The Effect of Apocynin on Fat Graft Survival



In this study, we investigated the effect of apocynin on fat graft survival in a rat model.


Twenty-one Wistar albino male rats were included in the study. The grafts taken from the inguinal area were applied to the nape of each rat. The rats were randomly divided into three groups. Apocynin+DMSO, DMSO and saline were administered intraperitoneally once daily for 14 days. After 90 days, the animals were sacrificed and the grafts were excised. The weights and volumes were measured and sent for histopathological evaluation. The weight, volume, survival rates of the grafts, the number of viable cells with the MTT test and pathological parameters, inflammation, vascularization, fibrosis, lipogranuloma and cyst formation, were evaluated.


Statistically significant differences were found between the groups in survival rates (p<0.05). In paired comparisons between the groups, the parameters of viable cells and survival rates were statistically significantly higher in apocynin group compared to the other groups (p<0.05). The survival rates relating to the weight and viable cell count in the DMSO group were statistically significantly higher than in the control group (p<0.05). However, no statistically significant difference was found between the DMSO group and the control group in the survival rate in terms of volume (p<0.05). There was no significant difference between the groups in the comparison of pathological parameters (p>0.05).


Apocynin increases fat graft survival in the animal fat grafting model. Therefore, apocynin can be used as an effective medical agent to prevent the volume loss of fat grafts.

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  1. 1.

    Ozgul M, Karabagli Y, Kocman AE, Kose AA, Cetin C, Donmez DB (2018) The determination of the effect of curcumin on autologous fat graft survival in rats: experimental study. Turk J Plast Surg 26(4):144

    Google Scholar 

  2. 2.

    Sezgin B, Ozmen S (2018) Fat grafting to the face with adjunctive microneedling: a simple technique with high patient satisfaction. Turk J Med Sci 48(3):592–601

    CAS  PubMed  Google Scholar 

  3. 3.

    Guisantes E, Fontdevila J, Rodriguez G (2012) Autologous fat grafting for correction unaesthetic scars. Ann Plast Surg 69:550–554

    CAS  Article  Google Scholar 

  4. 4.

    Minn KW, Min KH, Chang H, Kim S, Heo EJ (2010) Effects of fat preparation methods on the viabilities of autologous fat grafts. Aesthet Plast Surg 34(5):626–631

    Article  Google Scholar 

  5. 5.

    MacRae JW, Tholpady SS, Ogle RC, Morgan RF (2004) Ex vivo fat graft preservation: effects and implications of cryopreservation. Ann Plast Surg 52(3):281–282

    Article  Google Scholar 

  6. 6.

    Park B, Kong JS, Kang S, Kim YW (2011) The effect of epidermal growth factor on autogenous fat graft. Aesthet Plast Surg 35(5):738–744

    Article  Google Scholar 

  7. 7.

    Por YC, Yeow VK, Louri N, Lim TK, Kee I, Song IC (2009) Platelet-rich plasma has no effect on increasing free fat graft survival in the nude Mouse. J Plast Reconstr Aesthet Surg 62(8):1030–1034

    Article  Google Scholar 

  8. 8.

    Fraga MF, Helene A Jr, Nakamura F, Lellis RF, Kikuchi W, Esteban D (2008) Comparative study of the integration and viability of autonomised and nonautonomised autologous fat tissue grafts e experimental model in rabbits. J Plast Reconstr Aesthet Surg 61(9):1044–1048

    Article  Google Scholar 

  9. 9.

    Pu LL, Coleman SR, Cui X, Ferguson RE Jr, Vasconez HC (2010) Cryopreservation of autologous fat grafts harvested with the coleman technique. Ann Plast Surg 64(3):333–337

    CAS  Article  Google Scholar 

  10. 10.

    Grewal N, Yacomotti L, Melkonyan V, Massey M, Bradley JP, Zuk PA (2009) Freezing adipose tissue grafts may damage their ability to integrate into the host. Connect Tissue Res 50(1):14–28

    CAS  Article  Google Scholar 

  11. 11.

    Kojima H, Tanaka Y, Tanaka T, Miyazaki H, Shiwa M, Kamide Y, Moriyama H (1998) Cell proliferation and apoptosis in human middle ear cholesteatoma. Arch Otolaryngol Head Neck Surg 124(3):261–264

    CAS  Article  Google Scholar 

  12. 12.

