Keywords
flavonoids
bergamot
surgical wounds
hyaluronic acid
How to Cite
Abstract
Objective: Haemorrhoidal disease (HD) is a very diffuse anorectal condition that involves a large part of the population, both male and female of every age. Among the procedures proposed to treat HD, conventional excisional surgery remains one of the most performed. Milligan-Morgan (MM) technique is one of the most used haemorrhoidectomy techniques. In this technique, the wounds are left open and re-epithelialization requires almost 3-5 weeks, in which patients generally experience pain and intense discomfort improving over the weeks.
Methods: The aim of this study was to evaluate the effect of topic administration of Benebeo Gel®, mainly composed by bergamot-derived flavonoids and hyaluronic acid, on post-operative wound healing after open MM haemorrhoidectomy. An observational prospective study was carried out, involving 205 patients aged between 18 and 75.
Results and Conclusion: The results after 2 weeks of treatment seem to be promising with a very good clinical outcome and patient satisfaction within 1 month.
References
Riss S, Weiser FA, Schwameis K, Riss T, Mittlböck M, Steiner G, Stift A. The prevalence of hemorrhoids in adults. Int J Colorectal Dis 2012; 27(2): 215-220. https://doi.org/10.1007/s00384-011-1316-3
Sheikh P, Régnier C, Goron F, Salmat G. The prevalence, characteristics and treatment of hemorrhoidal disease: Results of an international web-based survey. J Comp Eff Res 2020; 9(17): 1219-1232. https://doi.org/10.2217/cer-2020-0159
Gallo G, Sacco R, Sammarco G. Epidemiology of hemorrhoidal disease. Coloproctology 2018; 2: 3-7. https://doi.org/10.1007/978-3-319-53357-5_1
Lohsiriwat V. Hemorrhoids: From basic pathophysiology to clinical management. World J Gastroenterol 2012; 18(17): 2009-2017. https://doi.org/10.3748/wjg.v18.i17.2009
Romano FM, Sciaudone G, Canonico S, Selvaggi F, Pellino G. Scoring system for haemorrhoidal disease. Rev Rec Clin Trials 2021; 16(1): 96-100. https://doi.org/10.2174/1574887115666200319162033
Goligher JC, Duthie HL, Nixon HH. Surgery of the Anus, Rectum, and Colon. 3rd ed. London: Baillière Tindall 1975.
Van Tol RR, Kimman ML, Melenhorst J, Stassen LPS, Dirksen CD, Breukink SO. European society of coloproctology core outcome set for haemorrhoidal disease: an international Delphi study among healthcare professionals. Colorectal Dis 2019; 21: 570-580. https://doi.org/10.1111/codi.14553
Fargo MV, Latimer KM. Evaluation and management of common anorectal conditions. Am Fam Physician 2012; 85(6): 624-630.
Serra R, Gallelli L, Grande R, Amato B, De Caridi G, Sammarco G, et al. Hemorrhoids and matrix metalloproteinases: A multicenter study on the predictive role of biomarkers. Surgery 2016; 159: 487-494. https://doi.org/10.1016/j.surg.2015.07.003
Cocorullo G, Tutino R, Falco N, Licari L, Orlando G, Fontana T, Raspanti C, Salamone G, Scerrino G, Gallo G, et al. The non-surgical management for hemorrhoidal disease. A systematic review. G Chiral 2017; 38: 5-14. https://doi.org/10.11138/gchir/2017.38.1.005
Nicholson TJ, Armstrong D. Topical metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing. Dis Colon Rectum 2004; 47: 711-716. https://doi.org/10.1007/s10350-003-0129-z
Karanlik H, Akturk R, Camlica H, Asoglu O. The effect of glyceryl trinitrate ointment on posthemorrhoidectomy pain and wound healing: results of a randomized, double-blind, placebo-controlled study. Dis Colon Rectum 2009; 52: 280-285. https://doi.org/10.1007/DCR.0b013e31819c98a7
Gupta PJ, Heda PS, Kalaskar S, Tamaskar VP. Topical sucralfate decreases pain after hemorrhoidectomy and improves healing: a randomized, blinded, controlled study. Dis Colon Rectum 2008; 51: 231-234. https://doi.org/10.1007/s10350-007-9092-4
Ala S, Alvandipour M, Saeedi M, Hamidian M, Shiva A, Rahmani N, Faramarzi F. Effects of topical atorvastatin (2%) on posthemorrhoidectomy pain and wound healing: a randomized double-blind placebo-controlled clinical trial. World J Surg 2017; 41: 596-602. https://doi.org/10.1007/s00268-016-3749-x
Duman N, Duman R, Tosun M, Akıcı M, Göksel E, Gökçe B, Alagöz O. Topical folinic acid enhances wound healing in rat model. Adv Med Sci 2018; 63: 347-352. https://doi.org/10.1016/j.advms.2018.04.011
Indian medicine.nic.in [homepage on the internet] Available from: http://indianmedicine.nic.in/showfi le.asp?lid=44 [Last accessed on 2013 Oct 28].
