The Effect of Topical and Oral Phenytoin on Increasing Wound Healing of Enterocutaneus Fistula in Wistar Rat


  • Victor Kurniawan Biomedical Master Program, Diponegoro University, Semarang, Indonesia
  • Hardian Hardian Department of Physiology, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
  • Ignatius Riwanto Department of Digestive Surgery, Faculty of Medicine, Diponegoro University, Semarang, Indonesia



Enterocutaneous fistula, Phenytoin, Wound healing


BACKGROUND: Enterocutaneous fistula is an abnormal connection between gastrointestinal tract with skin or wound and studies showed low numbers of spontaneous fistula closure (20–30%) despite proper wound treatment and nutrition with high morbidity and mortality rate in fistula repair operation. Phenytoin, commonly used as an anticonvulsant, has shown its effects on wound healing process such as promoting fibroblast activities, formation of granulation tissue, reduction of collagenase activities, increasing collagen production, and other connective tissue components, reducing bacterial colonization, and reducing wound exudate.

AIM: To assess the effects of phenytoin in enterocutaneous fistula wound healing in Wistar rats (Ratus norvegicus).

MATERIALS AND METHODS: This is an experimental study with randomized post-test only design on 20 Winstar rats. A 5 mm enterocutaneous fistula was made on the rat’s stomach and the rats were assigned randomly into three groups: K (control), P1 (10% phenytoin ointment), and P2 (0.03 mg/g oral phenytoin). The groups were terminated on day 7 and wound histological slides were made. The data were analyzed using SPSS software.

RESULTS: The delta diameter is highest in P1 group (mean + SD 0.928 + 0.078), followed by P2 (mean + SD 0.770 + 0.145), and control (mean + SD 0.411 + 0.120). There is a significant difference, p < 0.05 (0.000), between P1 and P2, indicating that oral phenytoin is more effective in collagen formation than topical phenytoin. There is no significant difference between P1 and P2, p < 0.05 (0.269), indicating that oral phenytoin is not more effective than topical phenytoin in granulation tissue in enterocutaneous fistula in Wistar rats.

CONCLUSION: Administration of topical and oral phenytoin was effective in increasing granulation tissue thickness, increasing collagen amount in wound tissue, and reducing the diameter of enterocutaneous fistulas in Wistar rats compared with control on the seventh day.


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How to Cite

Kurniawan V, Hardian H, Riwanto I. The Effect of Topical and Oral Phenytoin on Increasing Wound Healing of Enterocutaneus Fistula in Wistar Rat. Open Access Maced J Med Sci [Internet]. 2022 Jan. 25 [cited 2023 Mar. 31];10(A):997-1000. Available from: