The mast cell stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures

Monument, Michael J.; Hart, David A.; Befus, A. Dean; Salo, Paul; Zhang, Mei; Hildebrand, Kevin A.

doi:10.1007/s00011-011-0409-3

Cited by 57 publications

(70 citation statements)

References 35 publications

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“…Given such pharmacological properties of ketotifen, the administration of this drug could also be useful in the treatment of organ fibrosis in addition to its primary efficacy for allergic diseases. Recently, several animal studies have actually shown the therapeutic efficacy of ketotifen in the treatment of post-traumatic dermal or joint capsular fibrosis [58,59].…”

Section: Discussionmentioning

confidence: 99%

Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

Baba

Tachi²,

Ejima³

et al. 2016

Cell Physiol Biochem

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Background: Anti-allergic drugs, such as tranilast and ketotifen, inhibit the release of chemokines from mast cells. However, we know little about their direct effects on the exocytotic process of mast cells. Since exocytosis in mast cells can be monitored electrophysiologically by changes in the whole-cell membrane capacitance (Cm), the absence of such changes by these drugs indicates their mast cell-stabilizing properties. Methods: Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of tranilast and ketotifen on the Cm during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Relatively lower concentrations of tranilast (100, 250 µM) and ketotifen (1, 10 µM) did not significantly affect the GTP-γ-S-induced increase in the Cm. However, higher concentrations of tranilast (500 µM, 1 mM) and ketotifen (50, 100 µM) almost totally suppressed the increase in the Cm, and washed out the trapping of the dye on the surface of the mast cells. Compared to tranilast, ketotifen required much lower doses to similarly inhibit the degranulation of mast cells or the increase in the Cm. Conclusions: This study provides electrophysiological evidence for the first time that tranilast and ketotifen dose-dependently inhibit the process of exocytosis, and that ketotifen is more potent than tranilast in stabilizing mast cells. The mast cell-stabilizing properties of these drugs may be attributed to their ability to counteract the plasma membrane deformation in degranulating mast cells.

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Section: Discussionmentioning

confidence: 99%

Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

Baba

Tachi²,

Ejima³

et al. 2016

Cell Physiol Biochem

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“…Analysis of cardiac and peritoneal HO revealed presence of mast cells near sites of ectopic bone formation [41, 63]. Mast cells have also been shown to directly induce fibrosis following biomaterial scaffold implants in mice, indicating a more universal role of these cells in the overall wound repair process [56, 64, 65]. …”

Section: Innate Immunity and Heterotopic Ossificationmentioning

confidence: 99%

The Immunological Contribution to Heterotopic Ossification Disorders

Convente

Wang

Pignolo

et al. 2015

Curr Osteoporos Rep

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The formation of bone outside the endogenous skeleton is a significant clinical event, rendering affected individuals with immobility and a diminished quality of life. This bone, termed heterotopic ossification (HO), can appear in patients following invasive surgeries and traumatic injuries, as well as progressively manifest in several congenital disorders. A unifying feature of both genetic and non-genetic episodes of HO is immune system involvement at the early stages of disease. Activation of the immune system sets the stage for the downstream anabolic events that eventually result in ectopic bone formation, rendering the immune system a particularly appealing site of early therapeutic intervention for optimal management of disease. In this review we will discuss the immunological contributions to HO disorders, with specific focus on contributing cell types, signaling pathways, relevant in vivo animal models, and potential therapeutic targets.

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“…Also, body weight, diseases. Interestingly, it has been applied to non-allergic diseases, like improving sperm quality [10], irritable bowel syndrome [11] and reducing joint capsule fibrosis [12]. In addition, it has been suggested ketotifen has a novel medication for diabetes through stabilization of mast cells in animal model and human [13,14].…”

Section: Effect Of Ketotifen On Body Weight and Glucose Metabolismmentioning

confidence: 99%

Role of Ketotifen on metabolic profiles, inflammation and oxidative stress in diabetic rats

et al. 2017

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Abstract. We aim to explore effects of Ketotifen on metabolic profiles, inflammation and oxidative stress. Sprague Dawley (SD) male rats were randomly divided into normal control group (NC) and experimental groups, and experimental group rats were fed with high-sugar and fat diet for 6 weeks. Then, experimental group rats were divided into diabetes group (DM) and ketotifen treatment group (KT). KT group was given ketotifen via Intragastric for 8 weeks with the dosage of 0.09 mg/kg/d. Fasting plasma glucose (FPG) was measured using glucose oxidase-phenol amino phenazone method. Fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were tested by enzyme-linked immunosorbent assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) were quantified by spectrophotometer method. Before Ketotifen administration, compared with NC group, DM and KT groups showed significantly high levels of body weight,

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The mast cell stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures

Abstract: These data suggest an inflammatory pathway mediated by mast cell activation is involved in joint capsule fibrosis after traumatic injury.

Cited by 57 publications

References 35 publications

Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

The Immunological Contribution to Heterotopic Ossification Disorders

Role of Ketotifen on metabolic profiles, inflammation and oxidative stress in diabetic rats

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