Hashempur MH, Khademi F, Rahmanifard M, Zarshenas MM. An Evidence-Based Study on Medicinal Plants for Hemorrhoids in Medieval Persia. J Evid Based Complement Altern Med 2017; 22: 969. https://doi.org/10.1177/2156587216688597
Andarkhor P, Sadeghi A, Khodadoost M, Kamalinejad M, Gachkar L, Abdi S, Zargaran A. Effects of Terminalia chebula Retz. in treatment of hemorrhoids: A double-blind randomized placebo-controlled clinical trial. Eur J Integr Med 2019; 30: 100935. https://doi.org/10.1016/j.eujim.2019.100935
Xu X, Li X, Zhang L, Liu Z, Pan Y, Chen D, Bin D, Deng Q, Sun Y, Hoffman RM, et al. Enhancement of wound healing by the traditional Chinese medicine herbal mixture Sophora flavescens in a rat model of perianal ulceration. In Vivo 2017; 31: 543-549. https://doi.org/10.21873/invivo.11092
Dönmez C, Yalçın FN, Boyacıoğlu Ö, Korkusuz P, Akkol EK, Nemutlu E, Balaban YH, Çalışkan UK. From nutrition to medicine: Assessing hemorrhoid healing activity of Solanum melongena L. via in vivo experimental models and its major chemicals. J Ethnopharmacol 2020; 261: 113143. https://doi.org/10.1016/j.jep.2020.113143
Mihai PD, Seremet CO, Nitulescu G, Ivopol M, Sevastre A-S, Negres S, Ivopol G, Nitulescu MG, Olaru TO. Evaluation of natural extracts in animal models of pain and inflammation for a potential therapy of hemorrhoidal disease. Sci Pharm 2019; 87: 14. https://doi.org/10.3390/scipharm87020014
Porwal A, Kundu GC, Bhagwat G, Butti R. Polyherbal formulation Anoac H suppresses the expression of RANTES and VEGF for the management of bleeding hemorrhoids and fistula. Mol Med Rep 2021; 24(4): 1-8. https://doi.org/10.3892/mmr.2021.12376
Porwal A, Kundu GC, Bhagwat G, Butti R. Herbal medicine AnoSpray suppresses proinflammatory cytokines COX-2 and RANTES in the management of hemorrhoids, acute anal fis-sures and perineal wounds. Exp Ther Med 2022; 23(1): 1-9. https://doi.org/10.3892/etm.2021.11009
Dimitroulopoulos D, Tsamakidis K, Xinopoulos D, Karaitianos I, Fotopoulou A, Paraskevas E. Prospective, randomized, controlled, observer-blinded trial of combined infrared photocoagulation and micronized purified flavonoid fraction versus each alone for the treatment of hemorrhoidal disease. Clin Therapeut 2005; 27(6): 746-754. https://doi.org/10.1016/j.clinthera.2005.06.016
Serventi A. The Italian paradox of flavonoid use for hemorrhoids. Techn Coloproctol 2020; 24(6): 613-613. https://doi.org/10.1007/s10151-020-02217-6
Fratianni F, Cozzolino A, De Feo V, Coppola R, Ombra MN, Nazzaro F. Polyphenols, antioxidant, antibacterial, and biofilm inhibitory activities of peel and pulp of Citrus medica L., Citrus bergamia, and Citrus medica cv. Salò Cultivated in Southern Italy. Molecules 2019; 24(24): 4577. https://doi.org/10.3390/molecules24244577
Aggrawal K, Satija N, Dasgupta G, Dasgupta P, Nain P, Sahu AR. Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study. J Ayurveda Integr Med 2014; 5(2): 117. https://doi.org/10.4103/0975-9476.131732
Surjushe A, Resham V, Saple DG. Aloe Vera: A Short Review. Indian J Dermatology PMC Web 2008; 53: 163-166. https://doi.org/10.4103/0019-5154.44785
Riaz S, Hussain S, Syed SK, Anwar R. Chemical characteristics and therapeutic potentials of Aloe vera. Magnesium 2021; 1(11): 48.
