Sulfur mustard induced mast cell degranulation in mouse skin is inhibited by a novel anti-inflammatory and anticholinergic bifunctional prodrug
Laurie B. JosephGabriella CompostoRoberto M. PerezHong-Duck KimRobert P. CasillasNed D. HeindelSherri C. YoungC. Jeffrey LaceyJaya SaxenaChristophe GuillonClaire R. CroutchJeffrey D. LaskinDiane E. Heck
16
Citation
58
Reference
10
Related Paper
Citation Trend
Keywords:
Sulfur mustard
Cassia occidentalis Linn. mast cell degranulation at a dose of 250 mg/kg, showed dose dependent stabilizing activity towards human RBC, with is widely used in traditional medicine of India to treat a number of clinical conditions including allergy and inflammatory manifestations. In the present study anti-allergic, anti-inflammatory and anti-oxidant properties of C. occidentalis whole plant ethanolic extract (CO) was investigated. Effects of CO on rat mast cell degranulation inhibition and human red blood cell (HRBC) membrane stabilization were studied in vitro following standard methods. The anti lipidperoxidant effects of CO were also studied in vitro. Effect of CO on carrageenan-induced mouse paw oedema inhibition was also assessed. CO significantly decreased maximum protection of 80.8% at 15 microg/ml. The extract also caused significant reduction in malondialdehyde (MDA) levels of murine hepatic microsomes at 100 microg/ml (56%) and significantly reduced carrageenan induced inflammation in mice at a dose of 250 mg/kg. Results of the present study indicated that CO inhibited mast cell degranulation, stabilized HRBC membrane thereby alleviating immediate hypersensitivity besides showing anti oxidant activity.
Carrageenan
Anti-inflammatory
Malondialdehyde
Cite
Citations (24)
Curine is a bisbenzylisoquinoline alkaloid and the major constituent isolated from Chondrodendron platyphyllum, a plant that is used to treat inflammatory diseases in Brazilian folk medicine. This study investigates the effectiveness of curine on mast cell-dependent responses in mice.To induce mast cell-dependent responses, Swiss mice were subcutaneously sensitized with ovalbumin (OVA-12 μg/mouse) and Al(OH)3 in a 0.9% NaCl solution. Fifteen days later, the animals were challenged with OVA through different pathways. Alternatively, the animals were injected with compound 48/80 or histamine, and several parameters, including anaphylaxis, itching, edema and inflammatory mediator production, were analyzed. Promethazine, cromoglycate, and verapamil were used as control drugs, and all of the treatments were performed 1h before the challenges.Curine pre-treatment significantly inhibited the scratching behavior and the paw edema induced by either compound 48/80 or OVA, and this protective effect was comparable in magnitude with those associated with treatment with either cromoglycate or verapamil. In contrast, curine was a weak inhibitor of histamine-induced paw edema, which was completely inhibited by promethazine. Curine and verapamil significantly inhibited pleural protein extravasations and prostaglandin D2 (PGD2) and cysteinyl leukotrienes (CysLTs) production following allergen-induced pleurisy. Furthermore, like verapamil, curine inhibited the anaphylactic shock caused by either compound 48/80 or an allergen. In in vitro settings, these treatments also inhibited degranulation as well as PGD2 and CysLT production through IgE-dependent activation of the mast cell lineage RBL-2H3.Curine significantly inhibited immediate allergic reactions through mechanisms more related to mast cell stabilization and activation inhibition than interference with the pro-inflammatory effects of mast cell products. These findings are in line with the hypothesis that the alkaloid curine may be beneficial for the treatment of allergic disorders.
Cite
Citations (19)
To clarify the mechanism of action of 5- [4- (2-carboxyethylcarbamoyl) -phenylazo] -salicylic acid disodium salt dehydrate (BX661A) as a therapeutic drug for ulcerative colitis, we investigated the effects on carrageenin edema, adjuvant arthritis, polymorphonuclear leukocyte (PMN) chemotaxis and degranulation of mesenteric mast cell, and following results were obtained.1. Although BX661A, salazosulfapyridine (SASP), 4-aminobenzoyl-β-alanine (4-ABA) and sulfapyridine (SP) did not inhibit the carrageenin edema at pretreatment for 30 min, BX661A and SASP showed the inhibitory effect on carrageenin edema at pretreatment for 8 hrs.2. SASP showed the slight therapeutic effect on adjuvant arthritis, but BX661A and 5-aminosalicylic acid (5-ASA) had no effect.3. BX661A, SASP and SP dose-dependently inhibited the PMN chemotaxis induced by zymosan-treated serum, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4) . 4-ABA only inhibited the FMLP-induced chemotaxis. On the other hand, 5-ASA at concentration up to 10 mM exhibited almost no effects on all PMN chemotaxis.4. BX661A, SASP and SP dose-dependently inhibited the mast cell degranulation induced by compound 48/80, substance P and IgE. 5-ASA showed the inhibitory effects on compound 48/80 and IgE-induced mast cell degranulation, but 4-ABA only inhibited the IgE-induced degranulation.From these results, it was suggested that inhibitory effect of BX661A on carrageenin-induced edema may be due to 5-ASA, further that inhibitory effects on PMN chemotaxis activity and degranulation of mesenteric mast cell partially may be concerned in therapeutic effects of BX661A on ulcerative colitis.
