Startseite Medizin Pioglitazone attenuate level of myeloperoxidases and nitic oxide in psoriatic lesion: a proof-of-concept study in a imiquimod induced psoriasis model in rat
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Pioglitazone attenuate level of myeloperoxidases and nitic oxide in psoriatic lesion: a proof-of-concept study in a imiquimod induced psoriasis model in rat

  • Oishani Chatterjee und Debjeet Sur ORCID logo EMAIL logo
Veröffentlicht/Copyright: 12. Februar 2024

Abstract

Objectives

Psoriasis is a persistent autoimmune inflammatory condition that is primarily affecting the skin. Pioglitazone (PGZ), a peroxisome proliferator activated receptor gamma (PPARγ) agonist, has been reported to have anti-inflammatory effects. However, the role of PGZ in psoriatic disease remains unclear. In this study, we aimed to repurpose the use of the PGZ for the treatment of psoriasis.

Methods

To investigate its efficacy, we employed an imiquimod (IMQ)-induced rat model. Wistar rats are randomly allocated to four different groups. Group, I served as a negative control, Group II IMQ control, Group III was treated with pioglitazone hydrogel and Group IV received standard drug betamethasone cream. PASI score was monitored on every alternative day and on day 7 animals were sacrificed and histopathology of skin was performed. Level of nitric oxide (NO) and myeloperoxidase (MPO) was also performed using established methods.

Results

The results of the experiment revealed that treatment with PGZ significantly (p<0.05) reduced redness, scaling, and skin thickening, surpassing the effectiveness of standard drugs. Our result also indicates that PGZ significantly (p<0.05) inhibits the release of both MPO and NO from the psoriatic lesions.

Conclusions

PGZ effectively reduces the severity of psoriasis possibly by inhibiting the accumulation of neutrophil at the psoriatic area which indirectly regulates the release of NO in the affected area. Our study showed we can repurpose the PGZ for the management of psoriasis.


Corresponding author: Dr. Debjeet Sur, Division of Pharmacology, Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F Nilgunj Road, Panihati, Kolkata, West Bengal, 700114, India, E-mail:

Acknowledgments

The Director and Principal of Guru Nanak Institute of Pharmaceutical Science and Technology, Kolkata, India, and the management of JIS Group, Kolkata India are highly acknowledged for encouragement and support.

  1. Research ethics: All the experimental procedures and protocols were reviewed and approved by the Institutional Animal Ethical Committee (CCSEA approval no. GNIPST/IAEC/s/2023/DS-02).

  2. Informed consent: Not applicable.

  3. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: The authors state no conflict of interest.

  5. Research funding: None declared.

  6. Data availability: Enquiries about data availability should be directed to the authors.

References

1. Griffiths, CEM, Armstrong, AW, Gudjonsson, JE, Barker, JNWN. The Lancet. Psoriasis 2021;397:1301–15. https://doi.org/10.1016/s0140-6736(20)32549-6.Suche in Google Scholar PubMed

2. Rendon, A, Schäkel, K. Psoriasis pathogenesis and treatment. Int J Mol Sci 2019;20:1475. https://doi.org/10.3390/ijms20061475.Suche in Google Scholar PubMed PubMed Central

3. Tokuyama, M, Mabuchi, T. New treatment addressing the pathogenesis of psoriasis. Int J Mol Sci 2020;21:1–16. https://doi.org/10.3390/ijms21207488.Suche in Google Scholar PubMed PubMed Central

4. Wong, T, Hsu, L, Liao, W. Phototherapy in psoriasis: a review of mechanisms of action. J Cutaneous Med Surg 2016;17:6–12.10.2310/7750.2012.11124Suche in Google Scholar PubMed PubMed Central

5. Lowes, MA, Bowcock, AM, Krueger, JG. Pathogenesis and therapy of psoriasis. Nature 2007;445:866–73. https://doi.org/10.1038/nature05663.Suche in Google Scholar PubMed

6. Sobolev, V, Nesterova, A, Soboleva, A, Mezentsev, A, Dvoriankova, E, Piruzyan, A, et al.. Analysis of PPARγ signaling activity in psoriasis. Int J Mol Sci 2021;22:8603. https://doi.org/10.3390/ijms22168603.Suche in Google Scholar PubMed PubMed Central

7. Malhotra, S, Bansal, D, Shafiq, N, Pandhi, P, Kumar, B. Potential therapeutic role of peroxisome proliferator activated receptor-γ agonists in psoriasis. Expert Opin Pharmacother 2005;6:1455–61. https://doi.org/10.1517/14656566.6.9.1455.Suche in Google Scholar PubMed

8. Haskamp, S, Bruns, H, Hahn, M, Hoffmann, M, Gregor, A, Löhr, S, et al.. Myeloperoxidase modulates inflammation in generalized pustular psoriasis and additional rare pustular skin diseases. Am J Hum Genet 2020;107:527–38. https://doi.org/10.1016/j.ajhg.2020.07.001.Suche in Google Scholar PubMed PubMed Central

9. Coleman, JW. Nitric oxide in immunity and inflammation. Int Immunopharmacol 2001;1:1397–406. https://doi.org/10.1016/s1567-5769(01)00086-8.Suche in Google Scholar PubMed

10. Greaves, MW, Weinstein, GD. Treatment of psoriasis. N Engl J Med 1995;332:581–9.10.1056/NEJM199503023320907Suche in Google Scholar PubMed

11. Lian, J, Fu, J. Pioglitazone for NAFLD patients with prediabetes or type 2 diabetes mellitus: a meta-analysis. Front Endocrinol 2021;12:615409. https://doi.org/10.3389/fendo.2021.615409.Suche in Google Scholar PubMed PubMed Central

