Histamine-induced Bronchospasm In Guinea Pigs Research Articles

EVALUATION OF ANTI-ASTHMATIC ACTIVITY OF CAPPARIS DECIDUA

Objective: The present study was conducted to determine the anti-asthmatic activity of Capparis decidua.Methods: The acute oral toxicity study was conducted as per OECD guidelines, and the extract was proved to be safe up to the dose of 2000 mg/kg.The anti-asthmatic activity of C. decidua was evaluated using various experimental models such as histamine-induced bronchoconstriction in guineapigs and milk-induced leukocytosis in mice, histamine-induced bronchospasm in guinea pigs, studies on pre convulsive time and milk-inducedleukocytosis in mice, studies on blood.Results: Antihistaminic drugs Chlorpheniramine maleate and ethanolic extract of C. decidua significantly protected the guinea pigs against histamineinducedbronchospasm. The ethanolic section of C. decidua has dramatically prolonged the latent period of convulsions compared to control. Ethanolicextract of C. decidua suppresses the milk-induced leukocytosis by stabilizing the oxidative stress in the surrounding tissue.Conclusion: The results obtained in the above study suggest the ethanolic extract of C. decidua possesses significant anti-asthmatic activity.

Bronchodilatory effect of <i>Zingiber officinale</i> Roscoe (ginger) in guinea pigs

Purpose: To determine the bronchodilatory effect of ginger on histamine-induced bronchospasm in guinea pigs.
 Methods: Thirty-six guinea pigs weighing 400 - 700 g were randomly divided into six groups. Group 1 received distilled water, while group 2 was given formoterol (1.55 μg/kg) + budesonide (0.02 mg/kg). Guinea pigs in groups 3 and 4 were given ginger (350 and 700 mg/kg, respectively), while those in groups 5 and 6 received ginger (350 and 700 mg/kg, respectively) in addition to formoterol (1.55 μg/kg) and budesonide (0.02 mg/kg). Pre-convulsion time and percent protection in each group was calculated.
 Results: There was statistically significant improvement in pre-convulsion times, with values of 156.64 ± 32.93, 299.33 ± 44.20, and 235.99 ± 34.55 s for groups 2, 5 and 6, respectively (p < 0.01). Moreover, statistically significant protection values of 73 and 68 % were obtained for groups 5 and 6, respectively, relative to normal control (p < 0.01).
 Conclusion: These results indicate that ginger has promising potential for use as an add-on treatment for bronchospasm.
 Keywords: Zingiber officinale, Histamine, Asthma, Pre-convulsion time

Evaluation of the Antiasthmatic Activity of Methanolic Extract of Trigonella Foenum Graecum on Experimental Models of Bronchial Asthma

The present study deals with the phytochemical screening and evaluation of antiasthmatic activity of methanolic extract of Trigonella foenumgraecum on experimental models of bronchial asthma and anaphylaxis. The antiasthmatic activity was studied on histamine-induced bronchospasm in guinea pig (Dunkey-Hartley) for respiratory parameters such as maximum airflow, minimum airflow, tidal volume, respiratory rate, minute volume, specific airway resistance determination on double chambered whole body plethysmography on un-anesthetized guinea pigs, for mast cell degranulation by compound 48/80 (in vitro) was done using rat (Albino Wistar) peritoneal fluid. Trigonella foenum graecum treated result indicated significant protection against histamine-induced bronchospasm in guinea pigs at highest dose i.e. 400mg/kg. The bronchodilatory effect of Trigonella foenum graecum was found comparable to the protection offered by the standard drug Salbutamol on respiratory parameters in double chambered whole body plethysmography, Treatment with Trigonella foenum graecum at a dose of 400mg/kg showed a significant decrease in degranulation rate of actively and passively sensitized mast cells of sensitized rats when challenged with antigen. Trigonella foenum graecum. Possess significant anti-asthmatic activity due to its potential anti inflammatory, antioxidant and the antihistaminic activity, which reflects as anti-degranulating effect on mast cells and on respiratory parameters.
 Keywords: Trigonella foenum graecum; asthma; mast cell; compound 48/80; histamine

