Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β

Shireen Sameen; Tagreed Altaei

doi:doi:10.11648/j.ajcem.20140206.15

| Peer-Reviewed

Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β

Shireen Sameen, Tagreed Altaei

Published in American Journal of Clinical and Experimental Medicine (Volume 2, Issue 6)

Received: 5 November 2014 Accepted: 12 November 2014 Published: 17 November 2014

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

Induced ulcer wound repair needs re-epithelialisation to replace necrotised and/or damaged tissue and to re-establish its integrity. Transforming growth factor-β (TGF-β) affects all cell types that are involved in all stages of wound healing. The assessment of induced ulcer wound healing activity was carried out through three models: First, excision model, second, induced ulcer wound using 50 mg Aspirin, and third by using 10 mg Nicorandil wound model. The animals were divided into eight groups; and were treated with different concentrations of Zinc sulphate, compared to their controls. The efficacy of Zinc sulphate on healing process of lesion induced was assessed by; body weight change, macroscopical appearance of the induced ulcers (ulcer area and wound contraction), microscopically appearance and histopathology; as well as qualitative assessment Moreover, the effect of ulcer induction on the serum levels of TGF-β according to the procedure of the kit was assessed in all groups. Different concentrations of topical Zinc sulphate have not significantly enhanced the healing of excision wounds. Thirty milligram Zinc sulphate has not significantly enhanced the healing of lesion ulcer induced by 50 mg Aspirin or 10 mg Nicorandil. Nevertheless, the 50 mg Aspirin and 10 mg Nicorandil caused delay in healing. In all groups, a significant reduction in ulcer area was observed compared to that of the baseline. Besides, a significant elevation in wound contraction was noticed compared to that of the baseline. Qualitative assessment of the healing process of the induced ulcer confirms that Aspirin or Nicorandil delay healing. Assessment of serum TGF-β level in serum showed no statistical significant elevation in those groups treated with different concentrations of Zinc sulphate compared to their control, while TGF-β level showed non-significant reduction in the group of induced ulcer by Aspirin or Nicorandil and treatment with 30 mg Zinc sulphate, compared to their controls. In conclusion, Nicorandil cause ulceration in the same manner of Aspirin, which delay the healing process, and TGF-β appears to play a more profound role in the healing process perforations than in the healing of induced ulcers in skin.

Published in	American Journal of Clinical and Experimental Medicine (Volume 2, Issue 6)
DOI	10.11648/j.ajcem.20140206.15
Page(s)	137-150
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2014. Published by Science Publishing Group

Keywords

Transforming Growth Factor-β (TGF-β), Induced Ulcer, Aspirin, Nicorandil, Zinc Sulphate

