Involvement of leukotriene C4 in PAF-induced death in mice

Tsunoda, Hajime; Abe, S.; Sakuma, Y.; Katayama, Satoshi; Katayama, Kouichi

doi:10.1016/0952-3278(90)90008-9

Cited by 13 publications

(4 citation statements)

References 12 publications

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“…Data from in vivo studies suggest that E6080 is a potent 5-lipoxygenasc inhibitor, as already reported [12][13][14], In this in vitro study, it was confirmed that E6080 inhibited the Ag-induced LT release from passively sensitized guinea-pig and human lung fragments and from human basophils, as well as the calcium ionophore A23187-induced LT release from human PMNs and the LTC4 release from rat alveolar macrophages, exposed to phagocytotic stimulation with silica particles.…”

Section: Discussionsupporting

confidence: 66%

“…Data from in vivo studies suggest that E6080 is a potent 5-lipoxygenase inhibitor, as already reported [12][13][14]. In this study, we confirmed the in vitro effects of a newly de veloped 5-lipoxygenase inhibitor, E6080 [6-hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazole hy drochloride], on LT release and compared them with those of AA861 [2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-l, 4-benzoquinone], a specific and potent 5-lipoxygenase inhibitor [15,16].…”

Section: Introductionmentioning

confidence: 50%

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Effects of the New 5-Lipoxygenase Inhibitor E6080 on Leukotriene Release in vitro

Sakuma¹,

Katayama²,

Tsunoda³

et al. 1992

Int Arch Allergy Immunol

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Fundamental studies were conducted to examine the release of histamine and leukotriene (LT) C₄ from lung fragments of guinea pigs and the effects of E6080 on the release of LTB₄ and LTC₄ from lung fragments or inflammatory cells. The release of histamine and LTs showed large interindividual variations and a marked dependence on experimental conditions. Addition of 10 mML-cysteine significantly increased LTC₄ release compared with that in its absence (about 1.7 times, in terms of mean value). E6080 inhibited antigen-stimulated LTB₄ and LTQ release from passively sensitized human (IC₅₀: LTB₄ 0.08 µM, LTC₄ 0.2 µM) and guinea-pig lung fragments (IC₅₀: LTQ 1.1 µM). The LTB₄ and LTQ releases from healthy human polymorphonuclear leukocytes (calcium ionophore A23187) and from allergic patients’ leukocytes (basophils, antigen) were inhibited by E6080 with IC₅₀ values of below 1.0 µM Furthermore, the LTQ release from rat alveolar macrophages (silica particles) was inhibited by E6080 with an IC₅₀ of 0.2 µM The potent inhibition by E6080 might be a result of the inhibition of 5-lipoxygenase, since 5-lipoxygenase in rat basophilic leukemia cell was inhibited by E6080 with an IC₅₀ of 0.2 µM The results confirm the potent inhibitory effects of E6080 on the release of LTs.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 50%

Effects of the New 5-Lipoxygenase Inhibitor E6080 on Leukotriene Release in vitro

Sakuma¹,

Katayama²,

Tsunoda³

et al. 1992

Int Arch Allergy Immunol

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“…into mice activates the A A cascade producing enough 5-LO products to cause death within one hour [7]. W h e n tested in a model of P A F -i n d u c e d mortality, C G S 26529 dose-dependently protected mice when administered at 2, 6 and 18 hr before P A F injection.…”

Section: Resultsmentioning

confidence: 99%

“…The model is useful for evaluating the inflammatory responses of leukocyte mobilization and plasma exudation. PAF-induced mortality, a modification of the method of Tsunoda [7], was used to determine oral activity in mice. Table 1 (Table 2).…”

Section: Ex Vivo and In Vivo Studiesmentioning

confidence: 99%