J Appl Biomed 22:67-73, 2024 | DOI: 10.32725/jab.2024.010

Does vanillic acid affect fracture healing? An experimental study in a rat model of femur fracture

Ahmet Yurteri1, Numan Mercan2, *, Mehmet Kiliç1, Murat Çelik3, Fatih Doğar4, Ahmet Yildirim1
1 Konya City Hospital, Department of Orthopaedics and Traumatology, Konya, Turkey
2 Kahramanmaras Necip Fazil City Hospital, Department of Orthopaedics and Traumatology, Kahramanmaras, Turkey
3 Selcuk University Faculty of Medicine, Department of Medical Pathology, Konya, Turkey
4 Kahramanmaras Sutcu Imam University, Faculty of Medicine, Department of Orthopaedics and Traumatology, Kahramanmaras, Turkey

Background and objectives: We aimed to determine the effects of vanillic acid (VA) on fracture healing radiologically, histologically, immunohistochemically, and biomechanically using a rat femur open fracture injury model.

Methods: 32 male Wistar-Albino rats were used and divided into two groups: the study group (VA) and the control group. From the time they were operated on until they were sacrificed, the rats in the study group were given 100 mg/kg/day VA by oral gavage. After sacrification, the femurs were analyzed.

Results: It was observed that the Huo histological scoring was significantly higher in the VA group (p = 0.001), and the ratio of the amount of callus tissue compared to intact bone tissue was significantly higher. While no significant difference was observed in immunohistochemical H-scores in ColI antibody staining (p = 1.000), a borderline significant difference in favor of VA was observed in ColIII antibody staining (p = 0.078). In biomechanical analysis, failure load (N), total energy (J), maximum stress (MPa), and stiffness (N/mm) measurements were significantly higher in the VA group (p = 0.040, p = 0.021, p = 0.015, and p = 0.035, respectively).

Conclusion: It has been observed that VA, with its antioxidative properties, increases fracture healing in rats, in which an open fracture model was created. We are hopeful that such an antioxidant, which is common in nature, will increase fracture healing. Since this study is the first to examine the effect of VA on fracture healing, further studies are needed.

Keywords: Angelica sinensis; Fracture union; Open fracture; Phenolic compounds; Vanillic acid
Conflicts of interest:

The authors have no conflict of interest to declare.

Received: November 18, 2023; Revised: June 3, 2024; Accepted: June 12, 2024; Prepublished online: June 17, 2024; Published: June 24, 2024  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Yurteri A, Mercan N, Kiliç M, Çelik M, Doğar F, Yildirim A. Does vanillic acid affect fracture healing? An experimental study in a rat model of femur fracture. J Appl Biomed. 2024;22(2):67-73. doi: 10.32725/jab.2024.010. PubMed PMID: 38912861.
Download citation

