Facial Plast Surg 2022; 38(04): 419-427
DOI: 10.1055/a-1738-1194
Original Research

The Effect of Locally Delivered Apocynin on Fat Graft Survival in an Experimental Rat Animal Model

1   Department of Otorhinolaryngology, Istanbul University-Cerrahpasa Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
,
Sinem Eroğlu
2   Department of Aesthetic, Plastic and Reconstructive Surgery Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
,
Ekrem Ramazan Keskin
3   Department of Aesthetic, Plastic and Reconstructive Surgery Istanbul Rio Clinic, Istanbul, Turkey
› Author Affiliations
Funding None.

Abstract

We aimed to investigate the efficacy of locally delivered apocynin on fat graft survival in an experimental autologous fat grafting (AFG) model created in rats. Twenty-one Wistar albino male rats were included in this study. The 0.647 g mean weight grafts were harvested from the inguinal region and transferred to the nape of every rat. The subjects were randomly separated into three groups. Saline, dimethyl sulfoxide (DMSO), and apocynin, a dose of 20 mg/kg, solutions were applied once a day for 2 weeks. After 3 months, the rats were sacrificed. The evaluation of physical measurements (weight and volume) and survival rates of the grafts for volume and weight, the viable cell count (VC) with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and histopathological parameters were done. All biophysical parameters were found to be significantly higher in the apocynin group compared with other groups (p < 0.05). In the MTT test, the saline group was normalized to 100%. According to this, DMSO and apocynin groups' means were 106 and 163%, respectively. The VC was significantly higher in the apocynin group than the other groups (p < 0.05). The VC was significantly higher in the DMSO group than in the saline group (p < 0.05). No significant difference was found in other comparisons performed according to biophysical and histopathological parameters (p > 0.05). The locally delivered apocynin decreases fat graft volume loss in an experimental AFG model. Consequently, apocynin can be used as an effective substance to increase graft survival. The level of evidence was not available.

Ethical Statement

The study was conducted in Acıbadem University Experimental Animal Application and Research Center with the approval of Acıbadem University Local Ethics Committee (decision no: 12.08/51). All institutional and national guidelines for the care and use of laboratory animals were followed.


Contributions

Each of the authors has contributed to reading and approved this manuscript. The experiment was done by ERK and SC. The article was written by DC. This manuscript is original and it or any part of it has not been previously published, and it is not under consideration for publication elsewhere.




