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At least 685 records · Page 38Linked to original sources
PubMed1994

Protective effects of papaverine salicylate in mouse ear dermatitis and PAF-induced rat paw oedema.

Papaverine salicylate (MR-800) has been tested as a topical antiinflammatory agent in several models of skin inflammation in rodents, such as mouse ear dermatitis induced by croton oil, cantharidin or zymosan, and rat paw oedema induced by PAF. MR-800 exerted a dose-dependent inhibitory activity in all assays, when equimolar doses of sodium salicylate or papaverine were less effective, suggesting the existence of a favourable synergism between salicylate and papaverine.

Animals↗
PubMed1980

Granuloma pouch assay. III. Enhancement of the carcinogenic effect of N-methyl-N'-nitro-N-nitrosoguanidine.

Proliferation of granulation tissue on the inside of a subcutaneous (s.c.) air pocket was induced in rats by administration of 0.5 ml of 0.25% croton oil (granuloma pouch). Two days after induction of the granuloma, i.e., during the period of maximal cell growth, a single dose of 0.6 mg or 0.1 mg N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered into the pouch. Fibrosarcomas of various histopathological types developed in 87% of the rats receiving the high dose and in 64% of the low dose animals. The mean latency period was 47.5 and 51.7 weeks respectively. Only one local sarcoma developed in rats treated with 0.6 mg MNNG by the s.c. route, and no tumors were observed in the groups treated with 0.1 mg s.c. The appearance of local sarcomas in the granuloma pouch tissue is correlated with previously reported frequency of point mutations (OUAR and HGPRT-) induced in granuloma fibroblasts with the same doses of MNNG. Possible mechanisms explaining the marked enhancement of the carcinogenic effect of MNNG in the granuloma pouch assay are discussed.

Animals↗
PubMed1998

Amentoflavone, a plant biflavone: a new potential anti-inflammatory agent.

Biflavonoid is one of unique classes of naturally-occurring bioflavonoids. Certain biflavonoids including amentoflavone were previously reported to have inhibitory effect on the group II phospholipase A2 activity. Amentoflavone was also found to inhibit cyclooxygenase from guinea-pig epidermis without affecting lipoxygenase. In this study, anti-inflammatory and analgesic activities of amentoflavone were evaluated. When amentoflavone was administered intraperitoneally, it showed a potent anti-inflammatory activity as determined by amelioration of croton-oil induced mouse ear edema. It also showed a potent anti-inflammatory activity in the rat carrageenan paw edema model (ED50 = 42 mg/kg) compared to the activity of prednisolone (35 mg/kg) and indomethacin (10 mg/kg). However, amentoflavone did not show a significant inhibitory activity against rat adjuvant-induced arthritis, a chronic inflammatory model. In addition, amentoflavone was found to possess a potent analgesic activity in the acetic acid writhing test (ED50 = 9.6 mg/kg) compared to the activity of indomethacin (3.8 mg/kg). These results suggest that amentoflavone may be a potential lead for a new type of anti-inflammatory agents having dual inhibitory activity of group II phospholipase A2 and cyclooxygenase.

Administration, Oral↗
PubMed1999

A novel approach to the discovery of non-systemic anti-inflammatory steroids; antedrug.

Therapeutic use of anti-inflammatory steroids is limited due primarily to their systemic suppressive effects on pituitary function and the immune system. To overcome the clinical limitation, a new approach toward the discovery of non-systemic anti-inflammatory steroids is based upon the antedrug concept introduced by this laboratory. The new concept describes locally active agents which are designed to undergo a predictable biotransformation to inactive metabolites upon entry into systemic circulation from the applied site. Thus, true antedrugs are devoid of systemic adverse effects. In a continuing effort, 16alpha-carboxylate and isoxazoline derivatives of prednisolone have been synthesized and screened. In the croton oil-induced ear edema bioassay, the following relative potencies were obtained setting hydrocortisone=1.0; 3a, 1.5; 3b, 3.1; 4a, 4.0; 4b, 12.2; 5b, 8.2; 6b, 11.2; 7a, 1.9; 7b, 4.1; 8a, 3.3; 8b, 6.8; 9a, 0.7; 9b, 8.6; 10a, 2.6; 10b, 7.4. Results of the five-day bioassay indicated that, in contrast to the parent compound, the novel steroidal antedrugs did not significantly alter body weight gain, thymus weights, adrenal weights or plasma corticosterone levels. Taken together, the antedrug concept appears to be a fundamentally sound strategy for the separation of local anti-inflammatory activity from systemic adverse effects.

