ANTI-INFLAMMATORY EFFICACY OF NSAIDS AND THEIR COMBINATIONS WITH ANTIBIOTICS IN A RAT MODEL OF ACUTE CARRAGEENAN-INDUCED INFLAMMATION

Authors

  • E. O. COSOVANU Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • C. I. FOIA Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • B. I. TAMBA Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • A. SZILAGYI Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • Ivona COSTACHESCU Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • Gabriela Dumitrita STANCIU Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • Liliana Lacramioara PAVEL Dunărea de Jos University, Galati, Romania
  • Liliana MITITELU-TARTAU Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania

DOI:

https://doi.org/10.22551/

Abstract

Acute inflammation is a fundamental pathophysiological process involved in numerous diseases. The carrageenan-induced paw edema model in rodents is a well-established method for evaluating anti-inflammatory agents. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac (DCF) and ketoprofen (KET), exert their effects primarily through cyclooxygenase inhibition, while certain antibiotics, including cefuroxime (CFX) and levofloxacin (LFC), may indirectly influence inflammatory pathways. This study assessed the anti-inflammatory effects of DCF and KET, administered alone or combined with CFX or LFC, in rats with carrageenan-induced paw edema. Materials and methods: Forty-five Wistar rats were divided into nine groups (n = 5) receiving saline, NSAIDs, antibiotics, or their combinations. Treatments were given intraperitoneally every 12 hours for three days. Acute inflammation was induced by subcutaneous injection of 1% carrageenan into the right hind paw. Paw volume was measured at baseline and at 6, 24, and 72 hours. Edema was expressed as percentage increase in paw volume, and anti-inflammatory activity as percentage of edema inhibition. Statistical analysis was performed using ANOVA method. Results: Edema peaked at 6 hours after carrageenan injection. Both NSAIDs significantly reduced paw swelling at all time points, with DCF showing greater and more sustained efficacy than KET. Antibiotics alone had minimal impact, except for a modest reduction with CFX at 24 hours. Combination therapies maintained or slightly enhanced anti-inflammatory effects, particularly KET combined with CFX. Conclusions: NSAIDs were the main contributors to the anti-inflammatory response, with DCF demonstrating superior potency. Although antibiotics showed limited direct effects, certain combinations may enhance therapeutic outcomes in acute inflammation.

Author Biography

  • A. SZILAGYI, Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania

    Alexandru Ioan Cuza University of Iasi, Romania

References

1. Guay J, Bateman K, Gordon R, Mancini J, Riendeau D. Carrageenan-induced paw edema in rat elicits a predominant prostaglandin E2 (PGE2) response in the central nervous system associated with the induction of microsomal PGE2 synthase-1. J Biol Chem 2004; 279(23): 24866-24872.

2. Dhadde SS. Handbook of experimental pharmacology. India: Studium Press, 2019.

3. Qureshi O, Dua A. COX Inhibitors. [Updated 2024 Feb 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK549795/ - accessed 2.02.2026.

4. Manful CF, Fordjour E, Ikumoinein E, Abbey L, Thomas R. Therapeutic strategies targeting oxidative stress and inflammation: a narrative review. BioChem 2025; 5(4): 35.

5. Olry de Labry Lima A, Salamanca-Fernandez E, et al. Safety considerations during prescription of non-steroidal anti-inflammatory drugs (NSAIDs), through a review of systematic reviews. An Sist Sanit Navar 2021; 44: 261-273.

6. Alfaro RA, Davis DD. Diclofenac. [Updated 2023 May 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK557879/ - accessed 29.01.2026.

7. Chkhikvadze L, Chikobava E, Hariharan N, Omprakash A, Aamil SM. Awareness of the use of non-steroidal anti-inflammatory drugs: A cross-sectional study. Med Int (Lond) 2025; 5(5): 49.

8. Ghlichloo I, Gerriets V. Nonsteroidal anti-inflammatory drugs (NSAIDs) [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/sites/books/NBK547742/. Accessed 28.01.2026.

9. Omole AE, Awosika AO, Patel P. Cefuroxime. [Updated 2024 Jan 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan.

Available from: https://www.ncbi.nlm.nih.gov/books/NBK599503/. Accessed 12.02.2026.

10. Podder V, Patel P, Sadiq NM. Levofloxacin. [Updated 2024 Mar 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK545180/. Accessed 05.02.2026.

11. Vazquez E, Navarro M, Salazar Y, et al. Systemic changes following carrageenan-induced paw inflammation in rats. Inflamm Res 2015; 64(5): 333-342.

12. Patil KR, Mahajan UB, Unger BS, et al. Animal models of inflammation for screening of anti-inflammatory drugs: implications for the discovery and development of phyto-pharmaceuticals. Int J Mol Sci 2019; 20(18): 4367.

13. Morris CJ. Carrageenan-induced paw edema in the rat and mouse. Methods Mol Biol 2003; 225: 115-21.

14. https://eur-lex.europa.eu/eli/dir/2010/63/oj. Accessed 1.02.2026.

15. https://legislatie.just.ro/Public/DetaliiDocument/52457. Accessed 1.02.2026.

16. Annamalai P, Thangam EB. Local and systemic profiles of inflammatory cytokines in carrageenan-induced paw inflammation in rats. Immunol Invest 2017; 46(3): 274-283.

17. Fehrenbacher JC, McCarson KE. Models of inflammation: carrageenan air pouch. Curr Protoc 2021; 1(8): e183.

18. Dai X, Ding M, Zhang W, et al. Anti-inflammatory effects of different elution fractions of er-miao-san on acute inflammation induced by carrageenan in rat paw tissue. Med Sci Monit 2019; 25: 7958-7965.

19. Duarte DB, Vasko MR, Fehrenbacher JC. Models of inflammation: carrageenan air pouch. Curr Protoc Pharmacol 2016; 72: 5.6.1-9.

20. Ju Z, Li M, Xu J, Howell DC, Li Z, Chen FE. Recent development on COX-2 inhibitors as promising anti-inflammatory agents: The past 10 years. Acta Pharm Sin B 2022; 12(6): 2790-2807.

21. Shirakawa K, Takeno M, Kuma H, Terahara T, Yamaguchi S. Comparative evaluation of cyclooxygenase inhibition profiles across various NSAID forms and doses: implications for efficacy and adverse effects. Pain Ther 2025; 14(1): 329-338.

22. Yudhawati R, Wicaksono NF. Immunomodulatory effects of fluoroquinolones in community-acquired pneumonia-associated acute respiratory distress syndrome. Biomedicines 2024; 12(4): 761.

23. Nugrahani I, Herawati D, Wibowo MS. The benefits and challenges of antibiotics-non-steroidal anti-inflammatory drugs non-covalent reaction. Molecules 2023; 28(9): 3672.

24. Dronik M, Stasevych M. Expanding horizons: opportunities for diclofenac beyond traditional use - a review. Scientia Pharmaceutica 2025; 93(3): 31.

25. Yarahmadi A, Najafiyan H, Yousefi MH, et al. Beyond antibiotics: exploring multifaceted approaches to combat bacterial resistance in the modern era: a comprehensive review. Front Cell Infect Microbiol 2025; 15: 1493915.

Additional Files

Published

2026-04-01