Research Article
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Lokal Hümik Uygulamasının Yara İyileşmesi Üzerine Etkisinin Değerlendirilmesi

Year 2021, Volume: 24 Issue: 4, 326 - 336, 03.01.2022
https://doi.org/10.7126/cumudj.869690

Abstract

Amaç:
Bu çalışmanın amacı; hümik asitin topikal olarak uygulanmasının ratlarda ağız mukozasındaki yara iyileşmesine etkilerinin, histopatolojik ve histomorfometrik olarak araştırılmasıdır.
Gereç ve Yöntemler
Denek olarak 12 haftalık, ortalama ağırlıkları 280-300 gr olan Wistar cinsi 72 adet erkek rat kullanıldı. Ratlar rastgele seçilerek hiç bir ajan uygulanmayan kontrol grubu (K), klorheksidin (%0.12) grubu (CHX), 80 mg/kg hümik asit grubu (HA80) ve 150 mg/kg hümik asit grubu (HA150) olmak üzere 4 ana gruba ayrıldı. Ratlarda palatinal bölgede, punch ile 5 mm çapında mukozal defekt oluşturuldu. Bu gruplar kendi içerisinde 7., 14. ve 21. günlerde sakrifiye edilmek üzere 3 alt gruba ayrıldı. Ratlar sakrifiye edildikten sonra histopatolojik inceleme için doku örnekleri alındı. Histopatolojik değerlendirmede; epitelizasyon, ülserasyon, polimorfo nükleer lökositler (PNL), mononükleer hücreler (MNL), fibroblast ve vaskülarizasyona bakıldı. Ayrıca doku örnekleri histomorfometrik inceleme için fotoğraflanarak bilgisayar ortamına aktarıldı.
Bulgular
Yapılan istatistiksel analiz sonucunda tüm gruplar arasında 7.,14. ve 21. günlerde epitelizasyon derecesi, PNL ve MNL hücre infiltratı açısından anlamlı bir fark bulunmadı. HA150 grubundaki ülsere alanlar diğer gruplara oranla daha az miktardaydı ve bu fark istatistiksel olarak anlamlıydı (p<0,05). Vaskülarizasyon değerlerine bakıldığında 7. günde K grubu ve HA150 grubu daha iyi sonuçlar gösterdi (p<0,05). 14. ve 21. günlerde ise gruplar arasında anlamlı bir fark bulunmadı (p>0,05). Yara yüzey alan ölçümleri, HA150 grubunda diğer gruplara kıyasla daha düşük miktardaydı ve bu sonuç, HA150 grubundaki iyileşmenin daha iyi olduğunu gösterdi (p<0,05).
Sonuç
Bu çalışmanın sonucunda hümik asitin, ağız boşluğundaki yara iyileşmesini arttırdığı görüldü. Ayrıca klorheksidinin yara iyileşmesini olumsuz yönde etkilemediği tespit edildi.

Supporting Institution

Cumhuriyet Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Project Number

diş 216

Thanks

Prof. Dr. Ahmet Tutar (Sakarya Üniversitesi Fen Edebiyat Fakültesi Kimya Bölümü) Dr. Öğr. Üy. Zinet Çınar (Cumhuriyet Üniversitesi Temel Tıp Bilimleri Biyoistatistik)