Publication History

Accepted Manuscript online:
12 January 2022

Article published online:
08 March 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Bohluli B, Bagheri SC, Consky EK. Fat grafting as an adjunct to facial rejuvenation procedures. Atlas Oral Maxillofac Surg Clin North Am 2018; 26 (01) 51-57
  • 2 Strong AL, Cederna PS, Rubin JP, Coleman SR, Levi B. The current state of fat grafting: a review of harvesting, processing, and injection techniques. Plast Reconstr Surg 2015; 136 (04) 897-912
  • 3 Abu-Ghname A, Perdanasari AT, Reece EM. Principles and applications of fat grafting in plastic surgery. Semin Plast Surg 2019; 33 (03) 147-154
  • 4 Hoppela E, Grönroos TJ, Saarikko AM. et al. Fat grafting can induce browning of white adipose tissue. Plast Reconstr Surg Glob Open 2018; 6 (06) e1804
  • 5 Sezgi̇n B, Özmen S. Fat grafting to the face with adjunctive microneedling: a simple technique with high patient satisfaction. Turk J Med Sci 2018; 48 (03) 592-601
  • 6 Guisantes E, Fontdevila J, Rodríguez G. Autologous fat grafting for correction of unaesthetic scars. Ann Plast Surg 2012; 69 (05) 550-554
  • 7 Minn KW, Min KH, Chang H, Kim S, Heo EJ. Effects of fat preparation methods on the viabilities of autologous fat grafts. Aesthetic Plast Surg 2010; 34 (05) 626-631
  • 8 MacRae JW, Tholpady SS, Ogle RC, Morgan RF. Ex vivo fat graft preservation: effects and implications of cryopreservation. Ann Plast Surg 2004; 52 (03) 281-282 , discussion 283
  • 9 Park B, Kong JS, Kang S, Kim YW. The effect of epidermal growth factor on autogenous fat graft. Aesthetic Plast Surg 2011; 35 (05) 738-744
  • 10 Por YC, Yeow VK, Louri N, Lim TK, Kee I, Song IC. Platelet-rich plasma has no effect on increasing free fat graft survival in the nude mouse. J Plast Reconstr Aesthet Surg 2009; 62 (08) 1030-1034
  • 11 Fraga MF, Helene Jr A, Nakamura F, Lellis RF, Kikuchi W, Esteban D. Comparative study of the integration and viability of autonomised and nonautonomised autologous fat tissue grafts–experimental model in rabbits. J Plast Reconstr Aesthet Surg 2008; 61 (09) 1044-1048
  • 12 Pu LL, Coleman SR, Cui X, Ferguson Jr RE, Vasconez HC. Cryopreservation of autologous fat grafts harvested with the Coleman technique. Ann Plast Surg 2010; 64 (03) 333-337
  • 13 Grewal N, Yacomotti L, Melkonyan V, Massey M, Bradley JP, Zuk PA. Freezing adipose tissue grafts may damage their ability to integrate into the host. Connect Tissue Res 2009; 50 (01) 14-28
  • 14 Kim SK, Yang JY, Kim CW, Baek SH, Kim U, Hwang E. The effect of hyaluronidase on the fat graft. J Craniofac Surg 2020; 31 (03) 618-621
  • 15 Cin B, Ciloglu NS, Omar S, Terzi NK. Effect of rosmarinic acid and alcohol on fat graft survival in rat model. Aesthetic Plast Surg 2020; 44 (01) 177-185
  • 16 Laddha AP, Kulkarni YA. NADPH oxidase: a membrane-bound enzyme and its inhibitors in diabetic complications. Eur J Pharmacol 2020; 881: 173206
  • 17 Cui H, Kong Y, Zhang H. Oxidative stress, mitochondrial dysfunction, and aging. J Signal Transduct 2012; 2012: 646354
  • 18 Stefanska J, Pawliczak R. Apocynin: molecular aptitudes. Mediators Inflamm 2008; 2008: 106507
  • 19 Heumüller S, Wind S, Barbosa-Sicard E. et al. Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. Hypertension 2008; 51 (02) 211-217
  • 20 Riganti C, Costamagna C, Bosia A, Ghigo D. The NADPH oxidase inhibitor apocynin (acetovanillone) induces oxidative stress. Toxicol Appl Pharmacol 2006; 212 (03) 179-187
  • 21 Vejrazka M, Mícek R, Stípek S. Apocynin inhibits NADPH oxidase in phagocytes but stimulates ROS production in non-phagocytic cells. Biochim Biophys Acta 2005; 1722 (02) 143-147
  • 22 Du ZD, Yu S, Qi Y. et al. NADPH oxidase inhibitor apocynin decreases mitochondrial dysfunction and apoptosis in the ventral cochlear nucleus of D-galactose-induced aging model in rats. Neurochem Int 2019; 124: 31-40
  • 23 Keskin ER, Çakan D. The effect of apocynin on fat graft survival. Aesthetic Plast Surg 2021; 45 (04) 1843-1852
  • 24 Alley MC, Scudiero DA, Monks A. et al. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res 1988; 48 (03) 589-601
  • 25 Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res 1987; 47 (04) 936-942
  • 26 Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007; 39 (02) 175-191
  • 27 International Society of Aesthetic Plastic Surgery. Global Survey Results (2019). . Accessed April 29, 2021 https://www.isaps.org/wp-content/uploads/2020/12/Global-Survey-2019.pdf
  • 28 Yuksel E, Weinfeld AB, Cleek R. et al. 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 2000; 105 (05) 1712-1720
  • 29 Ayhan M, Senen D, Adanali G, Görgü M, Erdoğan B, Albayrak B. Use of beta blockers for increasing survival of free fat grafts. Aesthetic Plast Surg 2001; 25 (05) 338-342