References

[1]	Yao C, Li A, Gao W, Pallua N, Steffens G. Topical Stem and Progenitor Cell Therapy for Diabetic Foot Ulcers.Int J Burns Traum; 1(1): 1726. 2011.
[2]	El Gazaerly H, Elbardisey DM, Eltokhy HM, Teaama D. Effect of Transforming Growth Factor Beta 1 on Wound Healing in Induced Diabetic Rats. Int J Health Sci; 7 (2): 160–172. 2013.
[3]	Lev-Tov H, Li CS, Dahle S, Isseroff RR. Cellular versus acellular matrix devices intreatment of diabetic foot ulcers: study protocol for a comparative efficacy randomized controlled trial.Trials, 14: 8. 2013.
[4]	Han C, Bowen WC, Li G, Demetris AJ, Michalopoulos GK, Wu T (2010). Cytosolic Phospholipase A2α and PPAR-γ Signaling Pathway Counteracts TGF-β-mediated Inhibition of Primary and Transformed Hepatocyte Growth. Hepatology; 52(2): 644–655. 2010
[5]	Navin K, Kapur MD. Transforming Growth Factor-βGoverning the Transition From Inflammation to Fibrosis in Heart Failure With Preserved Left Ventricular Function. Circulation; 4: 5-7 doi: 10.1161/CIRCHEARTFAILURE.110.960054. 2011.
[6]	Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res; 37 (5): 1528-1542. 2009.
[7]	Ciantar M, Gibson J. Nicorandil-induced oral ulceration. Malta Med J; 20 (1): 30. 2008.
[8]	Riechert S, Antunes A, Trechot P, Barbaud A, Weber M, Schmutz JL. Major aphthous stomatitis induced by Nicorandil. Eur J Dermatol; 7: 132. 1997.
[9]	Cribier B, Marquart-Elbaz C, Lipsker D, Alt M, Grosshans E. Chronic buccal ulceration induced by nicorandil. Br J Dermatol; 138: 372–373. 1998.
[10]	Shorts RH, Scully C, Avery CM, Porter SR. Nicorandil induced severe oral ulceration. Oral Surg Oral Med Oral Pathol Oral Radiol Endod; 87: 706–707. 1999.
[11]	Marquart-Elbaz C, Lipsker D, Grosshans B, Cribier B. Prevalence and clinicopathological features of nicorandil-induced oral ulceration. Ann Dermatol; 125(3): 317. 1998.
[12]	Berger A. Science Commentary: What does zinc do? Br Med J; 325: 1062-1063. 2002.
[13]	Diegelmann RF, Evans MC. Wound healing: an overview of acute, fibrotic and delayed healing. Front Biosci; 9: 283-289. 2004.
[14]	Paddock HN, Schultz GS, Mast BA. Methods in reepithelialization. A porcine model of partial-thickness wounds. Methods Mol Med78: 17-36. 2003.
[15]	Mehdipour M, Zenouz AT, Bahramian A,Yazdani J, Pouralibaba F,and Sadr K. Comparison of the Effect of Mouthwashes with and without Zinc and Fluocinolone on the Healing Process of Erosive Oral Lichen Planus. J Dent Res; 4(1): 25–28. 2010.
[16]	Sardari K, Ehsan Kakhki G, Mohri M. Evaluation of wound contraction and epithelialization after subcutaneous administration of Theranekron® in cows. Comp Clin Pathol; 16:197–200. 2007.
[17]	Gal P, Kilik R, Mokry M ,Vidinsky B, Vasilenko T, Mozes S, et al. Simple method of open skin wound healing model in corticosteroid-treated and diabetic rats: standardization of semi-quantitative and quantitative histological assessments. Vet Med; 53 (12): 652–659. 2008.
[18]	Shen Y. Plasminogen: A novel inflammatory regulator that promotes wound healing. ISBN: 978-91-7459-652-6. 2013.
[19]	Adam J. Singer, MD, Richard AF, Clark MD. Cutaneous wound healing. NJEM; 341 Number 10: 738- 746. 1999.
[20]	Agren MS, Chvapil M, Franze´n L. Enhancement of re-epithelialization with topical zinc oxide in porcine partial-thickness wounds. J Surg Res; 50: 101–5. 1991.
[21]	Bhatti I, Cohen SN, BleikerT, Lund J,Tierney G. Nicorandil-induced foreskin ulceration. Case Rep; 11: 424–425. 2009.
[22]	Guo S, DiPietro. Factors Affecting Wound Healing. J Dent Res, 89(3): 219–229. 2010.
[23]	Malde S, Wilson A. Rectal ulceration caused by the anti-anginal nicorandil: Case report of a preventable complication.Patient Saf Surg, 4: 10. 2010.
[24]	McDaid J, Reichl C,Hamzah I,Fitter S, Harbach L, SavageAP. Diverticular fistulation is associated with nicorandil usage.Ann R Coll Surg Engl; 92 (6): 463–465. 2010.
[25]	Yap T, PhilippouP, PerryM, LamW, Corbishley C,Watkin N. Nicorandil-induced penile ulcerations: a case series. BJUI; 107(2): 268–271. 2011.
[26]	Bankey P, Fiegel V, Singh R, Knighton D Cerra F. Hypoxia and endotoxin induce macrophage-mediated suppression of fibroblast proliferation. J Trauma; 29(7): 972-9. 1989.
[27]	Guo S, DiPietro. Factors Affecting Wound Healing. J Dent Res, 89(3): 219–229. 2010.
[28]	Cotran RS, Kumar V, Robbins SL, Schoen FJ. eds Robbins Pathologic Basis of Disease. Philadelphia, PA: WB Saunders; PP. 35-92. 1994.
[29]	Eming SA, Werner S, Bugnon P, Wickenhauser C, Siewe L, Utermöhlen O, et al. Accelerated wound closure in mice deficient forinterleukin-10. Am J Pathol; 170 (1): 188-202. 2007.
[30]	Gutiérrez-Fernández A, Inada M, Balbín M, Fueyo A, Pitiot AS, Astudillo A, et al. Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8). FASEB J; 21(10): 2580-91. 2007.
[31]	Joshua S. Boateng,Kerr H. Matthews,Howard N.E. Stevens,Gillian M. Eccleston. Wound Healing Dressings and Drug Delivery Systems: A Review. Wiley InterScience. Journal of pharmaceutical sciences, VOL. 97, NO. 8, 2008. DOI 10.1002/jps.21210.
[32]	Altaei T. Topical lavender oil for the treatment of recurrent aphthous ulceration. Am J Dent; 25: 39-43. 2012.
[33]	Davidson J M. Animal models for wound repair. Arch Dermatol Res; 290 (Suppl): S1–S11. 1998.
[34]	Wang XJ, Han G, Owens P, Siddiqui Y, Li AG. Role of TGF betamediated inflammation in cutaneous wound healing. J Investig Dermatol Symp Proc; 11: 112–117. 2006.
[35]	Werner S, Krieg T, Smola H. Keratinocyte-fibroblast interactions in wound healing. J Investig Dermatol; 127(5): 998–1008. 2007.
[36]	Steinbrech DS, Longaker MT, Mehrara BJ, Saadeh PB, Chin GS, Gerrets RP, et al. Fibroblast response to hypoxia: The relationship between angiogenesis and matrix regulation. J Surg Res; 84: 127. 1999.
[37]	Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G (1993). Transforming growth factor-β1 induces αsmooth muscle actin expression in granulation tissue myofibroblasts and inquiescent and growing cultured fibroblasts. J Cell Biol; 122 (1): 103–111.
[38]	EstaiMA, SuhaimiF, DasS, ShuidAN, Mohamed Z, SoelaimanI-N. Expression of TGF-β1 in the blood during fracture repair in an estrogen-deficient rat model. Clinics; 66 (12): 1807-5932. 2011.