    Nishimura T, Hashimoto H, Nakanishi I, Furukawa H (2000) Microvasculer angiogenesis and apoptosis in the survival of free fat grafts. Laryngoscope 110(8):1333–1338

    CAS  Article  Google Scholar 

  13. 13.

    Katsuyama M, Matsuno K, Yabe-Nishimura C (2012) Physiological roles of NOX/NADPH oxidase, the superoxide-generating enzyme. J. Clin. Biochem. Nutr 50:9–22

    CAS  Article  Google Scholar 

  14. 14.

    Carrillo JD, Tena MT (2006) Determination of volatile oak compounds in aged wines by multiple headspace solid-phase microextraction and gas chromatography–mass spectrometry (MHS-SPME–GC–MS). Anal Bioanal Chem 385:937–943

    CAS  Article  Google Scholar 

  15. 15.

    Heumüller S, Wind S, Barbosa-Sicard E, Schmidt HH, Busse R, Schröder K, Brandes RP (2008) Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. Hypertension 51:211–217

    Article  Google Scholar 

  16. 16.

    Riganti C, Costamagna C, Bosia A, Ghigo D (2006) The NADPH oxidase inhibitor apocynin(acetovanillone) induces oxidative stress. Toxicol. Appl. Pharmacol 212:179–187

    CAS  Article  Google Scholar 

  17. 17.

    Vejrazka M, Mícek R, Stípek S (2005) Apocynin inhibits NADPH oxidase in phagocytes but stimulates ROS production in non-phagocytic cells. Biochim. Biophys. Acta 1722:143–214

    CAS  Article  Google Scholar 

  18. 18.

    Du ZD, Yu S, Qi Y, Qu TF, He L, Wei W, Liu K, Gong SS (2019) NADPH oxidase inhibitor apocynin decreases mitochondrial dysfunction and apoptosis in the ventral cochlear nucleus of D-galactose-induced aging model in rats. Neurochem Int 124:31–40

    CAS  Article  Google Scholar 

  19. 19.

    Alley MC, Scudiere DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, Abbott BJ, Mayo JG, Shoemaker RH, Boyd MR (1988) Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Can Res 48:589–601

    CAS  Google Scholar 

  20. 20.

    Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB (1987) Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Can Res 47:936–942

    CAS  Google Scholar 

  21. 21.

    International Society of Aesthetic Plastic Surgery (2019) Accessed November 15, 2019

  22. 22.

    Yuksel E, Weinfeld AB, Cleek R, Wamsley S, Jensen J, Boutros S, Waugh JM, Shenaq SM, Spira M (2000) Increased free fat-graft survival with the long-term, local delivery of insulin, insulin-like growth factor-I, and basic fibroblast growth factor by PLGA/PEG microspheres. Plast Reconstr Surg 105(5):1712–1720

    CAS  Article  Google Scholar 

  23. 23.

    Ayhan M, Senen D, Adanalı G, Gorgu M, Erdogan B, Albayrak B (2001) Use of beta blockers for increasing: survival of free fat grafts. Aesthet Plast Surg 25(5):338–342

    CAS  Article  Google Scholar 

  24. 24.

    Temiz G, Sirinoglu H, Yesiloglu N, Filinte D, Kacmaz C (2016) Effects of deferoxamine on fat graft survival. Facial Plast Surg 32(4):438–443

    CAS  Article  Google Scholar 

  25. 25.

    Luo S, Hao L, Li X, Yu D, Diao Z, Ren L, Xu H (2013) Adipose tissue-derived stem cells treated with estradiol enhance survival of autologous fat transplants. Tohoku J Exp Med 231(2):101–110

    CAS  Article  Google Scholar 

  26. 26.

    Peer LA (1955) Cell survival theory versus replacement theory. Plast Reconstr Surg 16(3):161–8

    CAS  Article  Google Scholar 

  27. 27.

    Medina MA 3rd, Nguyen JT, Kirkham JC (2011) Polymer therapy: a novel treatment to improve fat graft viability. Plast Reconstr Surg 127(6):2270–2282

    CAS  Article  Google Scholar 

  28. 28.

