Impact of sildenafil-containing ointment on wound healing in healthy and experimental diabetic rats.


Journal

Acta diabetologica
ISSN: 1432-5233
Titre abrégé: Acta Diabetol
Pays: Germany
ID NLM: 9200299

Informations de publication

Date de publication:
Nov 2020
Historique:
received: 30 04 2020
accepted: 17 06 2020
pubmed: 1 7 2020
medline: 15 12 2020
entrez: 1 7 2020
Statut: ppublish

Résumé

The study evaluated the effect of different concentrations of sildenafil-containing ointment on wound healing in healthy and streptozotocin (STZ)-induced diabetic rats. A total of 108 Sprague Dawley male rats aged 5 months were randomly divided into two groups: healthy and diabetes-inducing rats. Following induction of diabetes by intraperitoneal STZ injection (55 mg/kg), diabetic and healthy rats were subdivided into six groups (9 rats each). Linear incisions of the dorsal backs of rats were made. Then, rats were treated twice daily with either 2%, 2% + Fucidin, 5% sildenafil-containing ointments, oral sildenafil (13.0 mg/kg), moist exposed burn ointment or vehicle. During treatment, the percent reduction of the wound area and tensile strength were measured on days 3, 7 and 10. Furthermore, histopathology was performed on the wounded skin on similar days for the assessment of collagen synthesis and proliferation of new capillary vessels. In healthy and STZ-induced diabetic rats, the percent reduction in wound area on day 3 was significantly higher in sildenafil-containing ointment-treated groups than all other groups, whereas on day 7 only the 5% sildenafil-containing ointment-treated group showed better response in healthy rats. Although the sildenafil-containing ointment significantly showed better tensile strength than all other groups, the 5% sildenafil-treated group significantly enhanced the tensile better than the 2% and 2% + Fucidin dose. Furthermore, the histological evaluation revealed that sildenafil-containing ointment promoted collagen synthesis and proliferation of new capillary vessels. Our results suggest that sildenafil-containing ointment can provide an advantage in wound healing by promoting wound contractions and resistance to wound breakage in healthy and diabetic conditions. Therefore, 5% sildenafil-containing ointment can be used as a support factor for wound healing in healthy and diabetic conditions; however, clinical trials are required to confirm the benefits of sildenafil in wound healing.

Identifiants

pubmed: 32601730
doi: 10.1007/s00592-020-01562-0
pii: 10.1007/s00592-020-01562-0
doi:

Substances chimiques

Ointments 0
Sildenafil Citrate BW9B0ZE037

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1351-1358

Subventions

Organisme : Deanship of Academic Research at the University of Petra
ID : 15-4/2018

