Pretreatment with Evans blue, a stimulator of BKCa channels, inhibits compound 48/80-induced shock, systemic inflammation, and mast cell degranulation in the rat

Fu, Yaw-Syan; Kuo, Su-Yu; Lin, H.T.; Chen, Chunlin; Huang, Shiying; Wen, Zhi‐Hong; Lee, Kun‐Ze; Huang, Hung‐Tsai

doi:10.1007/s00418-015-1332-4

Cited by 8 publications

(4 citation statements)

References 22 publications

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“…As observed in this work, other authors also demonstrated the efficiency of C48/80 in inducing anaphylactoid shock in mice (14,27,28), rats (15,29), guinea pigs (30), rabbits (18), and pigs (9). The ability of C48/80 to promote a direct release of nitric oxide from endothelial cells was confirmed by a significant increase in nitric oxide plasma levels.…”

Section: Discussionsupporting

confidence: 81%

Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock

Albuquerque

Ferreira

Carvalho

et al. 2020

Braz J Med Biol Res

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Anaphylactic shock can be defined as an acute syndrome, and it is the most severe clinical manifestation of allergic diseases. Anaphylactoid reactions are similar to anaphylactic events but differ in the pathophysiological mechanism. Nitric oxide (NO) inhibitors during anaphylaxis suggest that NO might decrease the signs and symptoms of anaphylaxis but exacerbate associated vasodilation. Therefore, blocking the effects of NO on vascular smooth muscle by inhibiting the guanylate cyclase (GC) would be a reasonable strategy. This study aimed to investigate the effects of NO/cGMP pathway inhibitors methylene blue (MB), N o-nitro-L-arginine methyl ester hydrochloride (L-NAME), and indigo carmine (IC) in shock induced by compound 48/80 (C48/80) in rats. The effect was assessed by invasive blood pressure measurement. Shock was initiated by C48/80 intravenous bolus injection 5 min before (prophylactic) or after (treatment) the administration of the inhibitors MB (3 mg/kg), L-NAME (1 mg/kg), and IC (3 mg/kg). Of the groups that received drugs as prophylaxis for shock, only the IC group did not present the final systolic blood pressure (SBP) better than the C48/80 group. Regarding shock treatment with the drugs tested, all groups had the final SBP similar to the C48/80group. Altogether, our results suggested that inhibition of GC and NO synthase in NO production pathway was not sufficient to revert hypotension or significantly improve survival.

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Section: Discussionsupporting

confidence: 81%

Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock

Albuquerque

Ferreira

Carvalho

et al. 2020

Braz J Med Biol Res

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“…As a BK Ca (large-conductance Ca 2+ -activated K + channel) stimulator, Evans blue can induce Ca 2+ -dependent outward currents in sheep bladder myocytes (Fu et al, 2015). Cytosolic calcium is essential for HBV replication, core assembly, and induction of cell death (Choi et al, 2005; Xia et al, 2006; Geng et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

Evans Blue Inhibits HBV Replication Through a Dual Antiviral Mechanism by Targeting Virus Binding and Capsid Assembly

et al. 2019

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Chronic hepatitis B (CHB) is a global health problem caused by human hepatitis B virus (HBV). Current treatment with interferons and nucleos(t)ide analogs (NAs) can cause population tolerance and drug resistance. Therefore, new antiviral drugs, especially those targeting host factors, are urgently needed. Here, we identified Evans blue as a new HBV inhibitor by screening an FDA drug library using Huh7DhNTCP cells and confirmed the antiviral activity in primary human hepatocytes and human sodium taurocholate cotransporting polypeptide (hNTCP)-transfected porcine primary hepatocytes. Our efficacy study showed that Evans blue has an IC50 of 2 μM against HBV infection in Huh7DhNTCP cells, and no apparent toxicity at up to 1000 μM. The IC50 of Evans blue against HBV in primary human hepatocytes was approximately 5 μM. Mechanism studies revealed that Evans blue has a dual anti-HBV effect. It inhibits both the binding of viral preS1 to host cells through the host factor NTCP and the virus capsid assembly by targeting the host factor BK channel. The KD of the direct interaction between Evans blue and NTCP is 8.82E-8 M. Evans blue can suppress capsid assembly at micromolar concentrations by reducing the cytosolic calcium ion concentration. Since the antiviral effects on HBV binding and assembly are both achieved through targeting host factors, Evans blue inhibits the infection of nucleos(t)ide analog drug-resistant HBV strains in Huh7DhNTCP cells. Taken together, our results suggest that Evans blue may be a promising anti-HBV drug candidate in the classes of both entry and assembly inhibitors.

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“…The second pathway, mast cells can be activated with nonimmunogenic stimuli such as spermine, neuropeptides substance P, and C48/80 44 . It has been identified that intraperitoneal injection of C48/80 to the rat causes mast cell degranulation associated with histamine release in the mesentery 45 . Furthermore, it has been reported that P815 cells and RBL-2H3 cells are induced to degranulate in response to compound 48/80, releasing histamine and β-hexosaminidase respectively 46 .…”

Section: Discussionmentioning

confidence: 99%

The antinociception of oxytocin on colonic hypersensitivity in rats was mediated by inhibition of mast cell degranulation via Ca2+-NOS pathway

Gong

Tang

et al. 2016

Sci Rep

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This study was conducted to investigate the effects of oxytocin (OT) on visceral hypersensitivity/pain and mast cell degranulation and the underlying mechanisms. We found that oxytocin receptor (OTR) was expressed in colonic mast cells in humans and rats, as well as in human mast cell line-1 (HMC-1), rat basophilic leukemia cell line (RBL-2H3) and mouse mastocytoma cell line (P815). OT decreased 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity, colonic mast cell degranulation and histamine release after mast cell degranulation in rats. Also, OT attenuated the compound 48/80 (C48/80)-evoked histamine release in P815 cells and inward currents, responsible for the mast cell degranulation, in HMC-1, RBL-2H3 and P815 cells. Moreover, these protective effects of OT against visceral hypersensitivity and mast cell degranulation were eliminated by coadministration of OTR antagonist atosiban or a nonselective inhibitor of nitric oxide synthase (NOS), NG-Methyl-L-arginine acetate salt (L-NMMA). Notably, OT evoked a concentration-dependent increase of intracellular Ca2+ in HMC-1, RBL-2H3 and P815 cells, which was responsible for the activation of neuronal NOS (NOS1) and endothelial NOS (NOS3). Our findings strongly suggest that OT might exert the antinociception on colonic hypersensitivity through inhibition of mast cell degranulation via Ca2+-NOS pathway.

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Pretreatment with Evans blue, a stimulator of BKCa channels, inhibits compound 48/80-induced shock, systemic inflammation, and mast cell degranulation in the rat

Cited by 8 publications

References 22 publications

Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock

Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock

Evans Blue Inhibits HBV Replication Through a Dual Antiviral Mechanism by Targeting Virus Binding and Capsid Assembly

The antinociception of oxytocin on colonic hypersensitivity in rats was mediated by inhibition of mast cell degranulation via Ca2+-NOS pathway

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