Ibudilast, an anti-allergic and cerebral vasodilator, modulates superoxide production in human neutrophils

Niwa, Masayuki; Kohno, Katsuyuki; Al‐Essa, Luay Y.; Kobayashi, Masashi; Nozaki, Masakatsu; Tsurumi, Kaito

doi:10.1016/0024-3205(94)00420-w

Cited by 20 publications

(4 citation statements)

References 17 publications

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“…However, the leukotriene D 4 receptor antagonist LY171883 did not affect the H 2 O 2 ‐induced cell injury. Alternatively, previous studies show that ibudilast is an inhibitor of PDE, and suggest that the effect of ibudilast is mediated partly by cyclic AMP ( Souness et al ., 1994 ; Niwa et al ., 1995 ; Suzumura et al ., 1999 ; Yoshioka et al ., 2000 ). We examined the effects of several PDE inhibitors to clarify the possible involvement of cyclic AMP signalling pathway in the protective effect of ibudilast on the H 2 O 2 ‐induced astrocytic injury.…”

Section: Discussionmentioning

confidence: 99%

Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model

Takuma

Lee

Enomoto

et al. 2001

British J Pharmacology

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1 We examined the eect of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (ibudilast), which has been clinically used for bronchial asthma and cerebrovascular disorders, on cell viability induced in a model of reperfusion injury. 2 Ibudilast at 10 ± 100 mM signi®cantly attenuated the H 2 O 2 -induced decrease in cell viability. 3 Ibudilast inhibited the H 2 O 2 -induced cytochrome c release, caspase-3 activation, DNA ladder formation and nuclear condensation, suggesting its anti-apoptotic eect. 4 Phosphodiesterase inhibitors such as theophylline, pentoxyfylline, vinpocetine, dipyridamole and zaprinast, which increased the guanosine-3',5'-cyclic monophosphate (cyclic GMP) level, and dibutyryl cyclic GMP attenuated the H 2 O 2 -induced injury in astrocytes. 5 Ibudilast increased the cyclic GMP level in astrocytes. 6 The cyclic GMP-dependent protein kinase inhibitor KT5823 blocked the protective eects of ibudilast and dipyridamole on the H 2 O 2 -induced decrease in cell viability, while the cyclic AMPdependent protein kinase inhibitor KT5720, the cyclic AMP antagonist Rp-cyclic AMPS, the mitogen-activated protein/extracellular signal-regulated kinase inhibitor PD98059 and the leukotriene D 4 antagonist LY 171883 did not. 7 KT5823 also blocked the eect of ibudilast on the H 2 O 2 -induced cytochrome c release and caspase-3-like protease activation. 8 These ®ndings suggest that ibudilast prevents the H 2 O 2 -induced delayed apoptosis of astrocytes via a cyclic GMP, but not cyclic AMP, signalling pathway.

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Section: Discussionmentioning

confidence: 99%

Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model

Takuma

Lee

Enomoto

et al. 2001

British J Pharmacology

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“…However, inhibition of the release of inflammatory cytokines, inhibition of leukocyte activation, and inhibition of the expression of cell adhesion molecules have been proposed as likely mechanisms of action of ibudilast (35). Other reported pharmacological actions of ibudilast include inhibition of leukotriene D 4 -induced formation of inositol phosphates (6), antagonism of slow-reacting substance of anaphylaxis (SRS-A) (27), inhibition of tyrosine kinase in neutrophils (23), and inhibition of ATP-sensitive potassium channels (12).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Ibudilast: A Non‐selective PDE Inhibitor with Multiple Actions on Blood Cells and the Vascular Wall

Kishi

Ohta

Kasuya

et al. 2001

Cardiovascular Drug Reviews

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Ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine) is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It is widely used in Japan for improving prognosis and relieving symptoms in patients suffering from ischemic stroke or bronchial asthma. These clinical applications are based on the properties of ibudilast that inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The inhibition of platelet aggregation and vasodilatation by ibudilast may be due to synergistic elevation of intracellular cyclic nucleotides and release of nitric oxide (NO) or prostacyclin from endothelium, rather than direct inhibition of PDE5 or PDE3. Another important property of ibudilast is its antiinflammatory activity possibly associated with potent inhibition of PDE4. Combined with its relaxing effects on bronchial smooth muscle, antiinflammatory actvity of ibudilast could favorably influence pathophysiology of asthma by antagonizing chemical mediators triggering asthmatic attacks. Ibudilast was also reported to significantly attenuate inflammatory cell infiltration in the lumbar spinal cord in an animal model of encephalomyelitis. Future investigations should include effects of ibudilast on inflammatory reactions between endothelium and blood cells, which may initiate the development of atherosclerosis.

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“…Ibudilast inhibited the pharmacological effects and the production of slow reacting substances of anaphylaxis (SRS-A) which were later identified as leukotriene (LT) C 4 , D 4 , E 4 (Ohashi et al, 1986a;Nishino et al, 1983). Ibudilast attenuated the production of proinflammatory mediators and cytokines including superoxide, tumor necrosis factor (TNFa), interferon (IFN)-g and interleukin-6 (Niwa et al, 1995;Mizuno et al, 2004;Feng et al, 2004). In addition, ibudilast selectively increased vertebral and internal carotid blood flow without significantly affecting the systemic blood pressure and cardiac frequency of anesthetized dogs (Kudo et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Preferential inhibition of human phosphodiesterase 4 by ibudilast

et al. 2006

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Ibudilast, an anti-allergic and cerebral vasodilator, modulates superoxide production in human neutrophils

Cited by 20 publications

References 17 publications

Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model

Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model

Ibudilast: A Non‐selective PDE Inhibitor with Multiple Actions on Blood Cells and the Vascular Wall

Preferential inhibition of human phosphodiesterase 4 by ibudilast

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