Cite This Article

Plain Text BibTeX RIS

APA Style

Shireen Sameen, Tagreed Altaei. (2014). Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β. American Journal of Clinical and Experimental Medicine, 2(6), 137-150. https://doi.org/10.11648/j.ajcem.20140206.15

Copy | Download

ACS Style

Shireen Sameen; Tagreed Altaei. Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β. Am. J. Clin. Exp. Med. 2014, 2(6), 137-150. doi: 10.11648/j.ajcem.20140206.15

Copy | Download

AMA Style

Shireen Sameen, Tagreed Altaei. Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β. Am J Clin Exp Med. 2014;2(6):137-150. doi: 10.11648/j.ajcem.20140206.15

Copy | Download

@article{10.11648/j.ajcem.20140206.15,
  author = {Shireen Sameen and Tagreed Altaei},
  title = {Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β},
  journal = {American Journal of Clinical and Experimental Medicine},
  volume = {2},
  number = {6},
  pages = {137-150},
  doi = {10.11648/j.ajcem.20140206.15},
  url = {https://doi.org/10.11648/j.ajcem.20140206.15},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20140206.15},
  abstract = {Induced ulcer wound repair needs re-epithelialisation to replace necrotised and/or damaged tissue and to re-establish its integrity. Transforming growth factor-β (TGF-β) affects all cell types that are involved in all stages of wound healing. The assessment of induced ulcer wound healing activity was carried out through three models:  First, excision model, second, induced ulcer wound using 50 mg Aspirin, and third by using 10 mg Nicorandil wound model. The animals were divided into eight groups; and were treated with different concentrations of Zinc sulphate, compared to their controls. The efficacy of Zinc sulphate on healing process of lesion induced was assessed by; body weight change, macroscopical appearance of the induced ulcers (ulcer area and wound contraction), microscopically appearance and histopathology; as well as qualitative assessment Moreover, the effect of ulcer induction on the serum levels of TGF-β according to the procedure of the kit was assessed in all groups. Different concentrations of topical Zinc sulphate have not significantly enhanced the healing of excision wounds. Thirty milligram Zinc sulphate has not significantly enhanced the healing of lesion ulcer induced by 50 mg Aspirin or 10 mg Nicorandil. Nevertheless, the 50 mg Aspirin and 10 mg Nicorandil caused delay in healing. In all groups, a significant reduction in ulcer area was observed compared to that of the baseline. Besides, a significant elevation in wound contraction was noticed compared to that of the baseline. Qualitative assessment of the healing process of the induced ulcer confirms that Aspirin or Nicorandil delay healing. Assessment of serum TGF-β level in serum showed no statistical significant elevation in those groups treated with different concentrations of Zinc sulphate compared to their control, while TGF-β level showed non-significant reduction in the group of induced ulcer by Aspirin or Nicorandil and treatment with 30 mg Zinc sulphate, compared to their controls. In conclusion, Nicorandil cause ulceration in the same manner of Aspirin, which delay the healing process, and TGF-β appears to play a more profound role in the healing process perforations than in the healing of induced ulcers in skin.},
 year = {2014}
}

Copy | Download

TY  - JOUR
T1  - Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β
AU  - Shireen Sameen
AU  - Tagreed Altaei
Y1  - 2014/11/17
PY  - 2014
N1  - https://doi.org/10.11648/j.ajcem.20140206.15
DO  - 10.11648/j.ajcem.20140206.15
T2  - American Journal of Clinical and Experimental Medicine
JF  - American Journal of Clinical and Experimental Medicine
JO  - American Journal of Clinical and Experimental Medicine
SP  - 137
EP  - 150
PB  - Science Publishing Group
SN  - 2330-8133
UR  - https://doi.org/10.11648/j.ajcem.20140206.15
AB  - Induced ulcer wound repair needs re-epithelialisation to replace necrotised and/or damaged tissue and to re-establish its integrity. Transforming growth factor-β (TGF-β) affects all cell types that are involved in all stages of wound healing. The assessment of induced ulcer wound healing activity was carried out through three models:  First, excision model, second, induced ulcer wound using 50 mg Aspirin, and third by using 10 mg Nicorandil wound model. The animals were divided into eight groups; and were treated with different concentrations of Zinc sulphate, compared to their controls. The efficacy of Zinc sulphate on healing process of lesion induced was assessed by; body weight change, macroscopical appearance of the induced ulcers (ulcer area and wound contraction), microscopically appearance and histopathology; as well as qualitative assessment Moreover, the effect of ulcer induction on the serum levels of TGF-β according to the procedure of the kit was assessed in all groups. Different concentrations of topical Zinc sulphate have not significantly enhanced the healing of excision wounds. Thirty milligram Zinc sulphate has not significantly enhanced the healing of lesion ulcer induced by 50 mg Aspirin or 10 mg Nicorandil. Nevertheless, the 50 mg Aspirin and 10 mg Nicorandil caused delay in healing. In all groups, a significant reduction in ulcer area was observed compared to that of the baseline. Besides, a significant elevation in wound contraction was noticed compared to that of the baseline. Qualitative assessment of the healing process of the induced ulcer confirms that Aspirin or Nicorandil delay healing. Assessment of serum TGF-β level in serum showed no statistical significant elevation in those groups treated with different concentrations of Zinc sulphate compared to their control, while TGF-β level showed non-significant reduction in the group of induced ulcer by Aspirin or Nicorandil and treatment with 30 mg Zinc sulphate, compared to their controls. In conclusion, Nicorandil cause ulceration in the same manner of Aspirin, which delay the healing process, and TGF-β appears to play a more profound role in the healing process perforations than in the healing of induced ulcers in skin.
VL  - 2
IS  - 6
ER  -

Copy | Download

Author Information

Shireen Sameen

College of Pharmacy/ Hawler Medical University, Erbil, Kurdistan-Iraq
Tagreed Altaei

College of Dentistry/ Hawler Medical University, Erbil, Kurdistan-Iraq

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Shireen Sameen, Tagreed Altaei. (2014). Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β. American Journal of Clinical and Experimental Medicine, 2(6), 137-150. https://doi.org/10.11648/j.ajcem.20140206.15

Copy | Download

ACS Style

Shireen Sameen; Tagreed Altaei. Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β. Am. J. Clin. Exp. Med. 2014, 2(6), 137-150. doi: 10.11648/j.ajcem.20140206.15

Copy | Download

AMA Style

Shireen Sameen, Tagreed Altaei. Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β. Am J Clin Exp Med. 2014;2(6):137-150. doi: 10.11648/j.ajcem.20140206.15

