BACKGROUND/AIMS: Ulcerative colitis (UC) is a type of inflammatory bowel disease that mainly involves the colon. Thus far, glucocorticoids and amino-salicylate have been the main treatment.METHODS: To assess drugs with fewer side effects, this study evaluated the effects of sodium cromoglycate (SCG) on acetic acid-induced UC in rats. The treatment groups included SCG receivers (50 and 100 mg/kg, intra-orally) and sulfasalazine (SSZ) receivers (100 mg/kg, intra-orally). The colonic mucosal injury was assessed by clinical, macroscopic, and histopathological examinations.RESULTS: In the treatment groups with 50 and 100 mg/kg of SCG, the clinical activity score decreased to 2.67±0.18 and 1.73±0.21 (p<0.05), respectively, compared to the UC control group (3.21±0.31), and were higher than that of the group given the standard treatment of 100 mg/kg SSZ (1.10±0.09). The treatment groups with 50 and 100 mg/kg of SCG showed a lower clinical gross lesion score than the UC control group (2.91±0.28 and 2.10±0.43, vs. 4.49±0.61, p<0.05) and were higher than the standard group (0.95±0.18). Treatment with SCG (100 mg/kg) decreased the macroscopic scores significantly compared to the UC control group (p<0.05) on the 8th day.CONCLUSIONS: SCG (100mg/kg) decreased significantly the clinical activity score, gross lesion, and percentage-affected area compared to the UC controls on the 8th day.
Acetic Acid ; Animals ; Colitis, Ulcerative ; Colon ; Cromolyn Sodium ; Glucocorticoids ; Inflammatory Bowel Diseases ; Mice ; Rats ; Sodium ; Sulfasalazine ; Ulcer

This study evaluated the anti-asthmatic activities of 2,6-di-tert-butyl-4-hydroxymethylphenol (DBHP) that is a potent phenolic antioxidant in edible vegetable oil. The effects of DBHP on bronchial asthma were evaluated by determining the specific airway resistance (sRaw) and tidal volume (TV) during the immediate asthmatic response (IAR) and the late-phase asthmatic response (LAR) in guinea pigs with aerosolized ovalbumin-induced asthma. Recruitment of leukocytes and the levels of biochemical inflammatory mediators were determined in the bronchoalveolar lavage fluids (BALFs), and histopathological surveys performed in lung tissues. DBHP significantly inhibited the increased sRaw and improved the decreased TV on IAR and LAR, and also inhibited recruitment of eosinophils and neutrophils into the lung, and release of biochemical inflammatory mediators such as histamine and phospholipase A₂ from these infiltrated leukocytes, and improved pathological changes. However, anti-asthmatic activities of DBHP at oral doses of 12.5 to 50 mg/kg was less than those of dexamethasone (5 mg/kg, p.o.) and cromoglycate (10 mg/kg, p.o.), but more potent or similar to that of salbutamol (5 mg/kg, p.o.). These results in the present study suggest that anti-asthmatic effects of DBHP in the guinea pigs model of OVA-induced asthmatic responses principally are mediated by inhibiting the recruitments of the leukocytes and the release of biochemical inflammatory mediators from these infiltrated leukocytes.
Airway Resistance ; Albuterol ; Animals ; Asthma ; Bronchoalveolar Lavage Fluid ; Cromolyn Sodium ; Dexamethasone ; Eosinophils ; Guinea Pigs* ; Guinea* ; Histamine ; Leukocytes ; Lung ; Neutrophils ; Ovalbumin* ; Phenol ; Phospholipases ; Tidal Volume ; Vegetables

OBJECTIVETo investigate the effect of sodium cromoglycate on experimental endometriosis in rats.