Eshghi F, Hosseinimehr SJ, Rahmani N, Khademloo M, Norozi MS, Hojati O. Effects of Aloe vera cream on posthemor rhoidectomy pain and wound healing: results of a randomized, blind, placebo-control study. J Altern Complement Med 2010; 16: 647-650. https://doi.org/10.1089/acm.2009.0428
Sturiale A, Gallo G, Brusciano L, Cacace C, Cafaro D, Porzio FC, Naldini G. Safety and efficacy of proctosoll allevia in the management of haemorrhoidal disease in adults: a prospective randomized clinical trial. Rev Recent Clin Trials 2020; 15: 152-159. https://doi.org/10.2174/1574887115666200421110107
Ibrahim S, Joddar B, Craps M, Ramamurthi A. A surface-tethered model to assess size-specific effects of hyaluronan (HA) on endothelial cells. Biomaterials 2007; 28: 825-835. https://doi.org/10.1016/j.biomaterials.2006.09.030
de Oliveira JD, Carvalho LS, Gomes AM, Queiroz LR, Magalhães BS, Parachin NS. Genetic basis for hyper production of hyaluronic acid in natural and engineered microorganisms. Microb Cell Fact 2016; 15: 11. https://doi.org/10.1186/s12934-016-0517-4
Kogan G, Soltes L, Stern R, Gemeiner P. Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications. Biotechnol Lett 2007; 29: 17-25. https://doi.org/10.1007/s10529-006-9219-z
Jiang D, Liang J, Noble PW. Hyaluronan as an immune regulator in human diseases. Physiol Rev 2011; 91(1): 221-264. https://doi.org/10.1152/physrev.00052.2009
Saturnino C, Sinicropi MS, Parisi OI, Iacopetta D, Popolo A, Marzocco S, Caruso A, Cappello AR, Longo P, Puoci F. Acetylated hyaluronic acid: Enhanced bioavailability and biological studies. BioMed Res Int 2014; 921549. https://doi.org/10.1155/2014/921549
Altomare DF, Giannini I. Pharmacological treatment of hemorrhoids: a narrative review. Exp Opin Pharmacother 2013; 14(17): 2343-2349. https://doi.org/10.1517/14656566.2013.836181
Gallo G, Martellucci J, Sturiale AE, Clerico G, Milito G, Marino F, Cocorullo C, Giordano P, Mistrangelo M, Trompetto M. Consensus statement of the Italian society of colorectal surgery (SICCR): management and treatment of hemorrhoidal disease. Tech Coloproctol 2020; 24(2): 145-164. https://doi.org/10.1007/s10151-020-02149-1
Altomare DF, Picciariello A, Pecorella G, Milito G, Naldini G, Amato A, Ratto C, Perinotti R. Surgical management of haemorrhoids: an Italian survey of over 32 000 patients over 17 years. Color Dis 2018; 20(12): 1117-1124. https://doi.org/10.1111/codi.14339
Cintron J, Abcarian AM, Abcarian H, Makiewicz K, Brand MI. Hemorrhoids. In Complications of Anorectal Surgery, Springer, Cham. 2017; pp. 61-108. https://doi.org/10.1007/978-3-319-48406-8_4
Simillis C, Thoukididou SN, Slesser AAP, Rasheed S, Tan E, Tekkis PP. Systematic review and network meta-analysis comparing clinical outcomes and effectiveness of surgical treatments for haemorrhoids. Br J Surg 2015; 102(13): 1603-1618. https://doi.org/10.1002/bjs.9913
Simoglou C, Simoglou L, Babalis D, Gimnopoulos D. Milligan—Morgan haemorrhoidectomy — Complications. Hell J Surg 2014; 86(2): 68-71. https://doi.org/10.1007/s13126-014-0100-6
Heyerick L, Van de Putte D, De Visschere M, Pattyn P, Tate D, Van Vlierberghe H, De Looze D. Thunderbeat-Assisted Hemorrhoidectomy in Symptomatic Prolapsing Hemorrhoids: A Pilot Trial. In XXXth Belgian Week of Gastroenterology 2018; 95-96.
