The efficacy of captopril and 5-fluorouracil combination in the proliferation and collagen deposition of keloid fibroblast

https://doi.org/10.22146/ijbiotech.69505

Jesslyn Amelia(1*), Yohanes Widodo Wirohadidjojo(2), Agnes Sri Siswati(3)

(1) Department of Dermatology and Venereology, Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta 55281, Indonesia
(2) Department of Dermatology and Venereology, Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta 55281, Indonesia
(3) Department of Dermatology and Venereology, Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta 55281, Indonesia
(*) Corresponding Author

Abstract


Keloid is a benign fibroproliferative tissue growth that exceeds the initial wound margins. Captopril has been tested in vitro to reduce fibroblast proliferation and collagen deposition; thus, it has potential for use in the treatment of keloids. Meanwhile, 5‐fluorouracil (5‐FU) has already been used in keloid management. This study aimed to determine the efficacy of the combination of captopril and 5‐FU in keloid fibroblast cultures. Keloid tissues were cultured up to passages 4–7. The study consisted of a control group, captopril in various concentrations (10‐2, 10‐3, 10‐4, and 10‐5 mol/L), 5‐FU 1 mg/mL and a combination of captopril at various concentrations with 5‐FU 1 mg/mL. After 144 hours of treatment, fibroblast proliferation and collagen deposition were measured. The study showed a significant decrease in the mean index of fibroblast proliferation and collagen deposition in the group receiving captopril in various concentrations (10‐2, 10‐3, 10‐4, and 10‐5 mol/L) and the 5‐FU group against the control group (p<0.05). In the combined‐dose group, captopril at a concentration of 10‐2 mol/L and 5‐FU showed a significant reduction in fibroblast proliferation and collagen deposition compared to the 5‐FU group and the captopril at the same dose (p<0.05). In conclusion, the combination of captopril 10‐2 mol/L and 5‐FU 1 mg/mL is better at reducing fibroblast proliferation and collagen deposition in keloid fibroblast cultures than captopril or 5‐FU as a single therapeutic agent.


Keywords


5‐fluorouracil; captopril; collagen deposition; fibroblast proliferation; keloid fibroblast

Full Text:

PDF


References

Akaa PD, Ahachi NC, Vhriterhire AR, Agada E, Jenrola AA. 2017. Five year retrospective study on keloid management. J. Adv. Med. Med. Res. 23(6):1–8. doi:10.9734/JAMMR/2017/34824.

Chen J, Zhao S, Liu Y, Cen Y, Nicolas C. 2016. Ef­fect of captopril on collagen metabolisms in keloid fibroblast cells. ANZ J. Surg. 86(12):1046–1051. doi:10.1111/ans.12670.

Fang Q, Wang X, Zhao W, Chen C, Zhang M, Shi B. 2018a. The source of ACE during scar formation is from both bone marrow and skin tissue. Fed. Am. Soc. Exp. Biol. 32:1–10. doi:10.1096/fj.201701575RRR.

Fang Q, Wang X, Zhao W, Ding S, Shi B. 2018b. Angiotensin­converting enzyme inhibitor reduces scar formation by inhibiting both canonical and non­ canonical TGF­β1 pathways. Sci. Rep. 8:1–10. doi:10.1038/s41598­018­21600­w.

Gauglitz G, Korting H. 2011. Hypertrophic scar­ring and keloids : Pathomechanism and emerging treatment strategies. Mol. Med. 17(1–2):113–125. doi:10.2119/molmed.2009.00153.

Huang L, Cai YJ, Lung I, Leung BCS, Burd A. 2013. A study of the combination of triamci­nolone and 5­fluorouracil in modulating keloid fi­broblasts in vitro. Br. J. Plast. Surg. 66(9):251–259. doi:10.1016/j.bjps.2013.06.004.

Huang L, Wong YP, Cai YJ, Lung I, Leung CS, Burd A. 2010. Low­dose 5­fluorouracil induces cell cy­cle G2 arrest and apoptosis in keloid fibroblasts. Br. J. Dermatol. 163:1181–1185. doi:10.1111/j.13652133.2010.09939.x.

Mari W, Alsabri SG, Tabal N, Younes S, Sherif A, Simman R. 2016. Novel insights on understanding of keloid scar: Article review. J. Am. Coll. Clin. Wound Spec. 7(1–3):1–7. doi:10.1016/j.jccw.2016.10.001.

Mauviel A, Verrecchia F, Wendling J, Aim E. 2003. 5­Fluorouracil blocks transforming growth fac­tor beta– induced alpha2 type I collagen gene ( COL1A2 ) expression in human fibroblasts via c­Jun NH 2 ­terminal kinase / activator protein­ 1 activation. Mol. Pharmacol. 64(3):707–713. 369 doi:10.1016/j.matbio.2015.05.007.

Morihara K, Takai S, Takenaka H, Sakaguchi M, Okamoto Y, Morihara T, Miyazaki M, Kishimoto S. 2006. Cu­taneous tissue angiotensin converting enzyme may participate in pathologic scar formation in human skin. J. Am. Acad. Dermatol. 54(2):251–257. doi:10.1016/j.jaad.2005.09.027.

Salati SA. 2019. Keloids – An extensive review in the light of recent. J. Pakistan Assoc. Dermatol. 29(2):225–249.

Shah VV, Aldahan AS, Mlacker S, Alsaidan M. 2016. 5­fluorouracil in the treatment of keloids and hypertrophic scars : A comprehensive review of the litera­ture. doi:10.1007/s13555­016­0118­5.

Shaheen A. 2018. Comprehensive review of keloid formation. Clin. Res. Dermatol. 4(5):1–18. doi:10.15226/2378­1726/4/5/00168.

Vijayakumar A, Sanghvi H, Murdeshwar P. 2015. Ef­fect of enalapril on hypertrophic scars and keloids. J. Adv. Plast. Surg. Res. 1:10–13. doi:10.31907/2414­2093.2015.01.3.



DOI: https://doi.org/10.22146/ijbiotech.69505

Article Metrics

Abstract views : 1347 | views : 1122

Refbacks

  • There are currently no refbacks.


Copyright (c) 2022 The Author(s)

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.