Effects of montelukast sodium on tendon healing: An experimental study

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Abstract

Introduction:

Montelukast sodium (MS) a selective leukotriene antagonist of the cysteinyl leukotriene receptor, has been used in the treatment of asthma and allergic rhinitis. In this study, we evaluated the effect of MS on the early inflammatory phase (histological) of nonsynovial tendon healing.

Materials and Methods:

Rats were divided randomly into two groups ( n = 6 each). MS (Singulair) was administered to one group at 10 mg/kg/day [250 g/day intraperitoneally (i.p.)]. The control group was administered 250 g/day of 0.9% saline i.p. This nonsynovial tendon was longitudinally divided at the midportion, cut transversely and then sutured. In both groups, the rats were sacrificed by decapitation 10 days later.

Results:

Decreased inflammatory cell infiltration and more properly oriented collagen fibres were observed in the MS group's histopathological specimens as compared to the control group's ( P < 0.05). Additionally, vascularity was decreased in the MS group.

Conclusion:

MS decreased tendon healing, apparently by inhibiting the early inflammatory phase of nonsynovial tendon healing.

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Most cited references 21

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Indomethacin and celecoxib impair rotator cuff tendon-to-bone healing.

John R Ehteshami, Scott A Rodeo, Justus B. Cohen … (2006)

Nonsteroidal anti-inflammatory drugs are commonly prescribed after rotator cuff repair. These agents can impair bone formation, but no studies have evaluated their impact on tendon-to-bone healing. Traditional nonselective nonsteroidal anti-inflammatory drugs and cyclooxygenase-2-specific nonsteroidal anti-inflammatory drugs interfere with tendon-to-bone healing. Controlled laboratory study. One hundred eighty Sprague-Dawley rats underwent acute rotator cuff repairs. Postoperatively, 60 rats received 14 days of celecoxib, a cyclooxygenase-2-specific nonsteroidal anti-inflammatory drug; 60 received indomethacin, a traditional nonselective nonsteroidal anti-inflammatory drug; and 60 received standard rat chow. Animals were sacrificed at 2, 4, and 8 weeks and evaluated by gross inspection, biomechanical testing, histologic analysis, and polarized light microscopy to quantify collagen formation and maturation. Five tendons completely failed to heal (4 celecoxib, 1 indomethacin). There were significantly lower failure loads in the celecoxib and indomethacin groups compared with the control groups at 2, 4, and 8 weeks (P < .001), with no significant difference between nonsteroidal anti-inflammatory drug groups. There were significant differences in collagen organization and maturation between the controls and both nonsteroidal anti-inflammatory drug groups at 4 and 8 weeks (P < .001). Controls demonstrated progressively increasing collagen organization during the course of the study (P < .001), whereas the nonsteroidal anti-inflammatory drug groups did not. Traditional and cyclooxygenase-2-specific nonsteroidal anti-inflammatory drugs significantly inhibited tendon-to-bone healing. This inhibition appears linked to cyclooxygenase-2. If the results of this study are verified in a larger animal model, the common practice of administering non-steroidal anti-inflammatory drugs after rotator cuff repair should be reconsidered.

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Randomized comparison of strategies for reducing treatment in mild persistent asthma.

Nicholas S. Peters, Mario Castro, Charles Irvin … (2007)