Gerbershagen HJ, Aduckathil S, van Wijck AJM, Peelen LM, Kalkman CJ, Meissner W. Pain Intensity on the First Day after Surgery: A Prospective Cohort Study Comparing 179 Surgical Procedures. Anesthesiol. J Am Soc Anesthesiol 2013; 118: 934-944. https://doi.org/10.1097/ALN.0b013e31828866b3
Jacobs D. Clinical practice. Hemorrhoids. N Engl J Med 2014; 371: 944-951. https://doi.org/10.1056/NEJMcp1204188
Abo-Hashem A, Sarhan A, Aly A. Harmonic Scalpel compared with bipolar electro-cautery hemorrhoidectomy: A randomized controlled trial. Int J Surg 2010; 8: 243-247. https://doi.org/10.1016/j.ijsu.2010.01.010
Naldini G, Caminati F, Sturiale A, Fabiani B, Cafaro D, Menconi C, Mascagni D, Porzio FC. Improvement in Hemorrhoidal Disease Surgery Outcomes Using a New Anatomical/Clinical-Therapeutic Classification (A/CTC). Surg J 2020; 6(3): e145-e152. https://doi.org/10.1055/s-0040-1712542
Medina-Gallardo A, Curbelo-Peña Y, De Castro X, Roura-Poch P, Roca-Closa J, De Caralt-Mestres E. Is the severe pain after Milligan-Morgan hemorrhoidectomy still currently remaining a major postoperative problem despite being one of the oldest surgical techniques described? A case series of 117 consecutive patients. Int J Surg Case Rep 2017; 30: 73-75. https://doi.org/10.1016/j.ijscr.2016.11.018
Cafaro D, Sturiale A, Fortuna V, Sinicropi MS, Naldini G. Clinical effect of the bergamot-derived gel (Benebeo gel®) associated with mesalazine for the treatment of anitis and proctitis. Trends Gen Pract 2018; 1(2): 1-3. https://doi.org/10.15761/TGP.1000110
Cafaro D, Celedon F, Sturiale A, Sinicropi MS. Innovative results in the treatment of inespecific anusitis-proctitis with the use of bergamot gel (Benebeo gel)®. Insights Clin Cell Immunol 2019; 3(1): 20-24. https://doi.org/10.29328/journal.icci.1001011
Navarra M, Mannucci C, Delbò M, Calapai G. Citrus bergamia essential oil: from basic research to clinical application. Front Pharmacol 2015; 6: 36. https://doi.org/10.3389/fphar.2015.00036
Mannucci C, Navarra M, Calapai F, Squeri R, Gangemi S, Calapai G. Clinical pharmacology of Citrus bergamia: a systematic review. Phytother Res 2017; 31(1): 27-39. https://doi.org/10.1002/ptr.5734
Mandalari G, Bennett R, Bisignano G, Trombetta D, Saija A, Faulds C, Gasson M, Narbad A. Antimicrobial activity of flavonoids extracted from bergamot (Citrus bergamia Risso) peel, a byproduct of the essential oil industry. J Appl Microbiol 2007; 103: 2056-2064. https://doi.org/10.1111/j.1365-2672.2007.03456.x
Salerno R, Casale F, Calandruccio C, Procopio A. Characterization of flavonoids in Citrus bergamia (Bergamot) polyphenolic fraction by liquid chromatography-high resolution mass spectrometry (LC/HRMS). Pharma Nutrition 2016; 4: S1-S7. https://doi.org/10.1016/j.phanu.2015.10.001
Graziano AC, Cardile V, Crasci L, Caggia S, Dugo P, Bonina F, Panico A. Protective effects of an extract from Citrus bergamia against inflammatory injury in interferon-gamma and histamine exposed human keratinocytes. Life Sci 2012; 90: 968-974. https://doi.org/10.1016/j.lfs.2012.04.043
Bruno A, Pandolfo G, Crucitti M, Cedro C, Zoccali RA, Muscatello MRA. Bergamot polyphenolic fraction supplementation improves cognitive functioning in schizophrenia: data from an 8-week, open-label pilot study. J Clin Psychopharmacol 2017; 37(4): 468-471. https://doi.org/10.1097/JCP.0000000000000730