    Maumus M, Sengenès C, Decaunes P, Zakaroff-Girard A, Bourlier V, Lafontan M, Galitzky J, Bouloumié A (2008) Evidence of in situ proliferation of adult adipose tissue-derived progenitor cells: influence of fat mass microenvironment and growth. J Clin EndocrinolMetab 93:4098–4106

    CAS  Article  Google Scholar 

  29. 29.

    Çakan D, Aydın S, Demir G, Başak K (2019) The effect of curcumin on healing in an animal nasal septal perforation model. Laryngoscope 129:E349–E354

    Article  Google Scholar 

  30. 30.

    Coleman SR (1997) Facial recontouring with lipostructure. Clin Plast Surg 24:347

    CAS  Article  Google Scholar 

  31. 31.

    Ghosh A, Kanthasamy A, Joseph J, Anantharam V, Srivastava P, Dranka BP, Kalyanaraman B, Kanthasamy A (2012) Anti-inflammatory and neuroprotective effects of an orally active apocynin derivative in pre-clinical models of Parkinson’s disease. J Neuroinflammation 9:241

    CAS  Article  Google Scholar 

  32. 32.

    Kinkade K, Streeter J, Miller FJ (2013) Inhibition of NADPH oxidase by apocynin attenuates progression of atherosclerosis. Int J Mol Sci 14(8):17017–17028

    Article  Google Scholar 

  33. 33.

    Joshi S, Saylor BT, Wang W, Peck AB, Khan SR (2012) Apocynin-treatment reverses hyperoxaluria induced changes in NADPH oxidase system expression in rat kidneys: a transcriptional study. PLoS ONE 7(10):47738

    Article  Google Scholar 

  34. 34.

    Pan L, Qian S (2018) Apocynin promotes neural function recovery and suppresses neuronal apoptosis by inhibiting Tlr4/NF-κB signaling pathway in a rat model of cerebral infarction. Int J Immunopathol Pharmacol 32:2058738418817700

    Article  Google Scholar 

  35. 35.

    Varghese J, Griffin M, Mosahebi A, Butler P (2017) Systematic review of patient factors affecting adipose stem cell viability and function: implications for regenerative therapy. Stem Cell Res. Ther 8(1):45

    Article  Google Scholar 

  36. 36.

    Nasir S, Aydin MA, Karahan N, Altuntaş S (2008) Fat tissue as a new vascular carrier for prefabrication in reconstructive surgery: experimental study in rats. J Plast Reconstr Aesthet Surg 61(7):799–806

    Article  Google Scholar 

  37. 37.

    Eto H, Kato H, Suga H, Aoi N, Doi K, Kuno S, Yoshimura K (2012) The fate of adipocytes after nonvascularized fat grafting: evidence of early death and replacement of adipocytes. Plast Reconstr Surg 129:1081–1092

    CAS  Article  Google Scholar 

  38. 38.

    Wang WZ, Fang XH, Williams SJ, Stephenson LL, Baynosa RC, Wong N, Khiabani KT, Zamboni WA (2013) Analysis for apoptosis and necrosis on adipocytes, stromal vascular fraction, and adipose derived stem cells in human lipoaspirates after liposuction. Plast Reconstr Surg 131(01):77–85

    Article  Google Scholar 

  39. 39.

    Yoshimura K, Eto H, Kato H, Doi K, Aoi N (2011) Manipulation of stem cells for adipose tissue repair/reconstruction. Regen Med 6(6s):33–41

    CAS  Article  Google Scholar 

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This study has no financial supporters. The authors thank Professor Abdullah Tuten for proof reading.

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Correspondence to Dogan Çakan.

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Ethical Approval

All applicable institutional and/or national guidelines for the care and use of animals were followed. The study was approved by Acibadem University Experimental Ethics Committee (decision date / no: 12.08.2015/50) and conducted in the Acibadem University Experimental Animal Application and Research Center.

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The study was conducted in Acıbadem University Experimental Animal Application and Research Center.

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Keskin, E.R., Çakan, D. The Effect of Apocynin on Fat Graft Survival. Aesth Plast Surg (2021).

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  • Animals
  • Apocynin
  • Adipose tissue / transplantation*
  • Graft survival / drug effects*
  • Rats