MOMORDICA CHARANTIA NANO DRY POWDER ORAL FORMULATION IN CONTROLLING HISTAMINE-INDUCED BRONCHOSPASM

Objective: Momordica charantia (MC) (bitter gourd) is known traditionally to possess medicinal values. This edible vegetable is known for its anti-inflammatory properties and has been studied for its bronchospasm preventive action. With the recent development in nanoformulations, this study was done to identify the effectiveness of MC nanoformulation in comparison to crude MC formulation in protecting animal from histamine-induced bronchospasm.
 Methods: The optimized MC nanoformulation was prepared with polyethylene glycol and soy phosphatidylcholine. The MC crude powder was prepared by drying in hot air oven and grinding in a blender. Eight guinea pigs of both sexes were given once daily MC nanoformulation per oral by mixing with water for 7 days. Evaluation of the formulation was done on the 2nd, 4th, and 6th h on day 1 and day 7 after administration of MC for protection in developing pre-convulsive dyspnea due to histamine-induced bronchospasm.
 Results: An analysis of variance test revealed statistically significant results in the protection of animals from developing bronchospasm after treatment with the MC nanoformulation in comparison to the control values. About 75% of animals were protected from developing bronchospasm on day 7 attributing to the cumulative effect of nanoformulation.
 Conclusion: The study proved that the MC nanoformulation could effectively prevent histamine-induced bronchospasm in guinea pigs.

Anti-anaphylactic and antiasthmatic activity of Euphorbia thymifolia L. on experimental animals

In Ayurveda, Euphorbia thymifolia L. (Euphorbiaceae) prescribed in the treatment of various ailments like bronchial asthma, cough, diarrhea and bleeding piles. The present study was investigated to evaluate antianaphylactic, mast cell stabilizing and antiasthmatic activity of methanol and aqueous extract of E. thymifolia (ET) on experimental animals. Anaphylaxis was induced by administration of horse serum and triple antigen vaccine intraperitoneal (i.p.) in albino Wistar rats. Extracts of ET were administered to the rats in dose of 250 and 500 mg/kg orally for 14 days. At the end of treatment, asthma score was measured and various blood parameters like differential count (DC), total WBC count and IgE were estimated. Interleukin (IL)-4, IL-5 and TNF-α were measured by ELISA commercial kit from BALF. Histopathological changes of lungs were observed. Antiasthmatic activity of extracts of ET was also studied on histamine-induced bronchospasm in guinea pigs. In vitro mast cell stabilizing activity of extracts was evaluated on compound 48/80 challenged rat intestinal mesenteric mast cells. The treatment with extracts of ET produced significant decrease in asthma score and they also brought to normalcy the increased total WBC, DC counts, serum IgE, TNF-α, IL-4 and IL-5 in BALF. The histopathological study further supported the protective effect of ET extracts. The pretreatment with extracts of ET displayed significant reduction in degranulation of mesenteric mast cell numbers. The treatment with extracts of ET significantly increased in time of PCD. Thus, these findings concluded that E. thymifolia could be effectively used in the treatment of anaphylaxis and asthma.