  • 30 Temiz G, Sirinoglu H, Yesiloglu N, Filinte D, Kaçmaz C. Effects of deferoxamine on fat graft survival. Facial Plast Surg 2016; 32 (04) 438-443
  • 31 Medina III MA, Nguyen JT, Kirkham JC. et al. Polymer therapy: a novel treatment to improve fat graft viability. Plast Reconstr Surg 2011; 127 (06) 2270-2282
  • 32 Gillis J, Gebremeskel S, Phipps KD. et al. Effect of n-acetylcysteine on adipose-derived stem cell and autologous fat graft survival in a mouse model. Plast Reconstr Surg 2015; 136 (02) 179e-188e
  • 33 Medina MA, Lee JH, Kirkham JC, McCormack MC, Randolph MA, Austen WG. Fat grafting, ischemia repurfusion, apoptosis, antioxidants. J Surg Res 2011; 165 (02) 323-328
  • 34 Shih L, Davis MJ, Winocour SJ. The science of fat grafting. Semin Plast Surg 2020; 34 (01) 5-10
  • 35 Peer LA. Loss of weight and volume in human fat grafts with postulation of a “Cell Survival Theory”. Plast Reconstr Surg 1950; 5: 217-230
  • 36 Oranges CM, Striebel J, Tremp M. et al. The preparation of the recipient site in fat grafting: a comprehensive review of the preclinical evidence. Plast Reconstr Surg 2019; 143 (04) 1099-1107
  • 37 Espiritu DJ, Mazzone T. Oxidative stress regulates adipocyte apolipoprotein e and suppresses its expression in obesity. Diabetes 2008; 57 (11) 2992-2998
  • 38 Coleman SR. Facial recontouring with lipostructure. Clin Plast Surg 1997; 24 (02) 347-367
  • 39 Maumus M, Sengenès C, Decaunes P. et al. Evidence of in situ proliferation of adult adipose tissue-derived progenitor cells: influence of fat mass microenvironment and growth. J Clin Endocrinol Metab 2008; 93 (10) 4098-4106
  • 40 Çakan D, Aydın S, Demir G, Başak K. The effect of curcumin on healing in an animal nasal septal perforation model. Laryngoscope 2019; 129 (10) E349-E354
  • 41 Ghosh A, Kanthasamy A, Joseph J. et al. Anti-inflammatory and neuroprotective effects of an orally active apocynin derivative in pre-clinical models of Parkinson's disease. J Neuroinflammation 2012; 9: 241
  • 42 Kinkade K, Streeter J, Miller FJ. Inhibition of NADPH oxidase by apocynin attenuates progression of atherosclerosis. Int J Mol Sci 2013; 14 (08) 17017-17028
  • 43 Joshi S, Saylor BT, Wang W, Peck AB, Khan SR. Apocynin-treatment reverses hyperoxaluria induced changes in NADPH oxidase system expression in rat kidneys: a transcriptional study. PLoS One 2012; 7 (10) e47738
  • 44 Pan L, Qian S. 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 2018;32:2058738418817700
  • 45 Savla SR, Laddha AP, Kulkarni YA. Pharmacology of apocynin: a natural acetophenone. Drug Metab Rev 2021; 53 (04) 542-562
  • 46 Varghese J, Griffin M, Mosahebi A, Butler P. Systematic review of patient factors affecting adipose stem cell viability and function: implications for regenerative therapy. Stem Cell Res Ther 2017; 8 (01) 45
  • 47 Nasir S, Aydin MA, Karahan N, Altuntaş S. Fat tissue as a new vascular carrier for prefabrication in reconstructive surgery: experimental study in rats. J Plast Reconstr Aesthet Surg 2008; 61 (07) 799-806
  • 48 Eto H, Kato H, Suga H. et al. The fate of adipocytes after nonvascularized fat grafting: evidence of early death and replacement of adipocytes. Plast Reconstr Surg 2012; 129 (05) 1081-1092
  • 49 Suga H, Eto H, Aoi N. et al. Adipose tissue remodeling under ischemia: death of adipocytes and activation of stem/progenitor cells. Plast Reconstr Surg 2010; 126 (06) 1911-1923
  • 50 Mecott GA, Gonzalez IZ, Montes de Oca R. et al. Effect of decantation time on viability and apoptosis in adipocytes after liposuction. Aesthetic Plast Surg 2019; 43 (01) 228-232
  • 51 Coban YK, Ciralik H. The effects of increased ischemic times on adipose tissue: a histopathologic study using the epigastric flap model in rats. Aesthetic Plast Surg 2007; 31 (05) 570-573
  • 52 Mecott GA, Cueto-Ramos RG, González-Martínez A. et al. Determination of the ratio of the decantation time and the separation of components in lipoaspirate. Ann Plast Surg 2020; 85 (05) e7-e11
  • 53 Wang WZ, Fang XH, Williams SJ. et al. Analysis for apoptosis and necrosis on adipocytes, stromal vascular fraction, and adipose-derived stem cells in human lipoaspirates after liposuction. Plast Reconstr Surg 2013; 131 (01) 77e-85e
  • 54 Mashiko T, Yoshimura K. How does fat survive and remodel after grafting?. Clin Plast Surg 2015; 42 (02) 181-190
  • 55 Hu L, Zhang Y, Lim PS. et al. Apocynin but not L-arginine prevents and reverses dexamethasone-induced hypertension in the rat. Am J Hypertens 2006; 19 (04) 413-418
  • 56 Tan YC, Abdul Sattar M, Ahmeda AF. et al. Apocynin and catalase prevent hypertension and kidney injury in cyclosporine A-induced nephrotoxicity in rats. PLoS One 2020; 15 (04) e0231472
  • 57 Liao HT, Marra KG, Rubin JP. Application of platelet-rich plasma and platelet-rich fibrin in fat grafting: basic science and literature review. Tissue Eng Part B Rev 2014; 20 (04) 267-276