METHODSEndometriosis model was established in 36 unpregnant female SD rats by transplanting autologous fragments of endometrium to the inner surface of the abdominal wall. The endometriotic lesions were measured by a second laparotomy 2 weeks after surgery. Then the rats were randomly divided into four groups (n=8 in each group) to receive intraperitoneal injection of different doses of sodium cromoglycate for 2 weeks: high-dose group (20 mg·kg⁻¹·d⁻¹); low-dose group (10 mg·kg⁻¹·d⁻¹); the negative control group and the blank control group. The animals were sacrificed and the size of the lesions were measured. The endometriosis model of SD rats was identified by HE staining and immunohistochemical staining of keratin and vimentin. The total number of mast cells and their degranulation were measured by Toluidine blue staining; the concentrations of TNF-α in serum were measured by enzyme linked immunosorbent assay; the concentrations of estradiol in serum were measured by enzyme immunoassay; the expression of tryptase and nerve growth factor (NGF) were measured by immunohistochemical staining.

RESULTSThe number of activated mast cells (MC) by Toluidine blue staining in high-dose group was significantly lower than that in negative control group (P<0.05), and its ratio of degranulation/total number of MC was significantly lower than that in negative control group or blank control group (P<0.05). The serum TNF-α levels and tryptase expression in tissues in high-dose group were significantly lower than those in negative control group or blank control group (P<0.05). However, no significant difference in the size of endometriotic lesions and expression of NGF was found among groups (P>0.05).

CONCLUSIONSodium cromoglycate can stabilize mast cells from degranulation, which may relieve the clinical symptoms of endometriosis by reducing TNF-α and tryptase levels.

Animals ; Cromolyn Sodium ; pharmacology ; Disease Models, Animal ; Endometriosis ; drug therapy ; Endometrium ; pathology ; Female ; Mast Cells ; drug effects ; Nerve Growth Factor ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tryptases ; metabolism ; Tumor Necrosis Factor-alpha ; blood

Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder
Allergy and Immunology ; Animals ; Comorbidity ; Cromolyn Sodium ; Food Hypersensitivity ; Humans ; Immunoglobulin E ; Inflammation ; Irritable Bowel Syndrome ; Mast Cells ; Methacholine Chloride ; Neurons ; Pilot Projects ; Skin

Human seminal plasma allergy is a rare phenomenon. Its clinical manifestations are diverse, and range from mild local pruritus to fatal anaphylaxis. Treatment varies with severity of the reactions: abstinence, condom usage or immunotherapy (subcutaneous or intravaginal) with seminal fluid. Local allergic reactions can be managed by prophylactic use of antihistamines or local cromolyn cream. A 33-year-old female visited the Asthma and Allergy Clinic in Seoul National University Bundang Hospital for the recurrent generalized urticarial reactions after sexual intercourse. She had been suffering from asthma, allergic rhinoconjunctivitis and atopic dermatitis for 10 years. She gave birth to a baby 6 months ago and no problem before. However, recently she began to recognize unexpected generalized urticaria that occurred after the sexual intercourse with husband. She wanted to have the second baby but hesitated because of the recurrent symptoms after the intercourse. She showed positive response to skin prick test with her husband's seminal fluid. The IgE-binding components were 15, 22, 28, and 35 kDa. Considering her moderate cutaneous reactions, we decided to try prophylactic treatments with oral anti-histamine one hour before sexual intercourse. She did not experience urticarial reactions with intercourse while oral anti-histamine was administered in advance. Finally, treatment outcome was successful, and the couple successfully gave birth to their second baby. We suppose that prophylactic antihistamine may be also applied in seminal plasma allergy patients if systemic reactions are limited to mild to moderate generalized urticaria.
Adult ; Anaphylaxis ; Asthma ; Coitus ; Condoms ; Cromolyn Sodium ; Dermatitis, Atopic ; Female ; Histamine Antagonists ; Humans ; Hypersensitivity ; Immunotherapy ; Parturition ; Pregnancy ; Pruritus ; Semen ; Seoul ; Skin ; Spouses ; Treatment Outcome ; Urticaria

OBJECTIVETo investigate the role of sodium cromoglycate in brain protection and its effects on brain tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) expressions after global cerebral ischemia-reperfusion (IR) injury in gerbils.

