Effect of Lodoxamide on in vitro and in vivo Conjunctival Immediate Hypersensitivity Responses in Rats

Yanni, John M.; Weimer, Lori K.; Gläser, Regine; Lang, L S; Robertson, S.M.; Spellman, Joan M.

doi:10.1159/000236505

Cited by 32 publications

(19 citation statements)

References 12 publications

(13 reference statements)

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“…Güler et al [14]found lodoxamide more effective compared with sodium cromoglycate in the inhibition of vascular permeability in a passive allergy model of rabbits. Our study is in accordance with these two studies except for the level of efficacy of levacobastine reported in the first study [11]. That study differs with regard to the model tested.…”

Section: Discussionsupporting

confidence: 93%

“…This is why most of the studies evaluating the effectiveness of various substances on type I allergic reactions are focused on mast cells [6, 8, 9, 11]. Mast cells have been identified and described in the normal conjunctiva of rats and humans [12].…”

Section: Discussionmentioning

confidence: 99%

“…In the study by Yanni et al [11]which was performed with passive immunization of rats, the decrease in vascular permeability with lodoxamide was 43%, while sodium cromoglycate (2%) and levacobastine (0.05%) had no effect. Güler et al [14]found lodoxamide more effective compared with sodium cromoglycate in the inhibition of vascular permeability in a passive allergy model of rabbits.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of Antiallergic Drugs in an Experimental Model of Ocular Anaphylaxis

et al. 2003

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Purpose: To compare the efficacy of antiallergic drugs in an experimental ocular anaphylaxis model. Materials and Methods: Fifty-two rats were divided into 8 groups. Dithiothreitol and ovalbumin (OVA) were applied to both eyes of previously OVA-inoculated rats in groups 1–5 and 7. In groups 1–5, antiallergic efficacy of the drugs (lodoxamide, sodium cromoglycate, levacobastine, cimetidine, and diclofenac sodium) instilled on the right eyes were compared with the buffer instilled on the left eyes, measuring the amount of extravasated Evans blue (EB) dye by spectrophotometric analysis. Group 6 served as a control of EB dye extravasations in nonimmunized eyes. Histopathologic examinations for anaphylaxis and controls were done in groups 7 and 8. Results: Only levacobastine and lodoxamide decreased vascular permeability at a significant ratio (46%, p < 0.01 and 31%, p < 0.05, respectively). Conclusion: Levacobastine and lodoxamide but none of the three other drugs mentioned above were found to be effective in decreasing vascular permeability.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Comparison of Antiallergic Drugs in an Experimental Model of Ocular Anaphylaxis

et al. 2003

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“…4A, n = 4 experiments). Since lodoxamide is able to inhibit the release of rat mast cell mediators in vitro and in vivo [15, 16], and since rat mast cell-eosinophil interactions are required to induce antibody-dependent cell-mediated cytotoxicity [13], we have also investigated the role of lodoxamide in rat eosinophil-mediated antibody-dependent cell-mediated cytotoxicity. The results presented in figure 4B clearly indicate a dose-dependent inhibition of cytotoxicity, reaching more than 90% inhibition for the highest concentration of lodoxamide (p < 0.0001).…”

Section: Resultsmentioning

confidence: 99%

Inhibitory Effects of Lodoxamide on Eosinophil Activation

Capron

Loiseau

Papin

et al. 1998

Int Arch Allergy Immunol

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Recent reports describe the beneficial use of lodoxamide, an anti-allergic compound, for the treatment of asthma and allergic conjunctivitis. Lodoxamide is known as a mast cell stabilizer, however, the association of a significant clinical improvement with a specific decrease in eosinophil infiltrate suggested possible direct effects of lodoxamide on eosinophils. The chemotactic response of eosinophils to fMLP as well as to IL-5, in vitro, was very significantly and dose-dependently inhibited by Lodoxamide. Lodoxamide was also able to strongly inhibit the release of eosinophil peroxidase after IgA-dependent activation and, to a lesser extent, the release of eosinophil cationic protein and eosinophil-derived neurotoxin. Moreover, the release of cytotoxic mediators evaluated in an antibody-dependent cytotoxicity assay against parasitic targets was also significantly reduced, not only in the case of human eosinophils but also in a rat eosinophil-mast cell model of cytotoxicity. Taken together, these results indicate that lodoxamide can exert potent inhibitory effects on eosinophil activation in vitro combined with a strong inhibition of eosinophil attraction, leading therefore to a reduction in their pathological potential in vivo.