Amelioration of anaphylaxis, mast cell degranulation and bronchospasm by Euphorbia hirta L. extracts in experimental animals

The current investigation was aimed to assess anti-anaphylactic, mast cell stabilizing and anti-asthmatic activity of methanol and aqueous extract of Euphorbia hirta L. (Euphorbiaceae) on experimental animals. Anaphylaxis was induced by administration of horse serum and triple antigen vaccine subcutaneously in albino Wistar rats. Extracts of E. hirta (EH) were administered to the rats in dose of 250 and 500 mg/kg b.w. orally for 14 days. At the end of treatment, asthma score was measured and various blood parameters like differential count (DC), total WBC count and IgE were estimated. Interleukin (IL)-4, IL-5 and tumour necrosis factor (TNF)-α were measured by ELISA commercial kit from Broncho alveolar lavage fluid (BALF). Histopathological changes of lungs were observed. Anti-asthmatic activity of extracts of EH was also studied on histamine-induced bronchospasm in guinea pigs. In vitro mast cell stabilizing activity of extracts was evaluated on compound 48/80 challenged rat intestinal mesenteric mast cells. The treatment with extracts of EH produced significant decrease in asthma score and they also brought to normalcy the increased total WBC, DC counts, serum IgE, TNF-α, IL-4 and IL-5 in BALF. The histopathological study further supported the protective effect of EH extracts. The pre-treatment with extracts of EH displayed significant reduction in degranulation of mesenteric mast cell numbers. The treatment with extracts of EH significantly increased in time of pre-convulsive dyspnoea (PCD). Thus, these findings concluded that E. hirta could be effectively used in the treatment of anaphylaxis and asthma.

The effect of directly and indirectly acting sympathomimetic amines on bronchospasm in the guinea-pig during CO2 inhalation.

Abstract The bronchodilator effects of nine sympathomimetic amines were tested by reduction of histamine-induced bronchospasm in guinea-pigs. Their order of potency was: isoprenaline > adrenaline > noradrenaline > orciprenaline > ethylnoradrenaline > phenylephrine > amphetamine = tyramine > ephedrine. In guinea-pigs ventilated with 10% CO2 in air, there was a marked decrease in the bronchoconstrictor activity of histamine. Under these conditions, isoprenaline, adrenaline, noradrenaline and orciprenaline were as effective as bronchodilators as they had been in guinea-pigs ventilated with air, ethylnoradrenaline was less effective, phenylephrine, amphetamine and tyramine were completely inactive, and ephedrine potentiated the bronchoconstrictor action of histamine. After returning the guinea-pigs to ventilation with air, the bronchoconstrictor activity of histamine and the bronchodilator effects of the sympathomimetic amines were restored. The cardiovascular effects of histamine and of all the sympathomimetic amines used were diminished during ventilation with 10% CO2 in air and were restored after ventilation with air was resumed.

A comparative study of the spasmolytic activities of octaverine, perparine and papaverine.

Summary A comparative study has been made of the toxicities and spasmolytic activities of papaverine and 2 synthetic analogues, octaverine and perparine. Octaverine and perparine have about one-half of the acute toxicity of papaverine, as shown by the combined LD50 figures, the minimum convulsive doses and the minimum doses required to diminish reflexes and establish lateral decubitus in mice. Octaverine is 4 times, and perparine twice, as active as papaverine in suppressing the spontaneous contractions of rat uterus. All 3 alkaloids have the same activity against barium chloride-induced spasm in isolated guinea-pig ileum. Octaverine and papaverine possess the same activity against spasm provoked by histamine or by pilocarpine; perparine has one-half of the activity of papaverine against histamine spasm and double the activity of papaverine against pilocarpine spasm. 5 Orally administerd papaverine has no action against histamine-induced bronchospasm in guinea-pigs; both octaverine and perparine possess a definite although small activity under comparable conditions.

Inhibition of gastric acid secretion by a standardized aqueous extract of Cecropia glaziovii Sneth and underlying mechanism

