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Ascorbic acid and calcitriol reduce TNF-α to improve the viability of modified McFarlane random skin flaps in Wistar rats

  • Rosalyn Devina Santoso ,
  • Agus Roy Rusly Hariantana Hamid ,
  • Tjokorda Gde Bagus Mahadewa ,
  • I Gusti Putu Hendra Sanjaya ,
  • Ni Nyoman Sri Budayanti ,
  • Sianny Herawati ,


Abstract

Link of Video Abstract: https://youtu.be/8UIEdUv8za8

 

Introduction: Distal flap necrosis is one of the most common complications in flap procedure. Ascorbic acid (vitamin C) is one of the most widespread antioxidants available, while calcitriol, a metabolite of vitamin D, has anti-inflammatory and antioxidant properties. The purpose of this study was to determine the effect of ascorbic acid and calcitriol on the viability of Modified McFarlane random skin flaps in Wistar rats and its mechanism through suppression of proinflammatory cytokine Tumor Necrosis Factor-α (TNF-α).

Methods: An experimental study used 28 Wistar rats, by creating a caudally based 3 cm x 9 cm Modified McFarlane random skin flap and divided into four groups. The first group was injected with 200 mg/kg/day ascorbic acid, the second group with 2μg/kg/day calcitriol, and the third group with 200 mg/kg/day ascorbic acid combined with 2μg/kg/day calcitriol was injected two hours after flap elevation for seven days, respectively. The control group was not given any intraperitoneal injection. After seven days, the percentage of flap viability rate was measured and tissue sampling was performed to measure the amount of capillary density and TNF-α in all groups.

Results: The higher percentage of viable flap area was found in all treatment groups, the highest in the ascorbic acid group 80.63% (p<0.001). The highest capillary density was found in ascorbic acid combined with the calcitriol group (27/visual field, p<0.001) compared to all groups. It was also found that the amount of TNF-α in the tissue was lowest in the group administered by ascorbic acid combined with calcitriol compared to all groups 57.38 ng/L and 0.62 nmol/mL respectively compared to all groups (p<0.001). The higher percentage of viable flap area was correlated with a lower amount of TNF-α (p<0.001), but not correlated with the amount of capillary density (p>0.05).

Conclusion: Ascorbic acid in combination with calcitriol improves the viability of Modified McFarlane random skin flaps by lowering TNF-α levels.

Keywords: Modified McFarlane random skin flap flap viability TNF- α Calcitriol Ascorbic acid