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“…IgE-mediated models of rat conjunctivitis used either direct or indirect sensitization and a large number of questions were answered with this species. Using ovalbumin-based protocols, it was shown that the rat models of allergic eye disease exhibit similar pharmacological properties as guinea-pig models concerning the effects of drugs such as lodoxamide, nedocromil, sodium cromoglycate, levacobastine, cimetidine, diclofenac sodium: (65, 72), or lodoxamide (73).…”

Section: Ratsmentioning

confidence: 99%

Animal models of allergic and inflammatory conjunctivitis

Groneberg

Bielory

Fischer

et al. 2003

Allergy

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Numerous recent reports have demonstrated an increase in the prevalence and incidence of allergic conditions during the past years which affect approximately 25% of the general population (1) and about US$ 6 billion alone are estimated as direct costs of allergic rhinoconjunctivitis (2). Whereas a large amount of studies have focused on the pathophysiology of allergic rhinitis and asthma over the past years, ocular allergies are less well studied. However, allergic diseases affecting the eye are very common (3) and pediatric studies have shown that within distinct cohorts, up to 32% of allergic children have an ocular allergy as the primary manifestation of allergy (4). Allergic eye diseases such as allergic conjunctivitis commonly present with the symptoms of itchy, watery, red, sore and swollen eyes, but not pain (5).In contrast to the large amount of experimental studies on allergic asthma and the detailed knowledge that exists on mediators of allergic airway inflammation (6-8), there are few experimental studies using models of allergic eye diseases. Detailed reviews to assess the pathophysiology and immunology of ocular allergies have been limited. This review hopefully fills this void to provide the clinical and translational researcher in the area of ocular allergy. Pathophysiology of ocular allergiesBefore characterizing the different animal models of ocular allergy which have been established so far, it is crucial to reflect that within the area of ocular allergies, different disease entities exist and that only some of them may be mimicked by animal models. Formally, conjunctivitis may be divided into allergic and nonallergic conjunctivitis and the allergic form may also be subdivided into IgE-mediated and non-IgE-mediated allergic conjunctivitis ( Fig. 1) (9). Clinically, the spectrum of conjunctivitis types can be subdivided into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis and giant papillary conjunctivitis.In contrast to the other forms of conjunctivitis, allergic conjunctivitis is commonly based on an IgEmediated hypersensitivity reaction. Furthermore, allergic Allergic eye diseases are complex inflammatory conditions of the conjunctiva with an increasing prevalence and incidence. The diseases are often concomitant with other allergic diseases such as allergic rhinitis, atopic dermatitis and allergic asthma. Despite the disabling and prominent symptoms of ocular allergies, they are less well studied and further insights into the molecular basics are still required. To establish new therapeutic approaches and assess immunological mechanisms, animal models of ocular allergies have been developed in the past years. The major forms of allergic ocular diseases, seasonal and perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis, each have different pathophysiological and immunological components. In contrast to these distinct entities, the current animal models are based on the sensitization against a small numbe...

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Effect of Lodoxamide on in vitro and in vivo Conjunctival Immediate Hypersensitivity Responses in Rats

Cited by 32 publications

References 12 publications

Comparison of Antiallergic Drugs in an Experimental Model of Ocular Anaphylaxis

Comparison of Antiallergic Drugs in an Experimental Model of Ocular Anaphylaxis

Inhibitory Effects of Lodoxamide on Eosinophil Activation

Animal models of allergic and inflammatory conjunctivitis

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