METHODSTwenty-four healthy male gerbils were randomized into 3 equal groups, namely the sham-operated group with isolation of the bilateral carotid arteries but without occlusion, IR injury model group with bilateral carotid artery occlusion, and sodium cromoglycate treatment group with bilateral carotid artery occlusion and sodium cromoglycate administration at 25 mg/kg via the lingual vein as soon as the reperfusion start with another dose 1 h later. The animals were then sacrificed and the thalamus were removed, fixed in 10% formaldehyde and sliced for observation under light microscope with HE staining. The rest brain tissues were prepared into homogenate to determine the content of TNF-alpha and IL-1beta. The right hemispheres of the gerbils were measured for wet weight and dry weight to calculate the water content in the brain.

RESULTSThe water content in the brain of the gerbils in the model group was the highest among the groups, and that in sodium cromoglycate treatment group was significantly less than that of the model group (P<0.05). Microscopic examination showed the most severe brain tissue damage in the model group with also the highest TNF-alpha and IL-1beta levels in the brain. The brain TNF-alpha and IL-1beta levels in sodium cromoglycate group were significantly decreased as compared with those in the model group (P<0.05).

CONCLUSIONSodium cromoglycate can alleviate brain IR injury possibly by lowering the TNF-alpha and IL-1beta levels in the brain tissues.

Animals ; Brain Ischemia ; metabolism ; Cromolyn Sodium ; pharmacology ; Gerbillinae ; Interleukin-1beta ; metabolism ; Male ; Neuroprotective Agents ; pharmacology ; Random Allocation ; Reperfusion Injury ; prevention & control ; Tumor Necrosis Factor-alpha ; metabolism

Neuropeptides are widely distributed throughout skin, gastrointestinal tracts, and nervous and immune systems. Neuropeptides act to mediate the vasodilation and induce mast cell activation in humans and rats in vitro. However, the mechanism of the cutaneous neuropeptides-induced mast cell activation and the extent of the vascular permeability by cutaneous neuropeptides are not fully understood. This issue was investigated by the injecting six cutaneous neuropeptides-atrial natriuretic peptide, calcitonin gene-related peptide, neuropeptide Y, somatostatin, substance P and vasoactive intestinal peptide-into the skin of rats and by treatment of six cutaneous neuropeptides in rat peritoneal mast cell (RPMC) in vitro. All of the cutaneous neuropeptides increased the significant vascular permeability by the injection into the back skin of normal rats. All of the cutaneous neuropeptides also induced the mast cell degranulation and the histamine release from RPMCs, in a dose-dependent pattern, and increased the calcium uptake and decreased the level of cAMP of RPMCs in vitro. The effects of cutaneous neuropeptides on the vascular permeability and mast cell activation were inhibited by mast cell stabilization agent, disodium cromoglycate. These findings show that cutaneous neuropeptides can induce the mast cell activation by not only increasing the calcium uptake and decreasing the level of cAMP in RPMCs, but also the increment of vascular permeability in the skin of rats.
Animals ; Calcitonin Gene-Related Peptide ; Calcium ; Capillary Permeability ; Cromolyn Sodium ; Gastrointestinal Tract ; Histamine ; Histamine Release ; Humans ; Immune System ; Mast Cells ; Neuropeptide Y ; Neuropeptides ; Rats ; Skin ; Somatostatin ; Substance P ; Vasodilation

Animals ; Cromolyn Sodium ; administration & dosage ; Disease Models, Animal ; Intestines ; blood supply ; Mast Cells ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; mortality ; pathology ; p-Methoxy-N-methylphenethylamine ; administration & dosage