12. Ishibashi, M, Egashira, K, Hiasa, K, Inoue, S, Ni, W, Zhao, Q, et al.. Antiinflammatory and antiarteriosclerotic effects of pioglitazone. Hypertension 2002;40:687–93. https://doi.org/10.1161/01.hyp.0000036396.64769.c2.Suche in Google Scholar PubMed

13. Mittal, R, Malhotra, S, Pandhi, P, Kaur, I, Dogra, S. Efficacy and safety of combination acitretin and pioglitazone therapy in patients with moderate to severe chronic plaque-type psoriasis: a randomized, double-blind, placebo-controlled clinical trial. Arch Dermatol 2009;145:387–93. https://doi.org/10.1001/archdermatol.2009.5.Suche in Google Scholar PubMed

14. Zhang, JZ, Ding, Y, Xiang, F, Yu, SR, Zhang, DZ, Guan, MM, et al.. Effectiveness and safety of different doses of pioglitazone in psoriasis: a meta-Analysis of randomized controlled trials. Chin Med J (Engl) 2020;133:444–51. https://doi.org/10.1097/cm9.0000000000000642.Suche in Google Scholar PubMed PubMed Central

15. Ellis, CN, Varani, J, Fisher, GJ, Zeigler, ME, Pershadsingh, HA, Benson, SC, et al.. Troglitazone improves psoriasis and normalizes models of proliferative skin disease: ligands for peroxisome proliferator-activated receptor-γ inhibit keratinocyte proliferation. Arch Dermatol 2000;136:609–16. https://doi.org/10.1001/archderm.136.5.609.Suche in Google Scholar PubMed

16. Swanson, CR, Joers, V, Bondarenko, V, Brunner, K, Simmons, HA, Ziegler, TE, et al.. The PPAR-γ agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys. J Neuroinflammation 2011;8:91. https://doi.org/10.1186/1742-2094-8-91.Suche in Google Scholar PubMed PubMed Central

17. Ito, H, Ando, T, Ogiso, H, Arioka, Y, Seishima, M. Inhibition of induced nitric oxide synthase enhances the anti-tumor effects on cancer immunotherapy using TLR7 agonist in mice. Cancer Immunol Immunother 2015;64:429–36. https://doi.org/10.1007/s00262-014-1644-6.Suche in Google Scholar PubMed PubMed Central

18. Sweeney, CM, Tobin, AM, Kirby, B. Innate immunity in the pathogenesis of psoriasis. Arch Dermatol Res 2011;303:691–705. https://doi.org/10.1007/s00403-011-1169-1.Suche in Google Scholar PubMed

19. Schoonjans, K, Staels, B, Auwerx, J. Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 1996;37:907–25. https://doi.org/10.1016/s0022-2275(20)42003-6.Suche in Google Scholar

20. Toobian, D, Ghosh, P, Katkar, GD. Parsing the role of PPARs in macrophage processes. Front Immunol 2021;12:783780. https://doi.org/10.3389/fimmu.2021.783780.Suche in Google Scholar PubMed PubMed Central

21. Cinelli, MA, Do, HT, Miley, GP, Silverman, RB. Inducible nitric oxide synthase: regulation, structure, and inhibition. Med Res Rev 2020;40:158.10.1002/med.21599Suche in Google Scholar PubMed PubMed Central

22. Briganti, S, Picardo, M. Antioxidant activity, lipid peroxidation and skin diseases. What’s new. J Eur Acad Dermatol Venereol 2003;17:663–9. https://doi.org/10.1046/j.1468-3083.2003.00751.x Suche in Google Scholar PubMed

23. Tai, Y, Wang, Q, Korner, H, Zhang, L, Wei, W. Molecular mechanisms of T cells activation by dendritic cells in autoimmune diseases. Front Pharmacol 2018;9:360499. https://doi.org/10.3389/fphar.2018.00642.Suche in Google Scholar PubMed PubMed Central

24. Kuenzli, S, Saurat, JH. Peroxisome proliferator‐activated receptors in cutaneous biology. Br J Dermatol 2003;149:229–36.10.1046/j.1365-2133.2003.05532.xSuche in Google Scholar PubMed

25. Sobolev, V, Nesterova, A, Soboleva, A, Mezentsev, A, Dvoriankova, E, Piruzyan, A, et al. Analysis of PPARγ signaling activity in psoriasis. Int J Mol Sci 2021;22:8603. https://doi.org/10.3390/ijms22168603.Suche in Google Scholar PubMed PubMed Central

26. d’Angelo, M, Castelli, V, Catanesi, M, Antonosante, A, Dominguez-Benot, R, Ippoliti, R, et al.. PPARγ and cognitive performance. Int J Mol Sci 2019;20:5068. https://doi.org/10.3390/ijms20205068.Suche in Google Scholar PubMed PubMed Central

27. Villapol, S. Roles of peroxisome proliferator-activated receptor-gamma on brain and peripheral inflammation. Cell Mol Neurobiol 2018;38:121. https://doi.org/10.1007/s10571-017-0554-5.Suche in Google Scholar PubMed PubMed Central

28. Nada, H, Abo-Elmaged, R, Fahmy, H, Mahmoud, A. Estimation of nitric oxide level in psoriatic patients and its correlation with disease severity. Egypt J Dermatol Venerology 2013;33:71. https://doi.org/10.4103/1110-6530.123952.Suche in Google Scholar

29. Cals-Grierson, MM, Ormerod, AD. Nitric oxide function in the skin. Nitric Oxide 2004;10:179–93. https://doi.org/10.1016/j.niox.2004.04.005.Suche in Google Scholar PubMed

Received: 2023-12-09
Accepted: 2024-01-26
Published Online: 2024-02-12

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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