References

  1. Zhou KL, Zhang YH, Lin DS, Tao XY, Xu HZ. Effects of calcitriol on random skin flap survival in rats. Scientific reports. 2016;6(1):18945. Available at: https://doi.org/10.1038/srep18945
  2. Luo Z, Bian Y, Zheng G, Wang H, Yan B, Su W, et al. Chemically modified SDF-1α mRNA promotes random flap survival by activating the SDF-1α/CXCR4 axis in rats. Frontiers in Cell and Developmental Biology. 2021;9:623959. Available at: https://doi.org/10.3389/fcell.2021.623959
  3. Baker S. Local flaps in facial reconstruction. 4th ed. London: Elsevier. 2022.
  4. Camargo CP, Margarido NF, Guandelini E, Vieira GA, Jacomo AL, Gemperli R. Description of a new experimental model skin flap for studying skin viability in rats. Acta Cir. Bras. 2014;29:166-70.
  5. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: a cellular perspective. Physiological reviews. 2019;99(1):665-706. Available at: https://doi.org/10.1152/physrev.00067.2017
  6. Page MJ, Bester J, Pretorius E. The inflammatory effects of TNF-α and complement component 3 on coagulation. Scientific reports. 2018;8(1):1812. Available at: https://doi.org/10.1038/s41598-018-20220-8
  7. Name, J., Souza, A., Vasconcelos, A., Prado, P. and Pereira, C., 2020. Zinc, Vitamin D and Vitamin C: Perspectives for COVID-19 With a Focus on Physical Tissue Barrier Integrity. Frontiers in Nutrition, 7. Available at: https://doi.org/10.3389/fnut.2020.606398
  8. Wald E, Badke C, Hintz L, Spewak M and Sanchez-Pinto L. Vitamin therapy in sepsis. Pediatric Research. 2021;91(2):328-36. Available at: https://doi.org/10.1038/s41390-021-01673-6
  9. Nosenko MA, Ambaryan SG, Drutskaya MS. Proinflammatory cytokines and skin wound healing in mice. Molecular Biology. 2019;53:653-64. Available at: https://doi.org/10.1134/s0026893319050121
  10. Serin M, Bayramicli M. Experimental Rat Flap Models. Issues in Flap Surgery. 2018:25. Available at: https://doi.org/10.5772/intechopen.69923
  11. Kianian F, Karimian SM, Kadkhodaee M, Takzaree N, Seifi B, Sadeghipour HR. Protective effects of ascorbic acid and calcitriol combination on airway remodelling in ovalbumin-induced chronic asthma. Pharmaceutical Biology. 2020;58(1):107-15. Available at: https://doi.org/10.1080/13880209.2019.1710218
  12. Wijaya IP, Hamid AR, Mahadewa TG, Sanjaya IG, Adnyana IM, Suyasa IK. Supplementation of high-dose ascorbic acid reduces necrosis on random dorsal skin flap in rats. International Journal of Surgery Open. 2022;46:100525. Available at: https://doi.org/10.1016/j.ijso.2022.100525 .
  13. Haddad Kashani H, Seyed Hosseini E, Nikzad H, Soleimani A, Soleimani M, Tamadon MR, et al. The effects of vitamin D supplementation on signaling pathway of inflammation and oxidative stress in diabetic hemodialysis: a randomized, double-blind, placebo-controlled trial. Frontiers in pharmacology. 2018;9:50-9. Available at: https://doi.org/10.3389/fphar.2018.00050
  14. Park K. Role of micronutrients in skin health and function. Biomolecules & therapeutics. 2015;23(3):207. Available at: https://doi.org/10.4062/biomolther.2015.003
  15. Tripathi P, Nair S, Singh BP, Arora N. Mutated glutathione S-transferase in combination with reduced glutathione shows a synergistic effect in ameliorating oxidative stress and airway inflammation. Free Radical Biology and Medicine. 2010;48(6):839-44.
  16. Purwanthi IG, Hamid AR, Mahadewa TG, Adnyana IM, Sanjaya IG, Herawati S, et al. Administration of botulinum toxin a and vascular endhotelial growth factor reduce norepinephrine levels and increase viability of modified mcfarlane flap in wistar rat. International Journal of Health Sciences. 2022;6(S7):48435–51.
  17. Gęgotek A, Skrzydlewska E. Antioxidative and anti-inflammatory activity of ascorbic acid. Antioxidants. 2022;11(10):1993. Available at: https://doi.org/10.3390/antiox11101993
  18. Kianian F, Karimian SM, Kadkhodaee M, Takzaree N, Seifi B, Adeli S, et al. Combination of ascorbic acid and calcitriol attenuates chronic asthma disease by reductions in oxidative stress and inflammation. Respiratory Physiology & Neurobiology. 2019;270:103265. Available at: https://doi.org/10.1016/j.resp.2019.103265
  19. Heriansyah T, Dimiati H, Hadi TF, Umara DA, Riandi LV, Fajri F, et al. Ascorbic Acid vs Calcitriol in Influencing Monocyte Chemoattractant Protein-1, Nitric Oxide, Superoxide Dismutase, as Markers of Endothelial Dysfunction: In Vivo Study in Atherosclerosis Rat Model. Vasc Health Risk Manag. 2023;19:139-44. Available at: https://doi.org/10.2147/VHRM.S401521. PMID: 36936550; PMCID: PMC10019521.

How to Cite

Santoso, R. D., Hamid, A. R. R. H. ., Mahadewa , T. G. B. ., Sanjaya, I. G. P. H. ., Budayanti, N. N. S. ., & Herawati, S. . (2023). Ascorbic acid and calcitriol reduce TNF-α to improve the viability of modified McFarlane random skin flaps in Wistar rats. Bali Medical Journal, 12(3), 2981–2985. https://doi.org/10.15562/bmj.v12i3.4843
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Rosalyn Devina Santoso
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Agus Roy Rusly Hariantana Hamid
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Tjokorda Gde Bagus Mahadewa
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I Gusti Putu Hendra Sanjaya
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Ni Nyoman Sri Budayanti
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Sianny Herawati
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BMJ Journal