Effect Of Cromoglycate Research Articles

The role of nitric oxide and sulphydryls in gastric mucosal protection induced by sodium cromoglycate in rats.

The role of endogenous nitric oxide and sulphydryls in gastric protection afforded by sodium cromoglycate against ethanol-induced gastric lesions was studied in rats. Drugs were administered either intraperitoneally (i.p.) or subcutaneously (s.c.) 30, 45 or 60 min before oral administration of ethanol. Administration of cromoglycate before ethanol dose-dependently inhibited ethanol-induced gastric lesions. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide biosynthesis, dose-dependently aggravated gastric lesions and reduced cromoglycate-induced gastric protection. The attenuating effect of L-NAME on gastric protection elicited by cromoglycate was reversible by pretreatment with L-arginine but not by D-arginine. On the other hand, ethanol-induced gastric lesions were found to be associated with a reduction of nonprotein sulphydryl content of glandular stomachs. Pretreatment with cromoglycate prevented non protein sulphydryl depletion and afforded protection. Pretreatment with N-ethylmaleimide, a sulphydryl blocker, caused dose-dependent enhancement of ethanol-induced gastric lesions and further depletion of non protein-sulphydryl. Treatment with N-ethylmaleimide before cromoglycate reduced the gastric protection that was associated with depletion of nonprotein sulphydryls. Furthermore, combined N-ethylmaleimide and L-NAME pretreatment caused a greater aggravation of ethanol-induced gastric lesions and significantly produced a higher reduction of the protective effects of cromoglycate. However, pretreatment with L-arginine only partially restored the protective effects of cromoglycate. These results suggest that the protective effects of cromoglycate may be dependent on the maintenance of a critical level of both endogenous nitric oxide and nonprotein sulphydryls in the gastric mucosa.

Mast Cell Stabilization Reduces Hemorrhage Formation and Mortality After Administration of Thrombolytics in Experimental Ischemic Stroke

Thrombolysis with tissue plasminogen activator (tPA) improves stroke outcome, but hemorrhagic complications and reperfusion injury occasionally impede favorable prognosis after vessel recanalization. Perivascularly located cerebral mast cells (MCs) release on degranulation potent vasoactive, proteolytic, and fibrinolytic substances. We previously found MCs to increase ischemic and hemorrhagic brain edema and neutrophil accumulation. This study examined the role of MCs in tPA-mediated hemorrhage formation (HF) and reperfusion injury. Exposure to tPA in vitro induced strong MC degranulation. In vivo experiments in a focal cerebral ischemia/reperfusion model in rats showed 70- to 100-fold increase in HF after postischemic tPA administration (P<0.001). Pharmacological MC stabilization with cromoglycate led to significant reduction in tPA-mediated HF at 3 (97%), 6 (76%), and 24 hours (96%) compared with controls (P<0.01, P<0.001, and P<0.01, respectively). Furthermore, genetically modified MC-deficient rats showed similarly robust reduction of tPA-mediated HF at 6 (92%) and 24 (89%) hours compared with wild-type littermates (P<0.01 and P<0.001, respectively). MC stabilization and MC deficiency also significantly reduced other hallmarks of reperfusion injury, such as brain swelling and neutrophil infiltration. These effects of cromoglycate and MC deficiency translated into significantly better neurological outcome (P<0.01 and P<0.05, respectively) and lower mortality (P<0.05 and P<0.05, respectively) after 24 hours. MCs appear to play an important role in HF and reperfusion injury after tPA administration. Pharmacological stabilization of MCs could offer a novel type of therapy to improve the safety of administration of thrombolytics.

The effect of cromoglycate on time-dependent histamine and serotonin concentrations in stored blood products

Biogenic amines, having vascular and inflammatory effects, are accepted as a potential threat for some non-hemolytic transfusion reactions. The aim of this study was to investigate time-dependent histamine/serotonin levels in stored blood products and to see whether cromoglycate has any effect on these mediators. Either for platelet or whole blood, 10-fold concentrations of cromoglycate (1 μg ml −1, 10 μg ml −1, 100 μg ml −1) with controls prepared as pairs of replicate bags collected from two healthy subjects, separately. By using enzyme immunoassay, histamine and serotonin levels were determined in platelet or blood replicates. Histamine levels increased significantly with time but serotonin remained unchanged during the storage of platelet or blood specimens. Cromoglycate had no effect on these biogenic amines except an increase of serotonin in whole blood specimens containing 100 μg ml −1 of it. So, cromoglycate cannot protect blood products against rising levels of histamine or serotonin.

Changes induced by sodium cromoglycate in brain catecholamine turnover in morphine dependent and abstinent mice.

The effects of sodium cromoglycate (CRO) were studied in relation to the metabolism of brain catecholamines: dopamine (DA) and noradrenaline (NA), and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG). CRO was injected SC in control mice, morphine-tolerant mice (tolerance was induced by SC implantation of a 75 mg morphine pellet; CRO was administered on day 4 of addiction) and 30 min before abstinence (withdrawal was induced by SC injection of naloxone (1 mg/kg) on day 4 of addiction). Brain catecholamines and their metabolites were measured using high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD), for DA, NA, DOPAC and HVA, and coupled with fluorescence detection for MHPG. The ratios of DOPAC + HVA/DA and MHPG/NA were kept as an index of DA and NA turnovers, respectively. CRO administered 30 min before naloxone-precipitated withdrawal diminished significantly NA levels in frontal cortex. CRO increased DA turnover in striatum and frontal cortex in naive animals and significantly diminished DA levels in frontal cortex and DOPAC levels in frontal cortex and midbrain in morphine-dependent mice. These findings are discussed in relation to the protective effects of CRO on opiate withdrawal and the effects of CRO on locomotor activity.

