Effects of Topical Pentoxifylline on Induced Thermal Burn in Mice

Authors

  • Hawraa J. Mansur Department of Pharmacology, College of Medicine, University of Al-Nahrain, Baghdad, Iraq
  • Fouad K. Gatea Department of Pharmacology, College of Medicine, University of Al-Nahrain, Baghdad, Iraq

Abstract

Objective: To evaluate the effects of topical application of pentoxifylline in the treatment of induced burn in mice and to compare it with silver sulfadiazine. Methods: Pentoxifylline-hydroxypropyl methylcellulose (HPMC) topical gel formulations were prepared by mixing homogeneously 1g of pentoxifylline with 3g of HPMC gel under continuous stirring, and the final weight was made up to 100 mL. The experimental animals (72 mice) were divided into four groups, each subdivided to three groups according to the three-day interval (7, 14, and 21st day) after thermal injury, each with eight animals. The animals were anesthetized then thermal injury was done by a metal bar. The wound surface area was measured every seven days, and the animals have been sacrificed by ether overdose at these intervals. Then, skin sections are stained with (hematoxylin and eosin) and Masson trichrome for histological scoring after being evaluated by immunohistochemical assay to estimate the expression of fibroblast growth factor and epidermal growth factor. Results: Pentoxifylline group (Gr4) showed a significant reduction in the burning area (p<0.05), PTX and SSD groups have a significant increase in immunohistochemical expression of fibroblast growth factor (FGF), epidermal growth factor (EGF) in comparison with gel base and burn without treatment (BWT) groups, and skin histopathological examination were measured on days 7, 14, and 21 of burn injury experiment. Histopathologic evaluations on day 7 showed that neovascularization induced granulation tissue was greater in the pentoxifylline group (PTX) than silver sulfadiazine (SSD), gel base, and BWT groups. On day 21, re-epithelialization scores were showed higher and maximum level in the PTX group than the SSD, gel base and BWT groups. Inflammatory cells scores in BWT, SSD, and gel base groups showed higher than PTX group. Conclusion: the results suggest that topical use of pentoxifylline showed significant efficacy in wound healing activities than silver sulfadiazine cream. Histopathological evaluation results showed significant improvement in inflammatory response, granulation tissue formation, and re-epithelization, which may be due to the anti-inflammatory, anti-oxidant, and angiogenic activity of pentoxifylline and the appropriate regulation FGF and EGF.

Keywords:

Fibroblast growth factor, Pentoxifylline, Silver sulfadiazine, Wound healing

References

1. Herndon D, ed. Chapter 4: Prevention of Burn Injuries. Total burn care (4th ed.). Edinburgh: Saunders. 2012. 46.

2. Hettiaratchy S, Dziewulski P. ABC of burns: pathophysiology and types of burns. BMJ. 2004;328(7453):1427-1429.

3. Kao CC, Garner WL. Acute burns. Plast Reconstr Surg. 2000; 105:2482-2493.

4. Garcia-Espinoza JA, Aguilar-Aragon VB, Ortiz-Villalobos EH, Garcia-Manzano RA and Antonio BA, Burns: Definition, Classification, Pathophysiology and Initial Approach. Gen Med (Los Angeles). 2017;5:298.

5. Evers L, Bhavsar D, Mailänder P. The biology of burn injury. Experimental Dermatology. 2010;19:777-783.

6. Tredget EE, Yu YM. The metabolic effects of thermal injury. World Journal of Surgery. 1992 Jan-Feb;16(1):68-79.

7. Grazul-Bilska A, Johnson M, Bilski J, Redmer D, Reynolds L,Gutiérrez-Fernández A, Inada M, Balbín M, et al. Increased inflammation delays wound healing in mice deficient in collagenase-2(MMP-8). FASEB J. 2007;21(10):2580-2591.

8. Jiang L, Dai Y, Cui F, Pan Y, Zhang H, Xiao J, Xiaobing FU. Expression of cytokines, growth factors and apoptosis-related signal molecules in chronic pressure ulcer wounds healing. Spinal Cord. 2014;52(2):145-151.

9. Katzung B, Trevor A. Basic and pharmacology. Effect of pentoxifylline on blood viscosity, Thirteen edition, 2011;342.

10. Rajan V, Murry RZ. The duplication nature of inflammation in wound repair. Wound Practice Repair J. 2008;16 (3):122-129.