Navarra M, Ferlazzo N, Cirmi S, Trapasso E, Bramanti P, Lombardo GE, Minciullo PL, Calapai G, Gangemi S. Effects of bergamot essential oil and its extractive fractions on SH-SY5Y human neuroblastoma cell growth. J Pharm Pharmacol 2015; 67: 1042-1053. https://doi.org/10.1111/jphp.12403
Impellizzeri D, Bruschetta G, di Paola R, Ahmad A, Campolo M, Cuzzocrea S, Esposito E, Navarra M. The anti-inflammatory and antioxidant effects of bergamot juice extract (BJe) in an experimental model of inflammatory bowel disease. Clin Nutr 2015; 34: 1146-1154. https://doi.org/10.1016/j.clnu.2014.11.012
Man MQ, Yang B, Elias PM. Benefits of hesperidin for cutaneous functions. Evid. Based Complement. Alternat Med 2019; 2019: 2676307. https://doi.org/10.1155/2019/2676307
Risitano R, Curro M, Cirmi S, Ferlazzo N, Campiglia P, Caccamo D, Ientile R, Navarra M. Flavonoid fraction of bergamot juice reduces LPS-induced inflammatory response through SIRT1-mediated NF-κB inhibition in THP-1 monocytes. PLoS ONE 2014; 9: e107431. https://doi.org/10.1371/journal.pone.0107431
Lorzadeh E, Ramezani-Jolfaie N, Mohammadi M. The effect of hesperidin supplementation on inflammatory markers in human adults: a systematic review and meta-analysis of randomized controlled clinical trials. Chem Biol Interact 2019; 307: 8-15. https://doi.org/10.1016/j.cbi.2019.04.016
Tripoli E, Guardia ML, Giammanco S, Majo DD, Giammanco M. Citrus flavonoids: molecular structure, biological activity and nutritional properties: a review. Food Chem 2007; 104: 466-479. https://doi.org/10.1016/j.foodchem.2006.11.054
Nisticò S, Ehrlich J, Gliozzi M, Maiuolo J, Del Duca E, Muscoli C, Mollace V. Telomere and Telomerase Modulation by Bergamot Polyphenolic Fraction in Experimental Photoageing in Human Keratinocytes. J Biol Regul Homeost Agents 2015; 29: 723-728.
Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Adv Nutrit 2014; 5(4): 404-417. https://doi.org/10.3945/an.113.005603
Ittiudomrak T, Puthong S, Roytrakul S, Chanchao C. α-mangostin and apigenin induced cell cycle arrest and programmed cell death in SKOV-3 ovarian cancer cells. Toxicol Res 2019; 35: 167-179. https://doi.org/10.5487/TR.2019.35.2.167
Yue S, Xue N, Li H, Huang B, Chen Z, Wang X. Hepatoprotective effect of apigenin against liver injury via the non-canonical NF-κB pathway in vivo and in vitro. Inflammation 2020; 43: 1634-1648. https://doi.org/10.1007/s10753-020-01238-5
Patil RH, Babu RL, Naveen Kumar M, Kiran Kumar KM, Hegde SM, Nagesh R, Ramesh GT, Sharma SC. Anti-inflammatory effect of apigenin on LPS-induced pro-inflammatory mediators and AP-1 factors in human lung epithelial cells. Inflammation 2016; 39: 138-147. https://doi.org/10.1007/s10753-015-0232-z
Zhang Y, Wang J, Cheng X, Yi B, Zhang X, Li Q. Apigenin induces dermal collagen synthesis via smad2/3 signaling pathway. Eur J Histochem 2015; 59: 2467. https://doi.org/10.4081/ejh.2015.2467
Hwang YP, Oh KN, Yun HJ, Jeong HG. The flavonoids apigenin and luteolin suppress ultraviolet A-induced matrix metalloproteinase-1 expression via MAPKs and AP-1-dependent signaling in HaCaT cells. J Dermatol Sci 2011; 61: 23-31. https://doi.org/10.1016/j.jdermsci.2010.10.016