Effect of Cromoglycate on Gas Changes, During Bronchial Challenge by UNCDW in Children with Asthma

Eighteen asthmatic children were challenged with ultrasonically nebulized cold distilled water (UNCDW). Blood gas composition was monitored transcutaneously (tcpO2 and tcpCO2) during and after the challenge. Assuming as basal the response to this UNCDW test, nine children (Group A) were then chosen at random to inhale cromoglycate by aerosol delivery for 8 days. Nine children (Group B), acting as a control, inhaled saline for 8 days. At the end of this therapy, each child repeated the UNCDW test. Statistical analysis with t-test for paired data was used to compare the results of each child to both tests. Mean basal tcpO2 and tcpCO2 were all within the expected normal range. In all children, both mean tcpO2 and tcpCO2 were reduced during and after UNCDW inhalation. Mean tcpCO2 values during the challenge were significantly (p < 0.001) lower than the corresponding steady state 2 rain after the UNCDW challenge, with a mean drop of −7% (2.1 S.D.). Mean tcpO2 values remained significantly decreased (p < 0.001) from the fifth mitt of the UNCDW challenge to the end of the observation period, with a mean drop of −20% (15.5 S.D.). After treatment with cromoglycate (Group A), the mean tcpCO2 values during UNCDW did not change significantly from those ofsteady state conditions: −0.8% (0.5 S.D.); whereas mean tcpO2 values decreased by −4% (4.9 S.D.). The control children treated with saline (Group B) showed mean tcpCO2 and tcpO2 values which were significantly different (p < 0.001) from those of the steady state conditions: mean drop of tcpCO2, −6% (4.2 S.D.); mean drop of tcpO2, −20% (4.7 S.D.). In conclusion, it emerges that: UNCDW induces nonspecific broncho-constriction in asthmatic children with a typical drop of tcpCO2 and tcpO2; the treatment with cromoglycate normalizes the time course of tcpCO2 (hyper-reactivity) and reduces dramatically the drop of tcpO2 time course (hyper-responsivity) during and after the UNCDW test.

Kinetics of the inhibitory effect of flavonoids on histamine secretion from mast cells

The effect of cromoglycate and of natural flavonoids on histamine release from peritoneal rat mast cells induced by compound 48/80 and ionophore A23187 was studied according to preincubation time of mast cells with drugs and to incubation time of cells with the triggering agent. Preincubation of cells with cromoglycate, dihydroquercetin and amentoflavone, a biflavonoid, decreased the potency of drugs to inhibit the ionophore-induced release; the optimal inhibitions were observed when drugs were added simultaneously with the ionophore A23187. In contrast, a short preincubation (2 min) of cells with quercetin or luteolin decreased their inhibitory effect on the ionophore-induced release, whereas a longer preincubation increased the inhibition. When compound 48/80 was used to trigger histamine secretion, the inhibitory potencies of all the compounds used were decreased according to preincubation time. Dihydroquercetin (taxifolin), previously considered as inactive, showed an interesting cromoglycate-like behaviour.

The effect of disodium cromoglycate on rectal mucosal histamine release, eosinophil exudation and disease activity in active ulcerative colitis.

Disodium cromoglycate has been reported to benefit some patients with active ulcerative colitis. We have investigated the effect of cromoglycate in high dose on rectal mucosal mast cell degranulation (assessed indirectly by measurement of mucosal histamine release, using in vivo rectal dialysis, and the eosinophil content of the rectal inflammatory exudate) and on disease activity in eight patients in relapse. Although cromoglycate (1600 mg by mouth daily for 2 weeks) did not affect histamine release, it reduced (P less than 0.05) the eosinophil content of the exudate towards normal. Stool frequency also fell (P less than 0.05) but other aspects of bowel habit, sigmoidoscopic appearance, rectal mucosal potential difference and electrolyte transport were unaltered. Pre-treatment values of histamine release and eosinophil exudation could not be used to predict the response to cromoglycate. The reduction in eosinophil exudation produced by the drug could be due to inhibition of mast cell release of chemotactic factors other than histamine; the therapeutic effect of cromoglycate was unimpressive.

Inhibitory Effects of Cromoglycate and Theophylline on Rat Macrophage and Mast-Cell Cyclic Nucleotide Phosphodiesterase

Inhibitory Effects of Cromoglycate and Theophylline on Rat Macrophage and Mast-Cell Cyclic Nucleotide Phosphodiesterase

Proceedings: Effect of cromoglycate and eicosatetraynoic acid on the release of prostaglandins and SRS-a from immunologically challenged guinea pig lungs.

Proceedings: Effect of cromoglycate and eicosatetraynoic acid on the release of prostaglandins and SRS-a from immunologically challenged guinea pig lungs.

Effect of cromoglycate on anaphylactic histamine release from rat peritoneal mast cells.

Cromoglycate (1-30 muM) produced a concentration-dependent inhibition of anaphylactic histamine release from actively sensitized rat peritoneal mast cells but at lower concentrations (0.01-0.1 muM) occasionally produced a concentration-dependent enhancement of histamine release.