11. Lu D, Song H, Li Y, Clarke J, Shi G. Pentoxifylline for endometriosis. Cochrane Database Syst Rev. 2012(1), 767.

12. Deree J, Martins JO, Melbostad H, et al. Insights into the regulation of TNF-a production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition. Clinics. 2008;63(3):321-328.

13. Wu F, Bian D, Xia Y, Gong Z, Tan Q, Chen J, Dai Y. Identification of Major Active Ingredients Responsible for Burn Wound Healing of Centella asiatica Herbs. Evid Based Complement Alternat Med. 2012; 2012:848093.

14. Siang R, Teo SY, Lee SY, Basavaraj AK, Koh RY, Rathbone MJ. Formulation and evaluation of topical pentoxifylline-hydroxypropyl methyl cellulose gels for wound healing application.International Journal of Pharmacy and Pharmaceutical Sciences. 2014;6(9). ISSN- 0975-1491.

15. Khorasani Gh, Hosseinimehr S, Zamani P, Ghasemi M, Ahmadi A. The Effect of Saffron (Crocus Sativus) Extract for Healing of Second-degree Burn Wounds in Rats. The Keio journal of medicine. 2009;57:190-5. 10.2302/kjm.57.190.

16. Hernández-Rodríguez J, Segarra M, Vilardell C et al. Tissue production of pro-inflammatory cytokines (IL-1beta, TNF alpha and IL-6) correlates with the intensity of the systemic inflammatory response and with corticosteroid requirements in giant-cell arteritis. Rheumatology (Oxford). 2004;43(3):294-301.

17. Oliveira PC, Pinheiro AL, de Castro IC et al: Evaluation of the effects of polarized light (1400-200 nm) on the healing of third-degree burns in induced diabetic and non-diabetic rats. Photomed Laser. 2011;29:619-625.

18. Moulin V, Auger FA, Garel D and Germain L. Role of wound healing myofibroblasts on re-epithelization of human skin. Burns. 2000; 26: 3.

19. Muller MJ, Hollyoak MA, Moaveni Z, Brown TL, Herndon DN, Heggers JP. Retardation of wound healing by silver sulfadiazine is reversed by Aloe vera and nystatin. Burns. 2003;(8): 834-836.

20. Hosseinimehr S, Khorasani GH, Azadbakht M, Zamani P, Ghasemi M and Ahmadi A. Effect of Aloe Cream versus Silver Sulfadiazine for Healing Burn Wounds in Rats. Acta Dermatovenerol Croa. 2010;18(1):2-7.

21. Rosen J, Landriscina A, Kutner A, et al. Silver sulfadiazine retards wound healing in mice via alterations in cytokine expression.J Invest Dermatol. 2015;135:1459-1462.

22. Simonetti O, Lucarini G, Orlando F, Pierpaoli E, Ghiselli R, Provinciali M, Castelli P, Guerrieri M, Di Primio R, Offidani A,Giacometti A, Cirioni O. Role of daptomycin on burn wound healing in an animal methicillin-resistant Staphylococcus aureus infection model. Antimicrob Agents Chemother. 2017; 61:06-17.

23. Qing C. The molecular biology in wound healing & non-healing wound. Chin J Traumatol. 2017;20(4):189-193.

24. Bhat VB, Madyastha KM. Anti-oxidant and radical scavenging properties of 8- oxo derivatives of xanthine drugs pentoxifylline and lisofylline. Biochem Biophys Res Commun. 2001;288(5): 1212-1217.

25. Sayar H, Gergerlioglu N, Seringec N, Ozturk P, Bulbuloglu E, Karabay G. Comparison of efficacy of topical phenytoin with hypericin in second-degree burn wound healing: an experimental study in rats. Medical science monitor basic research. 2014; 20: 36-46.

26. Zhang J, Hu W, Diao Q, Wang Z, Miao J, Chen X, Xue Z (). Therapeutic effect of the epidermal growth factor on diabetic foot ulcer and the underlying mechanisms. Experimental and Therapeutic Medicine. 2019;17(3),1643-1648.

Published

2021-09-06
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Vol. 12 No. 3 (2021): Volume 12,Issue3

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Articles