Salehi B, Fokou PVT, Sharifi-Rad M, Zucca P, Pezzani R, Martins N, Sharifi-Rad J. The therapeutic potential of naringenin: a review of clinical trials. Pharmaceuticals 2019; 12(1): 11. https://doi.org/10.3390/ph12010011
Tripathi A, Awasthi H, Rokaya DB, Srivastava D, Srivastava V. Antimicrobial and wound healing potential of dietary flavonoid naringenin. Nat Prod J 2019; 9(1): 61-68. https://doi.org/10.2174/2210315508666180802104630
Xu J, Ma L, Fu P. Eriocitrin attenuates ischemia reperfusion-induced oxidative stress and inflammation in rats with acute kidney injury by regulating the dual-specificity phosphatase 14 (DUSP14)-mediated Nrf2 and nuclear factor-κB (NF-κB) pathways. Ann Translat Med 2021; 9(4). https://doi.org/10.21037/atm-21-337
Guo G, Shi W, Shi F, Gong W, Li F, Zhou G, She J. Anti-inflammatory effects of eriocitrin against the dextran sulfate sodium-induced experimental colitis in murine model. J Biochem Mol Toxicol 2019; 33: e22400. https://doi.org/10.1002/jbt.22400
Jing Y, Wu X, Jiang H, Wang R. Nephroprotective effects of eriocitrin via alleviation of oxidative stress and DNA damage against cisplatin-induced renal toxicity. Turk J Biochem 2020; 45(4): 381-388. https://doi.org/10.1515/tjb-2019-0399
Yuan C, Chen G, Jing C, Liu M, Liang B, Gong G, Yu M. Eriocitrin, a dietary flavonoid suppressed cell proliferation, induced apoptosis through modulation of JAK2/STAT3 and JNK/p38 MAPKs signaling pathway in MCF‐7 cells. J Biochem Mol Toxicol 2021; e22943. https://doi.org/10.1002/jbt.22943
Liu J, Huang H, Huang Z, Ma Y, Zhang L, He Y, Li D, Liu W, Goodin S, Zhang K, et al. Eriocitrin in combination with resveratrol ameliorates LPS-induced inflammation in RAW264.7 cells and relieves TPA-induced mouse ear edema. J Funct Foods 2019; 56: 321-332. https://doi.org/10.1016/j.jff.2019.03.008
Miyake Y, Suzuki E, Ohya S, Fukumoto S, Hiramitsu M, Sakaida K, Osawa T, Furuichi Y. Lipid-lowering effect of eriocitrin, the main flavonoid in lemon fruit, in rats on a high-fat and high-cholesterol diet. J Food Sci 2006; 71: S633-S637. https://doi.org/10.1111/j.1750-3841.2006.00192.x
Marhuenda J, Cerdá B, Villaño D, Galindo A, Zafrilla P. Citrus and Health. In Citrus—Health Benefits and Production Technology; IntechOpen: Rijeka, Croatia 2019; pp. 1-16. ISBN 9781626239777. https://doi.org/10.5772/intechopen.79283
de Souza Carvalho J, Ramadan D, de Paiva Gonçalves V, Maquera-Huacho PM, Assis RP, Lima TFO, Brunetti IL, Palomari Spolidorio DM, Cesar T, Mathey JA, et al. Impact of citrus flavonoid supplementation on inflammation in lipopolysaccharide-induced periodontal disease in mice. Food Funct 2021; 12: 5007-5017. https://doi.org/10.1039/D0FO03338C
Alghamdi S. Antinociceptive effect of the citrus flavonoid eriocitrinon postoperative pain conditions. J Pain Res 2020; 13: 805. https://doi.org/10.2147/JPR.S250391
Sudha PN, Rose MH. Beneficial effects of hyaluronic acid. Adv Food Nutr Res 2014; 72: 137-176. https://doi.org/10.1016/B978-0-12-800269-8.00009-9
Ortonne JP. A controlled study of the activity of hyaluronic acid in the treatment of venous leg ulcers. J Dermatolog Treat 1996; 7(2): 75-81. https://doi.org/10.3109/09546639609089533
Tagliagambe M, Elstrom TA, Ward DB. Hyaluronic acid sodium salt 0.2% gel in the treatment of a recalcitrant distal leg ulcer: a case report. J Clin Aesth Dermatol 2017; 10(11): 49.