Références

Hamed S, Ullmann Y, Masoud M, Hellou E, Khamaysi Z, Teot L (2010) Topical erythropoietin promotes wound repair in diabetic rats. J Invest Dermatol 130:287–294
doi: 10.1038/jid.2009.219
Toker S, Gulcan E, Cayc MK, Olgun EG, Erbilen E, Ozay Y (2009) Topical atorvastatin in the treatment of diabetic wounds. Am J Med Sci 338:201–204
doi: 10.1097/MAJ.0b013e3181aaf209
Meireles GC, Santos JN, Chagas PO, Moura AP, Pinheiro AL (2008) Effectiveness of laser photobiomodulation at 660 or 780 nanometers on the repair of third-degree burns in diabetic rats. Photomed Laser Surg 26:47–54
doi: 10.1089/pho.2007.2051
Fahey TJ, Sadaty A, Jones WG, Barber A, Smoller B, Shires GT (1991) Diabetes impairs the late inflammatory response to wound healing. J Surg Res 50:308–313
doi: 10.1016/0022-4804(91)90196-S
Qunaibi EA, Disi AM, Taha MO (2009) Phenytoin enhances collagenization in excision wounds and tensile strength in incision wounds. Pharmazie 64:584–586
pubmed: 19827299
Singer A, Clark R (1999) Cutaneous wound healing. N Engl J Med 341:738–746
doi: 10.1056/NEJM199909023411006
Martin P (1997) Wound healing-aiming for perfect skin regeneration. Science 276:75–81
doi: 10.1126/science.276.5309.75
Efron DT, Most D, Barbul A (2000) Role of nitric oxide in wound healing. Curr Opin Clin Nutr Metab Care 3:197–204
doi: 10.1097/00075197-200005000-00006
Ziche M, Morbidelli L, Masini E, Amerini S, Grance HJ, Maggi CA (1994) Nitric-oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Invest 94:2036–2044
doi: 10.1172/JCI117557
Kamer E, Unalp HR, Tarcan E, Diniz G, Atahan K, Ortac R (2008) Effect of hyaluronic acid-carboxymethylcellulose adhesion barrier on wound healing: an experimental study. Wounds 20:265–272
pubmed: 25941773
Diegelmann RF, Evans MC (2004) Wound healing: an overview of acute, fibrotic and delayed healing. Front Biosci 9:283–289
doi: 10.2741/1184
Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9:653–660
doi: 10.1038/nm0603-653
El-Wakeel LM, Fouad FA, Saleem MD, Saber-Khalaf M (2019) Efficacy and tolerability of sildenafil/l -arginine combination relative to sildenafil alone in patients with organic erectile dysfunction. Andrology. https://doi.org/10.1111/andr.12671
doi: 10.1111/andr.12671 pubmed: 31267684
Serin M, Altinel D, Leblebici C et al (2018) Preoperative subcutaneous sildenafl injection increases random flap survival in rats. Acta Cir Bras 33:216–222
doi: 10.1590/s0102-865020180030000003
Simsek T, Ersoy ÖF, Özsoy Z et al (2018) Efect of sildenafl citrate on the liver structure and function in obstructive jaundice: an experimental study. Turk J Surg 34:111–116. https://doi.org/10.5152/turkjsurg.2018.3771
doi: 10.5152/turkjsurg.2018.3771 pubmed: 30023974 pmcid: 6048637
Kulshrestha S, Chawla R, Alam T, Adhikari JS, Basu M (2019) Efficacy and dermal toxicity analysis of sildenafil citrate based topical hydrogel formulation against traumatic wounds. Biomed Pharmacother 112:108571. https://doi.org/10.1016/j.biopha.2019.01.032
doi: 10.1016/j.biopha.2019.01.032 pubmed: 30798130
Tas A, Atasoy N, Ozbek H et al (2003) The effects of sildenafil citrate (Viagra) in the early phase of healing process in open wounds in dogs. Acta Vet Brno 72:273–277
doi: 10.2754/avb200372020273
National Research Council (US), Institute of Laboratory Animal Resources (US) (1985) Committee on the Care and Use of Laboratory Animals, United States. Department of Health and Human Services, National Institutes of Health (US) Guide for the Care and Use of Laboratory Animals: NIH Publication No. 86-23, revised. Bethesda, Maryland, p. 83
Al-Matubsi HY, Salim MD, El-Sharaky AS et al (2010) Activities of cyclooxygenases, and levels of prostaglandins E2 And F2 alpha, in fetopathy associated with experimental diabetic gestation. Diabetes Metab 36:43–50. https://doi.org/10.1016/j.diabet.2009.06.009
doi: 10.1016/j.diabet.2009.06.009 pubmed: 20045370
Sabale V, Kunjwani H, Sabale P (2011) Formulation and in vitro evaluation of the topical antiageing preparation of the fruit of Benincasa hispida. J Ayurveda Integr Med 2:124–128. https://doi.org/10.4103/0975-9476.85550
doi: 10.4103/0975-9476.85550 pubmed: 22022154 pmcid: 3193683