References

  1. Amanvermez R, Gunay M, Piskin A, Keles G, Tomak L (2013). TNF-α, IL-1β, and oxidative stress during fracture healing with or without ankaferd. Bratisl Lek Listy 114(11): 621-624. DOI: 10.4149/bll_2013_132. Go to original source... Go to PubMed...
  2. Apaja-Sarkkinen M, Autio-Harmainen H, Alavaikko M, Risteli J, Risteli L (1986). Immunohistochemical study of basement membrane proteins and type III procollagen in myelofibrosis. Br J Haematol 63(3): 571-580. DOI: 10.1111/j.1365-2141.1986.tb07535.x. Go to original source... Go to PubMed...
  3. Bentley SA, Alabaster O, Foidart JM (1981). Collagen heterogeneity in normal human bone marrow. Br J Haematol 48(2): 287-291. Go to original source...
  4. Calixto-Campos C, Carvalho TT, Hohmann MS, Pinho-Ribeiro FA, Fattori V, Manchope MF, et al. (2015). Vanillic Acid Inhibits Inflammatory Pain by Inhibiting Neutrophil Recruitment, Oxidative Stress, Cytokine Production, and NFκB Activation in Mice. J Nat Prod 78(8): 1799-1808. DOI: 10.1021/acs.jnatprod.5b00246. Go to original source... Go to PubMed...
  5. Charrouf Z, Guillaume D (2007). Phenols and polyphenols from Argania spinosa. Am J Food Technol 2(7): 679-683. DOI: 10.3923/ajft.2007.679.683. Go to original source...
  6. Circosta C, Pasquale RD, Palumbo DR, Samperi S, Occhiuto F (2006). Estrogenic activity of standardized extract of Angelica sinensis. Phytother Res 20(8): 665-669. DOI: 10.1002/ptr.1928. Go to original source... Go to PubMed...
  7. Claes L, Recknagel S, Ignatius A (2012). Fracture healing under healthy and inflammatory conditions. Nat Rev Rheumatol 8(3): 133-143. DOI: 10.1038/nrrheum.2012.1. Go to original source... Go to PubMed...
  8. Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H, et al. (2013). Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone and Miner Res 28(1): 2-17. DOI: 10.1002/jbmr.1805. Go to original source... Go to PubMed...
  9. DePhillipo NN, Aman ZS, Kennedy MI, Begley JP, Moatshe G, LaPrade RF (2018). Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review. Orthop J Sports Med 6(10): 2325967118804544. DOI: 10.1177/2325967118804544. Go to original source... Go to PubMed...
  10. Einhorn TA, Gerstenfeld LC (2015). Fracture healing: mechanisms and interventions. Nat Rev Rheumatol 11(1): 45-54. DOI: 10.1038/nrrheum.2014.164. Go to original source... Go to PubMed...
  11. Gálvez MC, Barroso CG, Pérez-Bustamante JA (1994). Analysis of polyphenolic compounds of different vinegar samples. Z Lebensm Unters Forch 199(1): 29-31. DOI: 10.1007/BF01192948. Go to original source...
  12. Huo MH, Troiano NW, Pelker RR, Gundberg CM, Friedlaender GE (1991). The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res 9(3): 383-390. DOI: 10.1002/jor.1100090310. Go to original source... Go to PubMed...
  13. Maruyama M, Rhee C, Utsunomiya T, Zhang N, Ueno M, Yao Z, Goodman SB (2020). Modulation of the Inflammatory Responseand Bone Healing. Front Endocrinol 11: 386. DOI: 10.3389/fendo.2020.00386. Go to original source... Go to PubMed...
  14. Miller EJ (1973). A review of biochemical studies on the genetically distinct collagens of the skeletal system. Clin Orthop Relat Res (92): 260-280. DOI: 10.1097/00003086-197305000-00024. Go to original source... Go to PubMed...
  15. Müller PK, Raisch K, Matzen K, Gay S (1977). Presence of type III collagen in bone from a patient with osteogenesis imperfecta. Eur J Pediatr 125(1): 29-37. DOI: 10.1007/BF00470603. Go to original source... Go to PubMed...
  16. Pacheco-Palencia LA, Mertens-Talcott S, Talcott ST (2008). Chemical composition, antioxidant properties, and thermal stability of a phytochemical enriched oil from Acai (Euterpe oleracea Mart.). J Agric Food Chem 56(12): 4631-4636. DOI: 10.1021/jf800161u. Go to original source... Go to PubMed...
  17. Recker RR, Kimmel DB, Dempster D, Weinstein RS, Wronski TJ, Burr DB (2011). Issues in modern bone histomorphometry. Bone 49(5): 955-964. DOI: 10.1016/j.bone.2011.07.017. Go to original source... Go to PubMed...
  18. Sheweita SA, Khoshhal KI (2007). Calcium metabolism and oxidative stress in bone fractures: role of antioxidants. Curr Drug Metab 8(5): 519-525. DOI: 10.2174/138920007780866852. Go to original source... Go to PubMed...
  19. Szczêsny G (2015). Fracture Healing and its Disturbances. A Literature Review. Ortop Traumatol Rehabil 17(5): 437-454. DOI: 10.5604/15093492.1186809. Go to original source... Go to PubMed...
  20. Topak D, Gürbüz K, Doğar F, Bakir E, Gürbüz P, Kilinç E, et al. (2023). Hydroxychloroquine induces oxidative stress and impairs fracture healing in rats. Jt Dis Relat Surg 34(2): 346-355. DOI: 10.52312/jdrs.2023.976. Go to original source... Go to PubMed...
  21. Volk SW, Shah SR, Cohen AJ, Wang Y, Brisson BK, Vogel LK, et al. (2014). Type III collagen regulates osteoblastogenesis and the quantity of trabecular bone. Calcif Tissue Int 94(6): 621-631. DOI: 10.1007/s00223-014-9843-x. Go to original source... Go to PubMed...
  22. Wang YG, Jiang LB, Gou B (2017). Protective effect of vanillic acid on ovariectomy-induced osteoporosis in rats. Afr J Tradit Complement Altern Med 14(4): 31-38. DOI: 10.21010/ajtcam.v14i4.4. Go to original source... Go to PubMed...
  23. Xiao HH, Gao QG, Zhang Y, Wong KC, Dai Y, Yao XS, Wong MS (2014). Vanillic acid exerts oestrogen-like activities in osteoblast-like UMR 106 cells through MAP kinase (MEK/ERK)-mediated ER signaling pathway. J Steroid Biochem Mol Biol 144 Pt B: 382-391. DOI: 10.1016/j.jsbmb.2014.08.002. Go to original source... Go to PubMed...
  24. Zhang Y, Li Q, Wan HY, Xiao HH, Lai WP, Yao XS, Wong MS (2011). Study of the mechanisms by which Sambucus williamsii HANCE extract exert protective effects against ovariectomy-induced osteoporosis in vivo. Osteoporosis Int 22(2): 703-709. DOI: 10.1007/s00198-010-1240-3. Go to original source... Go to PubMed...

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0), which permits non-comercial use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.