Cecropia glazioui Sneth (Cecropiaceae) is used in folk medicine in tropical and subtropical Latin America as cardiotonic, diuretic, hypotensive, anti-inflammatory and anti-asthmatic. The hypotensive/antihypertensive activity of the plant aqueous extract (AE) and isolated butanolic fraction (BuF) has been confirmed and putatively related to calcium channels blockade in vascular smooth musculature [Lapa, A.J., Lima-Landman, M.T.R., Cysneiros, R.M, Borges, A.C.R., Souccar, C., Barreta, I.P., Lima, T.C.M., 1999. The Brazilian folk medicine program to validate medicinal plants - a topic in new antihypertensive drug research. In: Hostettman, K., Gupta, M.P., Marston, A. (Eds.), Proceedings Volume, IOCD/CYTED Symposium, Panamá City, Panamá, 23-26 February 1997. Chemistry, Biological and Pharmacological Properties of Medicinal Plants from the Americas. Harwood Academic Publishers, Amsterdam, pp. 185-196; Lima-Landman, M.T., Borges, A.C., Cysneiros, R.M., De Lima, T.C., Souccar, C., Lapa, A.J., 2007. Antihypertensive effect of a standardized aqueous extract of Cecropia glaziovii Sneth in rats: an in vivo approach to the hypotensive mechanism. Phytomedicine 14, 314-320]. Bronchodilation and antidepressant-like activities of both AE and BuF have been also shown [Delarcina, S., Lima-Landman, M.T., Souccar, C., Cysneiros, R.M., Tanae, M.M., Lapa, A.J., 2007. Inhibition of histamine-induced bronchospasm in guinea pigs treated with Cecropia glaziovi Sneth and correlation with the in vitro activity in tracheal muscles. Phytomedicine 14, 328-332; Rocha, F.F., Lima-Landman, M.T., Souccar, C., Tanae, M.M., De Lima, T.C., Lapa, A.J., 2007. Antidepressant-like effect of Cecropia glazioui Sneth and its constituents -in vivo and in vitro characterization of the underlying mechanism. Phytomedicine 14, 396-402]. This study reports the antiulcer and antisecretory gastric acid activities of the plant AE, its BuF and isolated compounds with the possible mechanism involved. Both AE and BuF were assayed on gastric acid secretion of pylorus-ligated mice, on acute models of gastric mucosal lesions, and on rabbit gastric H(+), K(+)-ATPase preparations. Intraduodenal injection of AE or BuF (0.5-2.0g/kg, i.d) produced a dose-related decrease of the basal gastric acid secretion in 4-h pylorus-ligated mice. At 1.0g/kg, BuF decreased the volume (28%) and total acidity (33%) of the basal acid secretion, and reversed the histamine (2.5mg/kg, s.c.)- or bethanecol (1.0mg/kg, s.c.)-induced acid secretion to basal values, indicating inhibition of the gastric proton pump. Pretreatment of mice with the BuF (0.05-0.5g/kg, p.o.) protected against gastric mucosal lesions induced by 75% ethanol, indomethacin (30mg/kg, s.c.) or restraint at 4 degrees C. BuF also decreased the gastric H(+), K(+)-ATPase activity in vitro proportionately to the concentration (IC(50)=58.8microg/ml). The compounds isolated from BuF, consisting mainly of cathechins, procyanidins and flavonoids [Tanae, M.M., Lima-Landman, M.T.R., De Lima, T.C.M., Souccar, C., Lapa, A.J., 2007. Chemical standardization of the aqueous extract of Cecropia glaziovii Sneth endowed with antihypertensive, bronchodilator, antacid secretion and antidepressant-like activities. Phytomedicine 14, 309-313], inhibited the in vitro gastric H(+), K(+)-ATPase activity at equieffective concentrations to that of BuF. The results indicate that C. glazioui constituents inhibit the gastric proton pump; this effect may account for the effective antisecretory and antiulcer activities of the standardized plant extract.