Jiang D, Liang J, Noble PW. Hyaluronan in tissue injury and repair. Annu Rev Cell Dev Biol 2007; 23: 435-461. https://doi.org/10.1146/annurev.cellbio.23.090506.123337
Niu Y, Galluzzi M. Hyaluronic acid/collagen nanofiber tubular scaffolds support endothelial cell proliferation, phenotypic shape and endothelialization. Nanomaterials 2021; 11(9): 2334. https://doi.org/10.3390/nano11092334
Wang CC, Wang CT, Chou WC, Kao CL, Tsai KL. Hyaluronic acid injection reduces inflammatory and apoptotic markers through modulation of AKT by repressing the oxidative status of neutrophils from osteoarthritic synovial fluid. Int J Biol Macromol 2020; 165: 2765-2772. https://doi.org/10.1016/j.ijbiomac.2020.10.154
Kwon SH, Park KC. Antioxidants as an Epidermal Stem Cell Activator. Antioxidants 2020; 9(10): 958. https://doi.org/10.3390/antiox9100958
Campo GM, Avenoso A, Campo S, D’Ascola A, Ferlazzo AM, Calatroni A. The antioxidant and antifibrogenic effects of the glycosaminoglycans hyaluronic acid and chondroitin-4-sulphate in a subchronic rat model of carbon tetrachloride-induced liver fibrogenesis. Chem Biol Interact 2004; 148: 125-138. https://doi.org/10.1016/j.cbi.2004.05.004
Halicka HD, Mitlitski V, Heeter J, Balazs EA, Darzynkiewicz Z. Attenuation of the oxidative burst-induced DNA damage in human leukocytes by hyaluronan. Int J Mol Med 2009; 23: 695-699. https://doi.org/10.3892/ijmm_00000182
Foschi D, Castoldi L, Radaelli E, Abelli P, Calderini G, Rastrelli A, Mariscotti C, Marazzi M, Trabucchi E. Hyaluronic acid prevents oxygen free-radical damage to granulation tissue: A study in rats. Int J Tissue React 1990; 12: 333-339.
Trabucchi E, Pallotta S, Morini M, Corsi F, Franceschini R, Casiraghi A, Pravettoni A, Foschi D, Minghetti P. Low molecular weight hyaluronic acid prevents oxygen free radical damage to granulation tissue during wound healing. Int J Tissue React 2002; 24: 65-71.
Ke C, Sun L, Qiao D, Wang D, Zeng X. Antioxidant acitivity of low molecular weight hyaluronic acid. Food Chem Toxicol 2011; 49: 2670-2675. https://doi.org/10.1016/j.fct.2011.07.020
Kanitakis J, Ramirez-Bosca A, Reano A, Viac J, Roche P, Thivolet J. Filaggrin expression in normal and pathological skin. A marker of keratinocyte differentiation. Virchows Arch A Pathol Anat Histopathol 1988; 412: 375-382. https://doi.org/10.1007/BF00750265
Voigt J, Driver VR. Hyaluronic acid derivatives and their healing effect on burns, epithelial surgical wounds, and chronic wounds: a systematic review and meta-analysis of randomized controlled trials. Wound Repair Regen 2012; 20: 317-331. https://doi.org/10.1111/j.1524-475X.2012.00777.x
Neuman MG, Nanau RM, Oruña-Sanchez L, Coto G. Hyaluronic acid and wound healing. J Pharm Pharm Sci 2015; 18: 53-60. https://doi.org/10.18433/J3K89D
Cho JR, Lee MH, Oh HK, Kim H, Kweon DK, Kang SM, Kim BK, Heo CY, Kim DW, Kang SB. Efficacy of hyaluronic acid film on perianal wound healing in a rat model. Ann Surg Treat Res 2021; 101(4): 206. https://doi.org/10.4174/astr.2021.101.4.206
Altman R, Bedi A, Manjoo A, Niazi F, Shaw P, Mease P. Anti-inflammatory effects of intra-articular hyaluronic acid: a systematic review. Cartilage 2019; 10(1): 43-52. https://doi.org/10.1177/1947603517749919
Ozdamar SM, Alev B, Yarat AYŞEN. The impact of arthrocentesis with and without hyaluronic acid injection in the prognosis and synovial fluid myeloperoxidase levels of patients with painful symptomatic internal derangement of temporomandibular joint: a randomised controlled clinical trial. J Oral Rehabil 2017; 44(2): 73-80. https://doi.org/10.1111/joor.12467
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.