References

  • Hunt, T.K., Basic principles of wound healing. Journal of Trauma and Acute Care Surgery, 1990. 30: p. 122-128.
  • Pereira, R.F. and P.J. Bartolo, Traditional therapies for skin wound healing. Advances in wound care, 2016. 5(5): p. 208-229.
  • Han, G. and R. Ceilley, Chronic wound healing: a review of current management and treatments. Advances in therapy, 2017. 34(3): p. 599-610.
  • Krausz, A.E., et al., Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent. Nanomedicine: Nanotechnology, Biology and Medicine, 2015. 11(1): p. 195-206.
  • Low, S.B. and S.G. Ciancio, Reviewing nonsurgical periodontal therapy. The Journal of the American Dental Association, 1990. 121(4): p. 467-470.
  • Marti, S., et al., Use of topical healing agents on scrotal wounds after surgical castration in weaned beef calves. The Canadian Veterinary Journal, 2017. 58(10): p. 1081.
  • Oryan, A., E. Alemzadeh, and A. Moshiri, Biological properties and therapeutic activities of honey in wound healing: A narrative review and meta-analysis. Journal of tissue viability, 2016. 25(2): p. 98-118.
  • Lev-Tov, H., Topical valsartan increases the healing pressure on wounds. Science Translational Medicine, 2017. 9(415): p. eaaq1231.
  • Schepetkin, I., A. Khlebnikov, and B.S. Kwon, Medical drugs from humus matter: focus on mumie. Drug development research, 2002. 57(3): p. 140-159.
  • Islam, K.M.S., A. Schuhmacher, and J. Gropp, Humic acid substances in animal agriculture. Pakistan Journal of nutrition, 2005. 4(3): p. 126-134.
  • Bernacchi, F., et al., In vivo cytogenetic effects of natural humic acid. Mutagenesis, 1996. 11(5): p. 467-469.
  • Santos, A.d., et al., Interaction between humic substances and metallic ions: a selectivity study of humic substances and their possible therapeutic application. Journal of the Brazilian Chemical Society, 2007. 18(4): p. 824-830.
  • Thiel, K., et al., Comparison of the in vitro activities of ammonium humate and of enzymically oxidized chlorogenic and caffeic acids against type 1 and type 2 human herpes virus (author's transl). Die Pharmazie, 1981. 36(1): p. 50-53.
  • Lotosh, T. Experimental bases and prospects for the use of humic acid preparations from peat in medicine and agricultural production. in Nauchnye doklady vysshei shkoly. Biologicheskie nauki. 1991.
  • Laub, R., Acute systemic toxicity studies of natural product and synthetic humates. Laub BioChem Corp, August, 1998.
  • Ji, Y., et al., Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats. Acta Pharmaceutica Sinica B, 2016. 6(2): p. 132-140.
  • Çalışır, M., et al., Humic Acid Enhances Wound Healing in the Rat Palate. Evidence-Based Complementary and Alternative Medicine, 2018. 2018.
  • de Melo, B.A.G., F.L. Motta, and M.H.A. Santana, Humic acids: Structural properties and multiple functionalities for novel technological developments. Materials Science and Engineering: C, 2016. 62: p. 967-974.
  • Singer, A.J. and R.A. Clark, Cutaneous wound healing. New England journal of medicine, 1999. 341(10): p. 738-746.
  • Gau, R.-J., et al., Humic acid suppresses the LPS-induced expression of cell-surface adhesion proteins through the inhibition of NF-κB activation. Toxicology and applied pharmacology, 2000. 166(1): p. 59-67.
  • Mariano, R.C., et al., Effect of topical application of chlorhexidine and metronidazole on the tissue repair of palatal wounds of rats: a clinical and histomorphometric study. Oral surgery, oral medicine, oral pathology and oral radiology, 2015. 119(5): p. 505-513.
  • da Silveira Teixeira, D., et al., Topical chlorhexidine, povidone-iodine and erythromycin in the repair of traumatic ulcers on the rat tongue: Clinical, histological and microbiological evaluation. Archives of oral biology, 2018. 87: p. 218-225.
  • Abshenas, J., R. Kheirandish, and A.R. Salary, Gastroprotective effect of mummy on induced gastric ulcer in rats. Comparative Clinical Pathology, 2014. 23(2): p. 305-309.
  • Brzozowski, T., A. Dembiński, and S. Konturek, Influence of Tołpa Peat Preparation on gastroprotection and on gastric and duodenal ulcers. Acta poloniae pharmaceutica, 1994. 51(1): p. 103-107.
  • Khedr, R.I., et al., Detection of the Timing of Human Skin Wounds by Immunohistochemical Analysis of CD14. Arab Journal of Forensic Sciences & Forensic Medicine (AJFSFM), 2020. 1(10): p. 1357.
  • Süntar, I.P., et al., Investigations on the in vivo wound healing potential of Hypericum perforatum L. Journal of ethnopharmacology, 2010. 127(2): p. 468-477.
  • Knuuttila, M., K.U. Paunio, and H. Mielityinen, Effect of chlorhexidine gluconate on acute nonmicrobial inflammation reaction. Journal of periodontology, 1978. 49(2): p. 96-101.
  • Hoffmann, T., et al., Clinical controlled study on plaque and gingivitis reduction under long-term use of low-dose chlorhexidine solutions in a population exhibiting good oral hygiene. Clinical oral investigations, 2001. 5(2): p. 89-95.
  • Van Rensburg, C., et al., Brown coal derived humate inhibits contact hypersensitivity; an efficacy, toxicity and teratogenicity study in rats. Inflammation, 2007. 30(5): p. 148-152.
  • Çalışır, M., et al., The histopathological and morphometric investigation of the effects of systemically administered humic acid on alveolar bone loss in ligature‐induced periodontitis in rats. Journal of Periodontal Research, 2016. 51(4): p. 499-507.
  • Nagy, J.A., A.M. Dvorak, and H.F. Dvorak, VEGF-A and the induction of pathological angiogenesis. Annu. Rev. Pathol. Mech. Dis., 2007. 2: p. 251-275.
  • Vivek Shetty, C.N.B., Wound Healing. Peteron’s Principles of Oral and Maxillofacial Surgery 2nd ed, 2004: p. 3-16.
  • Goldschmidt, P., R. Cogen, and S. Taubman, Cytopathologic effects of chlorhexidine on human cells. Journal of periodontology, 1977. 48(4): p. 212-215.
  • Alleyn, C.D., et al., The effect of chlorhexidine treatment of root surfaces on the attachment of human gingival fibroblasts in vitro. Journal of periodontology, 1991. 62(7): p. 434-438.
  • Cheng, M.-L., et al., Humic Acid Induces Oxidative DNA Damage, Growth Retardation, and Apoptosis in Human Primary Fibroblasts. Experimental Biology and Medicine, 2003. 228(4): p. 413-423.
  • Krzemiński, T.F., et al., Angiogenesis and cardioprotection after TNFα-inducer-Tolpa Peat Preparation treatment in rat's hearts after experimental myocardial infarction in vivo. Vascular pharmacology, 2005. 43(3): p. 164-170.
  • Hammad, H., et al., Effects of topically applied agents on intra‐oral wound healing in a rat model: a clinical and histomorphometric study. International journal of dental hygiene, 2011. 9(1): p. 9-16

