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Montelukast potentiates the antiinflammatory effect of NSAIDs in the rat paw formalin model and simultaneously minimizes the risk of gastric damage

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Abstract

Objective and design

Montelukast, a cysteinyl leukotriene receptor antagonist, exhibits antiinflammatory action. We tested whether exposure to montelukast plus nonsteroidal antiinflammatory drugs (NSAIDs) elicits better control of paw inflammation in the rat formalin test and improves associated gastric damage.

Materials

A total of 46 adult male rats were used in the study.

Treatments

We evaluated separate and combined effects of montelukast (20 mg/kg), celecoxib (COX2 inhibitor, 10 mg/kg), and diclofenac (nonselective COX1/COX2 inhibitor, 10 mg/kg) on paw and gastric damage in the rat formalin test.

Results

Individual pretreatments of rats with montelukast, diclofenac, or celecoxib partly reduced formalin-induced increases in (i) paw edema, fibrosis, and inflammatory cells, (iii) serum interleukin-6 (IL-6) and leukotrienes (LTB4 and LTD4), and (iv) paw expressions of inducible nitric oxide synthase (iNOS) and COX2. These effects were accentuated in rats treated with montelukast plus diclofenac or montelukast plus celecoxib. Alternatively, montelukast or celecoxib, but not diclofenac, alleviated formalin-evoked gastric damage and increments in tumor necrosis factor-α and decrements in prostaglandin-E2. These advantageous gastric influences were potentiated in rats treated with montelukast plus celecoxib.

Conclusions

While montelukast equally enhances antiinflammatory action of diclofenac or celecoxib via downregulating iNOS/COX2/LTs/IL-6 signaling, its gastroprotective action is preferentially potentiated by celecoxib.

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Acknowledgements

The authors are grateful to Dr. Marwa M. Essawy, Oral Pathology Department, Faculty of Dentistry, Alexandria University, Egypt, for helping with the morphometric studies. We also thank the following 2019 Senior Pharmacy Students, Pharos University in Alexandria, Alexandria, Egypt, for their help during the experiments: Mohamed Y. Mohamed, Noran M. Tarek, Omnia E. Ibrahim, Mohamed S. Gouda, Mahmoud K. Elhalougy, Mohamed A. Mohamed, Mohamed M. Gamil, Mamoud K. Eldeeb, Basem Abdelmaseeh, Eman M. Abdelaziz.

Funding

No funds, grants, or other support was received.

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Author notes

  1. Sherien A. Abdelhady and Mennatallah A. Ali contributed equally to the work.

Authors and Affiliations

  1. Faculty of Pharmacy, Department of Pharmacology and Therapeutics, Pharos University in Alexandria, Alexandria, Egypt

    Sherien A. Abdelhady & Mennatallah A. Ali

  2. Faculty of Dentistry, Department of Basic Sciences, Pharos University in Alexandria, Alexandria, Egypt

    Tamer A. Al-Shafie & Ebtsam M. Abdelmawgoud

  3. Faculty of Medicine, Department of Clinical Pharmacology, Alexandria University, Alexandria, Egypt

    Dalia M. Yacout

  4. Faculty of Pharmacy, Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt

    Mahmoud M. El-Mas

  5. Faculty of Medicine, Department of Pharmacology and Toxicology, Kuwait University, Safat, PO Box 24923, 13110, Kuwait City, Kuwait

    Mahmoud M. El-Mas

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  1. Sherien A. Abdelhady
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  2. Mennatallah A. Ali
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  3. Tamer A. Al-Shafie
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Correspondence to Mahmoud M. El-Mas.

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All animal experiments were conducted in compliance with institutional guidelines on the care and use of laboratory animals and with the guidelines of the National Institutes of Health guide for the care and use of laboratory animals (NIH Publications No. 8023, revised 1978) [18] and the Egyptian guide for the care and use of laboratory animals [19]. All efforts were made to limit the suffering of rats during the experimental period. This article does not contain any studies with human participants performed by any of the authors.

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Abdelhady, S.A., Ali, M.A., Al-Shafie, T.A. et al. Montelukast potentiates the antiinflammatory effect of NSAIDs in the rat paw formalin model and simultaneously minimizes the risk of gastric damage. Inflamm. Res. 70, 981–992 (2021). https://doi.org/10.1007/s00011-021-01492-9

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  • DOI: https://doi.org/10.1007/s00011-021-01492-9

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