Treatment guidelines recommend the use of inhaled corticosteroids in patients with asthma who have persistent symptoms and the "stepping down" of therapy to the minimum needed to maintain control of asthma. Whether patients with asthma that is well controlled with the use of inhaled corticosteroids twice daily can receive a step-down treatment with once-daily montelukast (our primary hypothesis) or once-daily fluticasone propionate plus salmeterol (our secondary hypothesis) has not yet been determined. We randomly assigned 500 patients with asthma that was well controlled by inhaled fluticasone (100 microg twice daily) to receive continued fluticasone (100 microg twice daily) (169 patients), montelukast (5 or 10 mg each night) (166 patients), or fluticasone (100 microg) plus salmeterol (50 microg) each night (165 patients). Treatment was administered for 16 weeks in a double-blind manner. The primary outcome was the time to treatment failure. Approximately 20% of patients assigned to receive continued fluticasone or switched to treatment with fluticasone plus salmeterol had treatment failure, as compared with 30.3% of subjects switched to montelukast. The hazard ratio for both comparisons was 1.6 (95% confidence interval, 1.1 to 2.6; P=0.03). The percentage of days on which patients were free of asthma symptoms (78.7 to 85.8%) was similar across the three groups. Patients with asthma that is well controlled with the use of twice-daily inhaled fluticasone can be switched to once-daily fluticasone plus salmeterol without increased rates of treatment failure. A switch to montelukast results in an increased rate of treatment failure and decreased asthma control; however, patients taking montelukast remained free of symptoms on 78.7% of treatment days. (ClinicalTrials.gov number, NCT00156819 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.

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Inflammatory response of human tendon fibroblasts to cyclic mechanical stretching.

Guoguang Yang, Hongtao Wang, Savio Woo … (2004)

The cellular and molecular mechanisms for the development of tendinopathy are not clear, but inflammatory mediators produced by tendon fibroblasts in response to repetitive mechanical loading may be an important factor. (1) Cyclic stretching of tendon fibroblasts affects the production of leukotriene B(4) and the expression of 5-lipoxygenase; and (2) the production level of leukotriene B(4) is inversely related to that of prostaglandin E(2). Controlled laboratory study. Human patellar tendon fibroblasts were uniaxially stretched in the presence of indomethacin (25 micro M) or MK-886 (10 micro M). After stretching for 4 hours, followed by 4 hours rest, levels of prostaglandin E(2), leukotriene B(4), and expression of 5-lipoxygenase were measured. Stretched tendon fibroblasts increased the levels of leukotriene B(4) but did not appreciably change the expression of 5-lipoxygenase. Indomethacin decreased the cellular production of prostaglandin E(2) but caused increased leukotriene B(4) levels. MK-886 caused decreased production of leukotriene B(4) but increased production of prostaglandin E(2). Cyclic stretching of human tendon fibroblasts increases the production of prostaglandin E(2) and leukotriene B(4). Blocking prostaglandin E(2) production leads to increased leukotriene B(4) levels and vice versa. The use of nonsteroidal anti-inflammatory drugs for the treatment of tendon inflammation might increase the levels of leukotriene B(4) within the tendon, potentially contributing to the development of tendinopathy.

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Author and article information

Journal

Journal ID (nlm-ta): Indian J Orthop

Journal ID (iso-abbrev): Indian J Orthop

Journal ID (publisher-id): IJOrtho

Title: Indian Journal of Orthopaedics

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 0019-5413

ISSN (Electronic): 1998-3727

Publication date (Print): Sep-Oct 2013

Volume: 47

Issue: 5

Pages: 500-504

Affiliations

[1]Haydarpaşa Numune Research and Educational Hospital, İstanbul-Turkey

[1 ]Marmara University Medical Faculty, İstanbul-Turkey

Author notes

Address for correspondence: Dr. Atilla Polat, Haydarpaşa Numune Research and Educational Hospital, İstanbul/Turkey. E-mail: dr.atillapolat@ 123456hotmail.com

Article

Publisher ID: IJOrtho-47-500

DOI: 10.4103/0019-5413.118207

PMC ID: 3796924

PubMed ID: 24133311

SO-VID: e6e523ba-1356-40e7-9fe1-b73e0b8bee75

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Effects of montelukast sodium on tendon healing: An experimental study

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Abstract

Introduction:

Materials and Methods:

Results:

Conclusion:

Related collections

Orthopedics

Most cited references 21

Indomethacin and celecoxib impair rotator cuff tendon-to-bone healing.

Randomized comparison of strategies for reducing treatment in mild persistent asthma.

Inflammatory response of human tendon fibroblasts to cyclic mechanical stretching.

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