Leukotriene B4
Aminosalicylic acid
Cite
Citations (0)
Antiallergic effects of 4-[2-oxo-3-(1H-tetrazol-5-yl)-2H-chromen-8-yloxy]-buty ric acid (C4C) were studied. C4C is an active principal metabolite of an orally effective antiallergic agent, KP-136. C4C (0.2-1 mg/kg, i.v.) markedly inhibited the mast cell-mediated homologous PCA of rats and the experimental allergic asthma of rats and guinea pigs, although it had almost no effects on heterologous PCA and compound 48/80-induced cutaneous response in rats. C4C (0.2 mg/kg, i.v.) was scarcely effective on cutaneous responses induced by intradermal injection of histamine and serotonin which are principal chemical mediators of rat homologous PCA, and it blocked the decrease of skin histamine content after the PCA. In addition, C4C (0.01-0.5 micrograms/ml) inhibited the increase of 45Ca uptake of mast cells, the histamine release and the degranulation induced by the antigen-antibody interaction. These effects of C4C were much the same as those of KP-136. From the above findings, C4C is considered to be an antiallergic agent that inhibits the mast cell activation by blocking the calcium influx, and it shares similar pharmacological properties with KP-136.
Heterologous
Compound 48/80
Intradermal injection
Cite
Citations (5)
Bronchial asthma is a chronic inflammatory disorder of the airways associated with reversible airway obstruction and increased airway responsiveness to a variety of stimuli. An intuitive inference from this definition is that a causal relationship may exist between airway inflammation and airway hyperresponsiveness. It can be say that "airway inflammation equal to airway hyperresponsiveness". Attachment of antigen antibody complex to the mast cell causes its disruption and release of inflammatory mediators such as histamine.To evaluate the efficacy of anti-asthmatic property of a drug, evaluation of anti-histaminic, mast cell stabilizing and bronchodilator property can be use as pharmacodynamic parameter. Bharangyadi is a polyherbal compound having Bharangi (Clerodendrum serratum), Sati (Hedychium spicatum) and Pushkarmoola (Inula racemosa) as ingredient herbs The present study aimed to evaluate the anti-asthmatic activity of an indigenous polyherbal compound Bharangyadi through various in-vitro & in-vivo experimental models.The results demonstrate that drug has potent histamine antagonism property with significant mast cell stabilizing and spasmolytic activity in the experimental animals. Compound 48/80, a potent mast cell degranulator, provoked 76% degranulation of mast cells in the control group. Ethanolic extract of Bharangyadi at the doses 500 and 1000 μg/ml protected from compound 48/80-evoked degranulation (P < 0.01) in dose dependent manner.Pre-treatment with Bharangyadi extract showed 80% & 86% protection from histamine induced bronchoconstriction in guinea pigs with 27.8% and 36.1% increase in preconvoulsion time (equal to standard drug). Screening of Histamine antagonism activity on guinea pig ileum showed that drug reduces the smooth muscle contraction in dose dependent manner. Increasing concentration of Bharangyadi extract with maximum dose of histamine (1.6μg) showed maximum inhibition at the dose of 50mg (99.78%). Inhibition of smooth muscle contraction by addition of drug in organ bath before adding histamine showed that drug has preventive type antagonism.
Compound 48/80
Cite
Citations (24)
Bothrops
Cite
Citations (31)
Terminalia chebula
Salvia miltiorrhiza
Compound 48/80
Cite
Citations (0)
The inhibitory effect of the two H<sub>1</sub> antagonists clemastine and loratadine on histamine release in human skin was studied in 15 volunteers. The antihistamines and placebo were administered orally (clemastine 2 mg twice a day, loratadine 10 mg once a day) for 5 days according to a double-blind, crossover design. Clemastine caused a significant sedation in comparison with placebo, whereas there was no difference between loratadine and placebo in this respect. After 5 days’ medication, flare reaction was induced by intradermal injection of histamine and the histamine liberator compound 48/80. The antihistamine dosages were approximately equipotent and inhibited the flare response induced by histamine to about the same extent, whereas the flares induced by compound 48/80 were still more inhibited by both drugs. The results indicate that clemastine and loratadine not only inhibit histamine effects at H<sub>1</sub> receptor level, but have additional suppressive effects, probably due to inhibition of mast cell degranulation. The simple, virtually noninvasive, in vivo technique described in this paper does not require chemical analysis of the released mediators and could be used to screen ‘mast cell stabilizing’ effects of various antihistamines.
Loratadine
Astemizole
Cite
Citations (15)
Sulfur mustard
Cite
Citations (16)
Gardenia jasminoides
Gardenia
Cite
Citations (69)