Inhibition of histamine-induced bronchospasm in guinea pigs treated with Cecropia glaziovi Sneth and correlation with the in vitro activity in tracheal muscles

A standardized aqueous extract (AE) and a purified fraction (BuF) of Cecropia glaziovi Sneth leaves were tested in unrestrained guinea pigs challenged with histamine. Changes of the respiratory pressure and rate were recorded in a whole body plethysmograph before and after treatment. The concentration of histamine necessary to produce bronchospasm was increased by five-fold following administration of AE (1.0 g/kg p.o.), and by two-fold after treatment with the semi-purified procyanidin/flavonoids enriched BuF (0.1 g/kg p.o.). Both effects were blocked by previous treatment with propranolol (10.0 mg/kg i.p.). In vitro incubation of BuF (0.1-1.0 mg/ml) decreased by 13-55% the maximal response of guinea pig tracheal muscle to histamine, without significant change of EC50. The results confirmed old reports on the useful pulmonary effects of Cecropia extracts. The bronchodilation observed in vivo seems to be related to beta-adrenergic activity observed in vitro only with high concentrations of the purified extract.

Discovery and preliminary pharmacology of Sch 37370, a dual antagonist of PAF and histamine

From a series of amide analogs of the histamine H1 antagonist, azatadine, a potent, orally active, dual platelet-activating factor (PAF) and histamine antagonist, Sch 37370, namely 1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo- [5,6]cyclohepta[1,2-b]pyridin-11-ylidine)piperidine, was discovered. Sch 37370 selectively inhibits PAF-induced aggregation of human platelets in vitro (IC50 = 0.6 microM), and in vivo inhibits PAF- and histamine-induced bronchospasm in guinea pigs with ED50 values of 6.0 and 2.4 mg/kg p.o., respectively. Sch 37370 is expected to be more efficacious than single mediator antagonists in allergic diseases, such as asthma.

Antiallergic activity of loratadine, a non‐sedating antihistamine

Loratadine is a new non-sedating antihistamine. The present studies compared loratadine and terfenadine, another non-sedating antihistamine, for their ability to inhibit the bronchial response to histamine and other autacoids which have been implicated as contributing to the symptoms of an allergic reaction. In addition, the two antihistamines were evaluated in models of immunologically mediated allergic reactions. Loratadine is a more potent inhibitor of histamine-induced bronchospasm in guinea pigs than is terfenadine. Both antihistamines exhibit marked antiserotonin activity at doses 10 times their antihistamine ED50 values. In contrast, loratadine and terfenadine produce little or no inhibition of the bronchial responses to methacholine, leukotriene C4 or platelet-activating factor. An allergic bronchospasm in guinea pigs is inhibited by loratadine (ED50 = 0.40 mg/kg, p.o.) and terfenadine (ED50 = 1.7 mg/kg, p.o.). The bronchospasm associated with allergic anaphylaxis in rats is significantly inhibited by 10 mg/kg, p.o. loratadine and 30 mg/kg, p.o. terfenadine. Loratadine exhibits antiallergy activity in vitro. At micromolar concentrations, loratadine inhibits the release of histamine from Con A and A23187-stimulated rat peritoneal mast cells and the release of histamine and leukotriene C4 from a Con A-stimulated cloned murine mast cell line.

Comparative pharmacology of arterenol, epinephrine and isopropylarterenol

A comarison has been made of the cardiovascular, bronchodilatory, spasmogenic, hyperglycemic, and adrenal-stimulating effects of arterenol, epinephrine, and isopropyluterenol in equivalent dose levels. Epinephrine is twice as potent as arterenol in producing vasoconstriction of the vascular bed of skeletal muscles. Epinephrine acts like arterenol to produce the vasopressor, and Like isopropylarterenol to produce the vasodepressor effect. Isopropylarterenol is three times more effective than epinephrine in prevention of histamine-induced bronchospasm in guinea pigs, while arterenol is 1/60 as effective as epinephrine. Arterenol, like epinephrine, causes contraction of isolated guinea pig's seminal vesicle, but is less active. Isopropylarterenol is devoid of a spasmogenic action. The hyperglycemic activity of arterenol is greater than that of isopropylarterenol, but less than that of epinephrine. They are equally influential on the ascorbic acid metabolism of the adrenals.