Administration, Topical↗
PubMed2002

Effects of sophoraflavanone G, a prenylated flavonoid from Sophora flavescens, on cyclooxygenase-2 and in vivo inflammatory response.

Previously, several prenylated flavonoids having a C-8 lavandulyl moiety were found to inhibit cyclooxygenase-1 (COX-1) as well as 5-lipoxygenase (5-LOX), and sophoraflavanone G was the most potent inhibitor against these eicosanoid generating enzymes among 19 prenylated flavonoids tested. In this investigation, effects of sophoraflavanone G on COX-2 induction from RAW 264.7 cells and in vivo inflammatory response were studied. Sophoraflavanone G inhibited prostaglandin E2 (PGE2) production from lipopolysaccharide (LPS)-treated RAW cells by COX-2 down-regulation at 1-50 uM. Other prenylated flavonoids including kuraridin and sanggenon D also down-regulated COX-2 induction at 10-25 uM, while kurarinone and echinoisoflavanone did not. In addition, sophoraflavanone G showed in vivo anti-inflammatory activity against mouse croton oil-induced ear edema and rat carrageenan paw edema via oral (2-250 mg/kg) or topical administration (10-250 microg/ear). Although the potencies of inhibition were far less than that of a reference drug, prednisolone, this compound showed higher anti-inflammatory activity when applied topically, suggesting a potential use for several eicosanoid-related skin inflammation such as atopic dermatitis.

Animals↗
PubMed1998

Differential effects of inhibition of isoforms of cyclooxygenase (COX-1, COX-2) in chronic inflammation.

OBJECTIVE AND DESIGN: The anti-inflammatory effects of therapeutic dosing of drugs with greater selectivity for the inhibition of the constitutive (COX-1) or inducible isoform (COX-2) of cyclooxygenase were assessed in a model of chronic inflammation. METHODS: The murine chronic granulomatous tissue air pouch model involves the subcutaneous injection of air into the dorsum of mice followed 24 h later by the intrapouch injection of an inflammatory stimulus (0.5 ml of Freund's complete adjuvant containing 0.1% croton oil). Aspirin, more selective in vitro for the inhibition of COX-1 (10,200 (mg/kg) and nimesulide, a selective in vitro inhibitor of COX-2 (0.5, 5 mg/kg) were dosed p.o. daily from 3 days after injection of the inflammatory stimulus. Granuloma dry weight, vascularity and COX activity (measured as PGE2) were assessed at various time points throughout the inflammatory lesion to resolution at day 28. A second COX-2 inhibitor, NS 398 (0.1, 1, 10 mg/kg), was dosed p.o. daily from 3 days after the injection of the inflammatory stimulus and its effects on granuloma dry weight, vascularity and COX activity were measured at 7 days. RESULTS: Aspirin (200 mg/kg) significantly inhibited levels of PGE2 throughout the time course and at the lower dose (10 mg/kg) from day 14. Nimesulide (5 mg/kg) however, significantly increased levels of PGE2 at days 5 and 21, but at 0.5 mg/kg was without effect. Aspirin (200 mg/kg) significantly reduced granuloma dry weight at day 14 but had no effect on granuloma vascularity at day 7. In contrast, nimesulide (5 mg/kg) significantly increased granuloma vascularity at day 7 and granuloma dry weight at day 14. NS-398 at all doses had no effect on granuloma dry weight, vascularity or COX activity 7 days after the injection of the inflammatory stimulus. CONCLUSION: In this model of chronic inflammation, aspirin, more selective for the inhibition of COX-1 is more effective than the selective COX-2 inhibitors nimesulide and NS-398 at inhibiting granuloma dry weight, vascularity and COX activity.

