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The effect of oral phenytoin and vitamin C therapy on enterocutaneous fistula healing

  • Yohannes Sugiarto ,
  • Ignatius Riwanto ,
  • Trilaksana Nugroho ,


Abstract

Introduction: Phenytoin is reported to heal the enterocutaneous fistula. Meanwhile, vitamin C is known to improve wound healing. The comparison of phenytoin and vitamin C in the treatment of enterocutaneous fistula is never reported.

Methods: A randomized controlled trial with a post-test-only group design using artificial enterocutaneous fistula Ratus Norvegicus male Wistar rats were reported. Rats were divided into four groups randomly, namely, Control (K), Treatment 1: combined phenytoin and vitamin C (P1), Treatment 2: phenytoin (P2), and Treatment 3: vitamin C (P3). Variables under study were a number of fibroblast and angiogenesis. One Way Anova test, followed by the Post-Hoc Test, was used to test the difference among and between groups.

Results: The mean value of fibroblasts in groups K (501.86 ± 107.10), P1 (861.53 ± 25.99), P2 (719.93 ± 24.61), P3 (781.46 ± 28.23). The mean value of angiogenesis in groups K (18.63 ± 4.24), P1 (48.86 ± 10.23), P2 (26.26 ± 1.64), P3 (31.96 ± 2.97). The Post-Hoc test showed that were significant differences in the number of fibroblasts and angiogenesis from the group given a combination of oral phenytoin and vitamin C therapy compared to the group given oral phenytoin, vitamin C, and control (p <0.05).

Conclusion: A combination of oral phenytoin and vitamin C therapy increased the number of fibroblasts and angiogenesis of enterocutaneous fistula in Wistar rats, better than single.