The study established an HPLC-MS/MS method for determining the concentrations of sodium cromoglycate in human plasma and evaluated the pharmacokinetics of nasal drops and nasal spray. A C18 column was used to separate sodium cromoglycate in plasma with a mobile phase of a mixture of ammonium-methanol (involves 50% acetonitrile) (15:85) at a flow rate of 0.4 mL x min(-1). Electronic spray ionization (ESI) and multiple-reaction monitoring (MRM) were used for the determination of sodium cromoglycate in human plasma. The linear range of the standard curve of sodium cromoglycate was from 0.3 to 20 ng x mL(-1), and the minimum concentration of detection was 0.3 ng x mL(-1). The extraction recovery was more than 94.1%, intra-day and inter-day RSD were less than 14.3%. After a single dose of sodium cromoglycate, the main pharmacokinetic parameters of nasal spray and nasal drops were as follows, T(1/2)(1.82 +/- 0.54) h, (1.59 +/- 0.52) h; Tmax (0.47 +/- 0.12) h, (0.44 +/- 0.15) h; Cmax, (9.79 +/- 4.66) ng x mL(-1), (10.88 +/- 4.05) ng x mL(-1); AUC(0-5 h)(11.52 +/- 3.46) ng x mL(-1) x h x h, (12.63 +/- 4.23) ng x mL(-1) x h, Fr(93.6 +/- 13.8)%. The method is sensitive, rapid and accurate. It is suitable for therapeutic drug monitoring and human pharmacokinetic study of sodium cromoglycate.
Administration, Intranasal ; Anti-Allergic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; Cromolyn Sodium ; administration & dosage ; blood ; pharmacokinetics ; Drug Monitoring ; methods ; Humans ; Male ; Nebulizers and Vaporizers ; Quality Control ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVETo investigate cardiac function impairment and myocardial injury in rats with intestinal ischemia-reperfusion and the protective effect of cromolyn sodium.

METHODSThirty-two SD rats were randomized into 4 groups (n=8), namely the sham operation group, model group, 50 mg/kg cromolyn sodium group, and 25 mg/kg cromolyn sodium group. Intestinal damage was induced by clamping the superior mesenteric artery for 45 min followed by reperfusion for 60 min. Cromolyn Sodium was administrated intaperitoneally 15 min before reperfusion. The heart rate (HR), left ventricle pressure (LVSP), and the maximal/minimum rate of LVSP (+dp/dt(max), -dp/dt(max)) were sacrificed immediately before ischemia (baseline, T(0)), at 15 min (T(1)), 30 min (T(2)), 45 min (T(3)) of ischemia, and at 3 min (T(4)), 5 min (T(5)), 10 min (T(6)), 15 min (T(7)), 45 min (T(8)), 60 min (T(9)) of reperfusion. At the end of the experiment, the rats were executed and the hearts were immediately removed for observation of the pathological changes and determination of MDA contents and SOD activity.

RESULTSCompared with the baseline T(0), the HR, +dp/dt(max), -dp/dt(max) and the LVSP were decreased significantly at T(8) and T(9) in the model group and the two cromolyn sodium groups (P<0.05). Compared with the sham operation group, these indices were also significantly decreased at T(8) and T(9) in the model group and the two cromolyn sodium groups, but the model group had significantly lower levels for these indices at T(8) and T(9) than the two cromolyn sodium groups (P<0.05). The score of myocardial injury in the model group and the two cromolyn sodium groups were significantly higher than that of group A, and 50 mg/kg cromolyn sodium group had lower score than the model group (P<0.05). The rats in the model group had significantly higher MDA levels than those in the sham operation group and the 50 mg/kg cromolyn sodium group. SOD activities in the model group and 25 mg/kg cromolyn sodium group was lower than that in the sham operation group (P<0.05), but 50 mg/kg cromolyn sodium group had significantly higher SOD activities than the model group (P<0.05).

CONCLUSIONCromolyn sodium can protect the myocardium against intestal ischemia-reperfusion injury and improve the cardiac function.

Animals ; Cardiotonic Agents ; pharmacology ; Cromolyn Sodium ; pharmacology ; Female ; Heart ; drug effects ; physiopathology ; Heart Rate ; drug effects ; Intestines ; blood supply ; Male ; Malondialdehyde ; blood ; metabolism ; Myocardium ; metabolism ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; blood ; prevention & control ; Superoxide Dismutase ; blood ; metabolism ; Time Factors