EFFECT OF TOPICAL HUMIC ACID ON EXCISIONAL PALATAL WOUND HEALING: A HISTOPATHOLOGICAL AND HISTOMORPHOMETRIC STUDY IN RATS

Year 2021, Volume: 24 Issue: 4, 326 - 336, 03.01.2022
https://doi.org/10.7126/cumudj.869690

Abstract

Background:
The purpose of the present study was to examine the effects of topical humic acid application on healing in oral mucosa wound in rats.
Material and Methods
A total of 12-week-old 72 Wistar male rats weighing 280-300 gr were used in the study. The rats were randomly grouped in 4 groups as the Control Group (K) to which no applications were made, Chlorhexidine (0.12%) Group (CHX), 80 mg/kg Humic Acid Group (HA80), and 150 mg/kg Humic Acid Group (HA150). Mucosal defects of 5-mm-diameter were induced with punch in the palatal areas of the rats. These groups were further divided into 3 sub-groups to be sacrificed on days 7, 14 and 21. Epithelization, ülceration, polymorphic nuclear leukocytes (PNL), mononuclear cells (MNL), fibroblast and vascularization were examined in histopathologic evaluations. In addition, photos of the tissue samples were taken and transferred to the computer medium for histo-morphometric examinations.
Results
As a result of the statistical analyses, no significant differences were detected among the groups in terms of epithelization degree, PNL and MNL cell infiltration on days 7, 14 and 21. The ulcerated areas were low in HA150 Group compared to the other groups, and there was a significant difference in this respect (p<0.05). Vascularization degrees were evaluated, the K Group and HA150 Group showed better results on day 7 (p<0.05). On days 14 and 21, no significant differences were detected among the groups (p>0.05). Wound area measurement scores were lower in HA150 Group compared to the other groups, and this result showed that the healing in HA150 Group was better (p<0.05).
Conclusions
As a result of the present study, it was found that humic acid increased wound healing in oral cavity.