Air↗
PubMed2001

Cholinergic transmission via central synapses in the locust nervous system.

In this study we examine the nature of chemical synaptic transmission between identified filiform hair receptors on the prothoracic segment of a locust and the identified postsynaptic projection interneuron (A4I1). The effects of pressure ejected acetylcholine, and various ligands of acetylcholine receptors on the activity of the postsynaptic neuron A4I1, or on wind-elicited responses in A4I1 are reported. It is suggested that the transmitter of the afferent fibers is acetylcholine, and that fast transmission is mediated by nicotinic acetylcholine-receptors. Both nicotine and carbachol act as agonists, whereas d-tubocurarine and alpha-bungarotoxin act as antagonists. The presence of muscarinic acetylcholine receptors was also evident from the modulatory effects of muscarine, oxotremorine and pilocarpine, which were blocked by bath application of atropine. GABA, and its agonists muscimol and cis-4-amino-crotonic-acid lead to inhibition of A4I1 responses. This inhibition was prevented by the additional application of picrotoxin. This suggests involvement of a ligand-gated GABA receptor which, most likely, increases chloride conductance. Metabotropic GABA-receptors do not seem to be involved, since baclofene, diazepam and bicuculline ejections had no effects. Glutamate also inhibits wind elicited A4I1 responses. Although attempts were made to further characterize the receptor involved, tested substances such as kainic acid, glycine, CNQX or GDEE had no effect.

Acetylcholine↗
PubMed1979

Interaction of benzo [A] pyrene and a hyperplastic agent in epidermal nuclear enlargement in the mouse. A dose response study.

Experiments were conducted on the effects of various dose levels of benzo [a]pyrene (BP) on nuclear size in mouse interfollicular epidermis over a 3-day period. Topical application of BP was made with or without croton oil (CO) (0.1 or 0.5%) in the vehicles acetone, toluene and methyl ethyl ketone (MEK). Nuclear size was measured on histological sections either manually or by Quantimet Image Analyser. Vehicle controls treated with 0.1 or 0.5% CO in acetone or MEK gave rise to epidermal hyperplasia with some nuclear enlargement and toluene without CO produced a similar response. It was found that when BP was applied in a vehicle capable of inducing hyperplasia, the nuclear enlargement produced was greater than that produced by either the vehicle control or BP in a non-irritant vehicle. The enhancement of response to BP when tested in the presence of a hyperplastic agent resulted in lower concentrations of BP being detectable. As the levels of BP detectable by nuclear enlargement under these conditions compared reasonably well with those detectable in long-term tests, this system might be usable as a basis for a short-term test for carcinogens.

Animals↗
PubMed1987

Covalent binding of proteins to grafted plastic surfaces suitable for immunoassays. I. Binding capacity and characteristics of grafted polymers.

A method for the introduction of chemically reactive groups onto polymeric surfaces, suitable for immunoassays, is described. The method, referred to as grafting, uses gamma irradiation from a 60Co source to initiate the free radical reaction. Polystyrene and polyvinyl chloride surfaces were grafted with crotonic acid and characterized with ESCA. 2 nmol/cm2 of carboxylic groups were added during the method. Increased hydrophilic properties of the carboxylated surfaces were recorded by contact angle measurements. The grafting reaction did not impair the optical quality of the polymers studied. Various proteins were covalently linked to the modified surfaces of microtiter plates and tubes by means of a water-soluble carbodiimide. A significantly enhanced total capacity and strength of binding to grafted surfaces was demonstrated as compared to passive adsorption of the proteins to untreated surfaces.

Animals↗
PubMed1987

Structure-activity relationships of a series of novel topical corticosteroids.