Copy | Download

@article{10.11648/j.ajcem.20140206.15,
  author = {Shireen Sameen and Tagreed Altaei},
  title = {Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β},
  journal = {American Journal of Clinical and Experimental Medicine},
  volume = {2},
  number = {6},
  pages = {137-150},
  doi = {10.11648/j.ajcem.20140206.15},
  url = {https://doi.org/10.11648/j.ajcem.20140206.15},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20140206.15},
  abstract = {Induced ulcer wound repair needs re-epithelialisation to replace necrotised and/or damaged tissue and to re-establish its integrity. Transforming growth factor-β (TGF-β) affects all cell types that are involved in all stages of wound healing. The assessment of induced ulcer wound healing activity was carried out through three models:  First, excision model, second, induced ulcer wound using 50 mg Aspirin, and third by using 10 mg Nicorandil wound model. The animals were divided into eight groups; and were treated with different concentrations of Zinc sulphate, compared to their controls. The efficacy of Zinc sulphate on healing process of lesion induced was assessed by; body weight change, macroscopical appearance of the induced ulcers (ulcer area and wound contraction), microscopically appearance and histopathology; as well as qualitative assessment Moreover, the effect of ulcer induction on the serum levels of TGF-β according to the procedure of the kit was assessed in all groups. Different concentrations of topical Zinc sulphate have not significantly enhanced the healing of excision wounds. Thirty milligram Zinc sulphate has not significantly enhanced the healing of lesion ulcer induced by 50 mg Aspirin or 10 mg Nicorandil. Nevertheless, the 50 mg Aspirin and 10 mg Nicorandil caused delay in healing. In all groups, a significant reduction in ulcer area was observed compared to that of the baseline. Besides, a significant elevation in wound contraction was noticed compared to that of the baseline. Qualitative assessment of the healing process of the induced ulcer confirms that Aspirin or Nicorandil delay healing. Assessment of serum TGF-β level in serum showed no statistical significant elevation in those groups treated with different concentrations of Zinc sulphate compared to their control, while TGF-β level showed non-significant reduction in the group of induced ulcer by Aspirin or Nicorandil and treatment with 30 mg Zinc sulphate, compared to their controls. In conclusion, Nicorandil cause ulceration in the same manner of Aspirin, which delay the healing process, and TGF-β appears to play a more profound role in the healing process perforations than in the healing of induced ulcers in skin.},
 year = {2014}
}

Copy | Download

TY  - JOUR
T1  - Efficacy of Topical Zinc Sulphate on Wound Healing of Experimentally Induced Skin Ulcers by Nicorandil and Induction Effect on Transforming Growth Factor-β
AU  - Shireen Sameen
AU  - Tagreed Altaei
Y1  - 2014/11/17
PY  - 2014
N1  - https://doi.org/10.11648/j.ajcem.20140206.15
DO  - 10.11648/j.ajcem.20140206.15
T2  - American Journal of Clinical and Experimental Medicine
JF  - American Journal of Clinical and Experimental Medicine
JO  - American Journal of Clinical and Experimental Medicine
SP  - 137
EP  - 150
PB  - Science Publishing Group
SN  - 2330-8133
UR  - https://doi.org/10.11648/j.ajcem.20140206.15
AB  - Induced ulcer wound repair needs re-epithelialisation to replace necrotised and/or damaged tissue and to re-establish its integrity. Transforming growth factor-β (TGF-β) affects all cell types that are involved in all stages of wound healing. The assessment of induced ulcer wound healing activity was carried out through three models:  First, excision model, second, induced ulcer wound using 50 mg Aspirin, and third by using 10 mg Nicorandil wound model. The animals were divided into eight groups; and were treated with different concentrations of Zinc sulphate, compared to their controls. The efficacy of Zinc sulphate on healing process of lesion induced was assessed by; body weight change, macroscopical appearance of the induced ulcers (ulcer area and wound contraction), microscopically appearance and histopathology; as well as qualitative assessment Moreover, the effect of ulcer induction on the serum levels of TGF-β according to the procedure of the kit was assessed in all groups. Different concentrations of topical Zinc sulphate have not significantly enhanced the healing of excision wounds. Thirty milligram Zinc sulphate has not significantly enhanced the healing of lesion ulcer induced by 50 mg Aspirin or 10 mg Nicorandil. Nevertheless, the 50 mg Aspirin and 10 mg Nicorandil caused delay in healing. In all groups, a significant reduction in ulcer area was observed compared to that of the baseline. Besides, a significant elevation in wound contraction was noticed compared to that of the baseline. Qualitative assessment of the healing process of the induced ulcer confirms that Aspirin or Nicorandil delay healing. Assessment of serum TGF-β level in serum showed no statistical significant elevation in those groups treated with different concentrations of Zinc sulphate compared to their control, while TGF-β level showed non-significant reduction in the group of induced ulcer by Aspirin or Nicorandil and treatment with 30 mg Zinc sulphate, compared to their controls. In conclusion, Nicorandil cause ulceration in the same manner of Aspirin, which delay the healing process, and TGF-β appears to play a more profound role in the healing process perforations than in the healing of induced ulcers in skin.
VL  - 2
IS  - 6
ER  -

Copy | Download