Ajwee DM, Disi AM, Qunaibi EA, Taha MO (2012) Ethosuximide and phenobarbital promote wound healing via enhancing collagenization. Chem Biol Drug Des 79:137–142. https://doi.org/10.1111/j.1747-0285.2011.01105.x
doi: 10.1111/j.1747-0285.2011.01105.x pubmed: 21332949
Vaisberg AJ, Milla M, Planas MC et al (1989) Taspine is the cicatrizant principle in Sangre de Grado extracted from Croton lechleri. Planta Med 55:140–143
doi: 10.1055/s-2006-961907
Khan AW, Kotta S, Ansari SH, Sharma RK, Amit Kumar A, Ali J (2013) Formulation development, optimization and evaluation of aloevera gel for wound healing. Pharmacogn Mag 9:S6–S10. https://doi.org/10.4103/0973-1296.117849
doi: 10.4103/0973-1296.117849 pubmed: 24143047 pmcid: 3798142
Jamshidzadeh A, Azarpira N (2011) The effects of topical sildenafil on wound healing in rat. Iran. J. Pharm. Sci. 7:43–48
Hassan SW, Abubakar MG, Umar RA, Yakubu AS, Maishanu HM, Ayeni G (2011) Pharmacological and toxicological properties of leaf extracts of Kingelia africana (Bignoniaceae). Pharmacol Toxicol 6:124–132
doi: 10.3923/jpt.2011.124.132
Li J, Chen J, Kirsner R (2007) Pathophysiology of acute wound healing. Clin Dermatol 25:9–18
doi: 10.1016/j.clindermatol.2006.09.007
Udupa AL, Kulkarni DR, Udupa SL (1995) Effect of Tridax procumbens extracts on wound healing. IJP 33:37–40
Cooper D, Yu E, Hennessey P, Ko F, Robson M (1994) Determination of endogenous cytokines in chronic wounds. Ann Surg 219:688–691
doi: 10.1097/00000658-199406000-00012
Szpaderska AM, DiPietro LA (2005) Inflammation in surgical wound healing: friend or foe? Surgery 2005(137):571–573
doi: 10.1016/j.surg.2005.01.006
Pan LR, Tang Q, Fu Q, Hu BR, Xiang JZ, Qian JQ (2005) Roles of nitric oxide in protective effect of berberine in ethanolinduced gastric ulcer mice. Acta Pharmacol Sin 26:1334–1338
doi: 10.1111/j.1745-7254.2005.00186.x
Munoz-Torres M, Jodar E, Escobar-Jimenez F, Lopez-Ibarra PJ, Luna JD (1996) Bone mineral density measured by dual X-ray absorptiometry in Spanish patients with insulin-dependent diabetes mellitus. Calcif Tissue Int 58:316–319
doi: 10.1007/BF02509378
Loder RT (1988) The influence of diabetes mellitus on the healing of closed fractures. Clin Orthop Relat Res 232:210–216
Tas A, Karasu A, Comba B, Aksu DS, Duz E, Tanritanir P (2011) Effects of sildenafil citrate on the hematological parameters in the early phase of wound healing in diabetic rats. Asian J Anim Vet Adv 6:290–296
doi: 10.3923/ajava.2011.290.296
Calnan J, Fry HJF (1962) Wound healing in rats with the antibiotic fucidic acid. Br J Pharmacol Chemother 19:321–323
doi: 10.1111/j.1476-5381.1962.tb01195.x
Perk H, Armagan A, Nazıroğlu M et al (2008) Sildenafil citrate as a phosphodiesterase inhibitor has an antioxidant effect in the blood of men. J Clin Pharm Ther 33:635–640. https://doi.org/10.1111/j.1365-2710.2008.00962.x
doi: 10.1111/j.1365-2710.2008.00962.x pubmed: 19138241
Irkorucu O, Tascilar O, Cakmak GK et al (2008) The effect of sildenafil on an animal model for ischemic colitis. Dig Dis Sci 53:1618–1623
doi: 10.1007/s10620-007-0033-9
Irkorucu O, Ucan BH, Cakmak GK et al (2009) Does sildenafil reverse the adverse effects of ischemia on ischemic colon anastomosis: yes, ‘no’. Int J Surg 7:39–43. https://doi.org/10.1016/j.ijsu.2008.10.003
doi: 10.1016/j.ijsu.2008.10.003 pubmed: 19022713
Derici H, Kamer E, Unalp HR et al (2010) Effect of sildenafil on wound healing: an experimental study. Langenbecks Arch Surg 395:713–718
doi: 10.1007/s00423-009-0471-2
Cakmak E, Karasoy Yesilada A, Sevim KZ, Sumer O, Tatlidede HS, Sakiz D (2014) Effect of sildenafil citrate on secondary healing in full thickness skin defects in experiment. Bratisl Lek Listy 115:267–271
pubmed: 25174056

Auteurs

Wael Abu Dayyih (W)

Department of Pharmaceutical Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan.

Walid Abu Rayyan (W)

Department of Pharmacology and Medical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan.

Hisham Y Al-Matubsi (HY)

Department of Pharmacology and Medical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan. almatubsi@yahoo.com.

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