The effect of various heteroaroyl groups in the 17-position of topical corticosteroids has been studied. The corticosteroids esterified at C17 were of 9 alpha,11 beta-dichloro, 9 alpha-chloro 11 beta-hydroxy and 9 alpha-fluoro 11 beta-hydroxy series. Among the 17-acyl groups 2'-furoates were most extensively investigated, although 2'-thenoates, 3'-thenoates and 3'-furoates were also examined. Many of these esters exhibited enhanced topical anti-inflammatory potencies. The most potent compounds investigated were the 21-chloro 17(2'-furoates) either in the 9 alpha,11 beta-dichloro, or in the 9 alpha-chloro 11 beta-hydroxy series. These compounds were at least 6 times as potent as betamethasone 17-valerate. Among 16-substituents studied 16 alpha-methyl compounds had the highest potency. Topical anti-inflammatory potencies were determined by using a 5-day modification of the croton oil ear assay in mice. The more potent compounds were also evaluated in the P. ovale induced chronic psoriaform lesion in the guinea-pig.

Administration, Topical↗
PubMed1986

Calcium-independent induction of cytocidal activity of polymorphonuclear leukocytes by phorbol myristate acetate-like tumor promoters.

Tumor promoters were tested for the ability to induce cytocidal activity of polymorphonuclear leukocytes (PMNs), and the extracellular calcium-dependency of their PMN cytotoxicities were examined in comparison with that by some immunomodulators. Immunomodulators such as linear beta-1, 3-D-glucan (TAK) induced potent cytocidal activity of PMNs. The induction was dependent on extracellular Ca2+. Tumor promoters such as phorbol 12-myristate 13-acetate (PMA) and its derivatives, teleocidin which is structurally unrelated to PMA, and croton oil as an example of mixture also induced potent PMN cytotoxicities. In the latter cases, however, the induction was not dependent on extracellular Ca2+. The ability of these tumor promoters to induce PMN cytotoxicity correlated well with their skin-tumor promoting activities. These results indicate that inductions by PMA-like tumor promoters are distinguishable from those by TAK-like immunomodulators in not being Ca2+-dependent. The application of Ca2+-independent PMN cytotoxicity to detect PMA-like tumor promoters is discussed.

Animals↗
PubMed1994

Effects of CGRP in different models of mouse ear inflammation.

The anti-inflammatory activity of calcitonin gene-related peptide (CGRP) has been studied in cutaneous inflammation induced by croton oil (CO), arachidonic acid (AA), tetradecanoylphorbol acetate (TPA) or cantharidin (CA). Our results show that mouse ear inflammation induced by CO, AA or TPA is decreased by topical administration of CGRP, whereas that induced by CA is not affected. The dose-response and temporal analysis of CGRP effect show that the maximal activity is present at the dose of 30 pmol/ear and when administered 30 min after the irritating agent. Moreover, pretreatment with capsaicin is able to mimic the anti-inflammatory effect of exogenous CGRP, while simultaneous administration of CGRP and capsaicin produces a reduced response. Our results suggest that CGRP released from sensory.

Analysis of Variance↗
PubMed1977

Effects of the water-soluble carcinogen 4-nitroquinoline N-oxide on hamster lingual mucosa.

The water-soluble carcinogen 4-nitroquinoline N-oxide (4NQO) was painted onto hamster ventral lingual mucosa twice weekly for up to 20 weeks. No neoplasms developed during this period. The promoting agent croton oil was applied to the treated areas in an attempt to determine whether initiation had occurred. During the following 6 months, one animal developed a papilloma and three animals showed areas of epithelial atypia in the treated mucosa. No malignant neoplasms were seen. Despite its efficiency in producing intraoral neoplasms in the rat, 4NQO would appear to be a poor choice in the hamster.

4-Nitroquinoline-1-oxide↗
PubMed1995

Steroidal anti-inflammatory antedrugs: synthesis and pharmacological evaluation of 16 alpha-alkoxycarbonyl-17-deoxyprednisolone derivatives.

