiological events including excitotoxicity, ionic imbalance, oxidative stress, and apoptosis-like cell death ending in destructive neurodegeneration.2-4) The cumulative evidence suggests involvement of reactive oxygen species (ROS) in the pathogenesis of ischemic injury.5) Several components of ROS including superoxides ( · O 2 Ϫ ), hydroxyl radicals ( · OH), and hydrogen peroxide (H 2 O 2 ) are generated by post-ischemia/reperfusion injury. They are known to induce DNA damage, lipid peroxidation, disruption of blood brain-barrier (BBB), and microglial activation in the ischemic tissue. The rat middle cerebral artery occlusion (MCAO) model mimics the pathophysiological consequences induced by ischemic stroke in humans and thus has been frequently employed.Cyanine photosensitizing dyes have been shown to have various biological activities, such as antimicrobial, antioxidant, macrophage activation, and oxidative phosphorylation uncoupling activities.6-9) Some of those dyes have been used as immunomodulators to treat allergy and rheumatoid arthritis, and to promote wound-healing. [10][11][12][13] It was reported that platonin, a kind of cyanine dye, suppressed acute endotoxemia in rats by inhibiting inflammatory cytokine release from lipopolysaccharide (LPS)-stimulated lymphocytes.14,15) Recent studies suggested that neutrophil infiltration and release of inflammatory cytokines (i.e., interleukin (IL)-1b, IL-6, IL-17, IL-23, and tumor necrosis factor-a) participate in a secondary mechanism of brain injury following ischemia and reperfusion. [16][17][18] Because there is substantial evidence showing that immune responses play crucial roles in mediating neuronal damage in the animal model of stroke, 16) it is reasonable to expect that cyanine dyes with anti-inflammatory properties could protect against neuroinflammatory events. To our knowledge, little is not known whether these dyes are pharmacologically active against ischemia-induced brain injury or neurodegenerative disorders. To explore this potential of cyanine dyes, it would be of interest to examine their effects in the MCAO model, an animal model of ischemic stroke. Prior to the in vivo evaluation, we screened more than 250 cyanine dyes for their neurotrophin-like activity (such as potentiation of neurite outgrowth in neural cells) and found that NK-4 (Fig. 1A), NK-150 (Fig. 1B), and some other related compounds showed remarkable neurite outgrowth-promoting activity in PC12 neural cells. NK-4 and NK-150 are thought to be safe compounds since they showed no acute toxicity when orally-administrated to mice at a dose of 2000 mg/kg (our unpublished observation). In the present report, we further examined NK-4 and NK-150 for their ability to promote nerve growth factor (NGF)-primed neurite outgrowth and for free radical scavenging activity in vitro. We also examined the...

show abstract

The effect of photosensitive dye Platonin on juvenile rheumatoid arthritis

Cited by 23 publications

References 4 publications

Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling

Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling

Platonin, a Cyanine Photosensitizing Dye, Inhibits Pyrogen Release and Results in Antipyresis

Cyanine Dyes Attenuate Cerebral Ischemia and Reperfusion Injury in Rats

Contact Info

Product

Resources

About