Keywords: angiogenesis enterocutaneous fistula fibroblasts phenytoin vitamin C

References

  1. Lee SH. Surgical management of enterocutaneous fistula. Korean J Radiol. 2012;13 Suppl 1(Suppl 1):S17-S20. doi:10.3348/kjr.2012.13.S1.S17.
  2. Dodiyi MA and Wichendu PN. Current concepts in the management of enterocutaneous fistula. International Surgery Journal. 2018;5(6). p1981-1985. doi:http://dx.doi.org/10.18203/2349-2902.isj20181836
  3. Galbreath T, Perea L. Enterocutaneous Fistula. Acute Care General Surgery: Springer; 2017. p. 35-43.
  4. Cowan KB, Cassaro S. Enterocutaneous Fistula. [Updated 2022 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459129/.
  5. Dubose JJ, Lundy JB. Enterocutaneous fistulas in the setting of trauma and critical illness. Clin Colon Rectal Surg. 2010;23(3):182-189. doi:10.1055/s-0030-1262986.
  6. Gribovskaja-Rupp I, Melton GB. Enterocutaneous Fistula: Proven Strategies and Updates. Clin Colon Rectal Surg. 2016;29(2):130-137. doi:10.1055/s-0036-1580732.
  7. Tuma F, Crespi Z, Wolff CJ, Daniel DT, Nassar AK. Enterocutaneous Fistula: A Simplified Clinical Approach. Cureus. 2020;12(4):e7789. Published 2020 Apr 22. doi:10.7759/cureus.7789.
  8. Wainstein DE, Fernandez E, Gonzalez D, Chara O, Berkowski D. Treatment of high-output enterocutaneous fistulas with a vacuum-compaction device. A ten-year experience [published correction appears in World J Surg. 2008 Mar;32(3):429]. World J Surg. 2008;32(3):430-435. doi:10.1007/s00268-007-9235-8.
  9. Lambert KV, Hayes P, McCarthy M. Vacuum assisted closure: a review of development and current applications. Eur J Vasc Endovasc Surg. 2005;29(3):219-226. doi:10.1016/j.ejvs.2004.12.017.
  10. Wang W, Pan Z, Hu X, Li Z, Zhao Y, Yu AX. Vacuum-assisted closure increases ICAM-1, MIF, VEGF and collagen I expression in wound therapy. Exp Ther Med. 2014;7(5):1221-1226. doi:10.3892/etm.2014.1567.
  11. Limengka Y, Jeo WS. Spontaneous closure of multiple enterocutaneous fistula due to abdominal tuberculosis using negative pressure wound therapy: a case report. J Surg Case Rep. 2018;2018(1):rjy001. Published 2018 Jan 25. doi:10.1093/jscr/rjy001.
  12. Keppel Hesselink JM. Phenytoin repositioned in wound healing: clinical experience spanning 60 years. Drug Discov Today. 2018;23(2):402-408. doi:10.1016/j.drudis.2017.09.020.
  13. Jaber S, Rihy Z, Joseph R, Al-Khayat M. Does phenytoin improve the healing of gastrointestinal fistulas?. Case Rep Gastroenterol. 2011;5(1):52-55. Published 2011 Jan 14. doi:10.1159/000322938.
  14. Hasamnis A, Mohanty B, Muralikrishna, Patil S. Evaluation of wound healing effect of topical phenytoin on excisional wound in albino rats. J Young Pharm. 2010;2(1):59-62. doi:10.4103/0975-1483.62215.
  15. Bhatia A, Prakash S. Topical phenytoin for wound healing. Dermatol Online J. 2004;10(1):5.
  16. Serra R, Al-Saidi AG, Angelov N, Nares S. Suppression of LPS-induced matrix-metalloproteinase responses in macrophages exposed to phenytoin and its metabolite, 5-(p-hydroxyphenyl-), 5-phenylhydantoin. J Inflamm (Lond). 2010;7:48. Published 2010 Sep 15. doi:10.1186/1476-9255-7-48.
  17. Moores J. Vitamin C: a wound healing perspective. British journal of community nursing. 2013;18(Sup12):S6-S11. https://doi.org/10.12968/bjcn.2013.18.Sup12.S6.
  18. Mohammed BM, Fisher BJ, Kraskauskas D, et al. Vitamin C promotes wound healing through novel pleiotropic mechanisms. Int Wound J. 2016;13(4):572-584. doi:10.1111/iwj.12484.
  19. Sawicka-Glazer E, Czuczwar SJ. Vitamin C: a new auxiliary treatment of epilepsy?. Pharmacol Rep. 2014;66(4):529-533. doi:10.1016/j.pharep.2014.02.016.
  20. Saraswathy G, Maheswari E, Santhrani T. Effect of vitamin C supplementation on phenytoin induced hepatotoxicity. Global J Pharmacol. 2010;4(3):127-35.
  21. Wallace HA, Basehore BM, Zito PM. Wound Healing Phases. In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2022.
  22. Song KH. New techniques for treating an anal fistula. J Korean Soc Coloproctol. 2012;28(1):7-12. doi:10.3393/jksc.2012.28.1.7.
  23. Lu F, Ogawa R, Nguyen DT, et al. Microdeformation of three-dimensional cultured fibroblasts induces gene expression and morphological changes. Ann Plast Surg. 2011;66(3):296-300. doi:10.1097/SAP.0b013e3181ea1e9b.
  24. Jaber SA, Fallatah BM, Tayara B, Yami H, Abdelmoeti M. Intravenous Phenytoin: Potential New Therapy for Gastrointestinal Fistlae. Global Journal of Surgery. 2013;1(3):11-4. DOI:10.12691/js-1-3-1.
  25. Honnegowda TM, Kumar P, Udupa EGP, Kumar S, Kumar U, Rao P. Role of angiogenesis and angiogenic factors in acute and chronic wound healing. Plast Aesthet Res 2015;2:243-9. http://dx.doi.org/10.4103/2347-9264.165438.
  26. Corrêa JD, Queiroz-Junior CM, Costa JE, Teixeira AL, Silva TA. Phenytoin-induced gingival overgrowth: a review of the molecular, immune, and inflammatory features. ISRN Dent. 2011;2011:497850. doi:10.5402/2011/497850.
  27. Zhou D, Huang C, Lin Z, et al. Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. Cell Signal. 2014;26(2):192-197. doi:10.1016/j.cellsig.2013.11.004.
  28. Rőszer T. Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms. Mediators Inflamm. 2015. doi:10.1155/2015/816460.

How to Cite

Yohannes Sugiarto, Ignatius Riwanto, & Trilaksana Nugroho. (2022). The effect of oral phenytoin and vitamin C therapy on enterocutaneous fistula healing. Bali Medical Journal, 11(3), 1441–1447. https://doi.org/10.15562/bmj.v11i3.3469
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Yohannes Sugiarto
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Ignatius Riwanto
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Trilaksana Nugroho
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