In a continuing effort to minimize the systemic adverse effects of potent anti-inflammatory steroids, a series of 16 alpha-alkoxycarbonyl-17-deoxyprednisolone derivatives: methyl (8a), ethyl (8b), isopropyl (8c), and benzyl (8d) 11 beta,21-dihydroxy-3,20-dioxo-1,4-pregnadiene-16 alpha-carboxylate, was synthesized and evaluated for their topical and local anti-inflammatory activities. In the acute croton oil-induced ear edema dose-response bioassay, the topical anti-inflammatory potencies of these esters relative to prednisolone, 1, were: 8a:1.0, 8b:1.3, 8c:4.0, 8a:4.7 and 1:1.0. The putative metabolite, 11 beta,21-dihydroxy-3,20-dioxo-1,4-pregnadiene-16 alpha-carboxylic acid, 7, was inactive in this test. A seven day cotton pellet granuloma bioassay was employed to study the local and systemic anti-inflammatory activities of these steroids. The local anti-inflammatory potencies of these esters relative to prednisolone, 1, were 1.3, 1.5, 2.3, 2.5, and 1.0 for 8a, 8b, 8c, 8d, and 1, respectively. In this semi-chronic study, only prednisolone exhibited significant untoward side effects, such as reduction in thymus weights, normal body weight gain, and normal plasma corticosterone levels. The increase in the topical and local potencies of these steroid esters was consistent with the increase in their 1-octanol/buffer partition coefficient. The ratio of local to systemic anti-inflammatory activity of 8c and 8d was four times that of prednisolone. The effects of increasing the size of the alkoxy group of these new steroids on both topical and local anti-inflammatory activity and their concomitant decrease in untoward systemic effects were unequivocally demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1992

Synthesis, characterization, and antiinflammatory activity of naproxen complexes with rare earth (III).

RE(III) complexes of Naproxen(HNap) have been synthesized and characterized by elemental analyses, conductance measurements, solubilities, thermal analysis, infrared, proton magnetic resonance, and electronic spectral data. The elemental analyses reveal the presence of 1:3 (metal:ligand) stoichiometry and the IR spectra suggest the carboxylate group of HNap functions, as a bridging ligand to coordinate to RE(III) ions. The electronic spectra recorded in solid exhibit only slight shifts in visible regions, on which beta, delta and b1/2 of covalent parameters have been calculated. Formalin-induced rat paw edema and croton oil-induced rat ear edema inflammatory models were chosen to examine the antiinflammatory activity of Nd(III) complex, which ascertained enhanced antiinflammatory activity relative to the ligand.

Animals↗
PubMedDate not supplied

Effect of aristolochic acid on arachidonic acid cascade and in vivo models of inflammation.

Recently, it has been reported that aristolochic acid inhibits phospholipase A2 (PLA2) in vitro and also decrease either oedema induced by snake venom and human synovial fluid PLA2. The aim of this research was to study the antiinflammatory activity of aristolochic acid and to investigate the effect of the alkaloid on the enzymes involved in the release of eicosanoids. Our results demonstrate that aristolochic acid is able to inhibit inflammation induced by immunological, immune complexes, and nonimmunological agents such as carrageenan or croton oil. We suggest that one mechanism of the antiinflammatory activity of alkaloid may be by directly blocking PLA2 catalyzed release of arachidonic acid. Moreover, this study demonstrates that aristolochic acid could also inhibit other steps involved in eicosanoids release such as cyclooxygenase and lipooxygenase pathways.

Administration, Topical↗
PubMed1982

Isolation and purification of rat acute-phase alpha 2-macroglobulin.

Acute-phase alpha 2-macroglobulin was highly purified from the serum of rats in which this protein had been induced 48 h previously by the injection of croton oil, an inflammatory agent. The isolation protocol involved two non-denaturing steps; first, separation according to molecular weight by gel filtration on Ultrogel AcA 22 and second, negative affinity chromatography which bound contaminating proteins to the column while allowing acute-phase alpha 2-macroglobulin to pass through. Several criteria were used to assess the purity of acute-phase alpha 2-macroglobulin, after which the protein by mass determination and by two different protein assays. Pure rat acute-phase alpha 2-macroglobulin was used to produce a monospecific antiserum and to calibrate a secondary standard of rat acute-phase serum by developing and characterizing rocket immunoelectrophoresis assay.

Animals↗