Project Number

diş 216

References

  • Hunt, T.K., Basic principles of wound healing. Journal of Trauma and Acute Care Surgery, 1990. 30: p. 122-128.
  • Pereira, R.F. and P.J. Bartolo, Traditional therapies for skin wound healing. Advances in wound care, 2016. 5(5): p. 208-229.
  • Han, G. and R. Ceilley, Chronic wound healing: a review of current management and treatments. Advances in therapy, 2017. 34(3): p. 599-610.
  • Krausz, A.E., et al., Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent. Nanomedicine: Nanotechnology, Biology and Medicine, 2015. 11(1): p. 195-206.
  • Low, S.B. and S.G. Ciancio, Reviewing nonsurgical periodontal therapy. The Journal of the American Dental Association, 1990. 121(4): p. 467-470.
  • Marti, S., et al., Use of topical healing agents on scrotal wounds after surgical castration in weaned beef calves. The Canadian Veterinary Journal, 2017. 58(10): p. 1081.
  • Oryan, A., E. Alemzadeh, and A. Moshiri, Biological properties and therapeutic activities of honey in wound healing: A narrative review and meta-analysis. Journal of tissue viability, 2016. 25(2): p. 98-118.
  • Lev-Tov, H., Topical valsartan increases the healing pressure on wounds. Science Translational Medicine, 2017. 9(415): p. eaaq1231.
  • Schepetkin, I., A. Khlebnikov, and B.S. Kwon, Medical drugs from humus matter: focus on mumie. Drug development research, 2002. 57(3): p. 140-159.
  • Islam, K.M.S., A. Schuhmacher, and J. Gropp, Humic acid substances in animal agriculture. Pakistan Journal of nutrition, 2005. 4(3): p. 126-134.
  • Bernacchi, F., et al., In vivo cytogenetic effects of natural humic acid. Mutagenesis, 1996. 11(5): p. 467-469.
  • Santos, A.d., et al., Interaction between humic substances and metallic ions: a selectivity study of humic substances and their possible therapeutic application. Journal of the Brazilian Chemical Society, 2007. 18(4): p. 824-830.
  • Thiel, K., et al., Comparison of the in vitro activities of ammonium humate and of enzymically oxidized chlorogenic and caffeic acids against type 1 and type 2 human herpes virus (author's transl). Die Pharmazie, 1981. 36(1): p. 50-53.
  • Lotosh, T. Experimental bases and prospects for the use of humic acid preparations from peat in medicine and agricultural production. in Nauchnye doklady vysshei shkoly. Biologicheskie nauki. 1991.
  • Laub, R., Acute systemic toxicity studies of natural product and synthetic humates. Laub BioChem Corp, August, 1998.
  • Ji, Y., et al., Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats. Acta Pharmaceutica Sinica B, 2016. 6(2): p. 132-140.
  • Çalışır, M., et al., Humic Acid Enhances Wound Healing in the Rat Palate. Evidence-Based Complementary and Alternative Medicine, 2018. 2018.
  • de Melo, B.A.G., F.L. Motta, and M.H.A. Santana, Humic acids: Structural properties and multiple functionalities for novel technological developments. Materials Science and Engineering: C, 2016. 62: p. 967-974.
  • Singer, A.J. and R.A. Clark, Cutaneous wound healing. New England journal of medicine, 1999. 341(10): p. 738-746.
  • Gau, R.-J., et al., Humic acid suppresses the LPS-induced expression of cell-surface adhesion proteins through the inhibition of NF-κB activation. Toxicology and applied pharmacology, 2000. 166(1): p. 59-67.
  • Mariano, R.C., et al., Effect of topical application of chlorhexidine and metronidazole on the tissue repair of palatal wounds of rats: a clinical and histomorphometric study. Oral surgery, oral medicine, oral pathology and oral radiology, 2015. 119(5): p. 505-513.
  • da Silveira Teixeira, D., et al., Topical chlorhexidine, povidone-iodine and erythromycin in the repair of traumatic ulcers on the rat tongue: Clinical, histological and microbiological evaluation. Archives of oral biology, 2018. 87: p. 218-225.
  • Abshenas, J., R. Kheirandish, and A.R. Salary, Gastroprotective effect of mummy on induced gastric ulcer in rats. Comparative Clinical Pathology, 2014. 23(2): p. 305-309.
  • Brzozowski, T., A. Dembiński, and S. Konturek, Influence of Tołpa Peat Preparation on gastroprotection and on gastric and duodenal ulcers. Acta poloniae pharmaceutica, 1994. 51(1): p. 103-107.
  • Khedr, R.I., et al., Detection of the Timing of Human Skin Wounds by Immunohistochemical Analysis of CD14. Arab Journal of Forensic Sciences & Forensic Medicine (AJFSFM), 2020. 1(10): p. 1357.
  • Süntar, I.P., et al., Investigations on the in vivo wound healing potential of Hypericum perforatum L. Journal of ethnopharmacology, 2010. 127(2): p. 468-477.
  • Knuuttila, M., K.U. Paunio, and H. Mielityinen, Effect of chlorhexidine gluconate on acute nonmicrobial inflammation reaction. Journal of periodontology, 1978. 49(2): p. 96-101.
  • Hoffmann, T., et al., Clinical controlled study on plaque and gingivitis reduction under long-term use of low-dose chlorhexidine solutions in a population exhibiting good oral hygiene. Clinical oral investigations, 2001. 5(2): p. 89-95.
  • Van Rensburg, C., et al., Brown coal derived humate inhibits contact hypersensitivity; an efficacy, toxicity and teratogenicity study in rats. Inflammation, 2007. 30(5): p. 148-152.
  • Çalışır, M., et al., The histopathological and morphometric investigation of the effects of systemically administered humic acid on alveolar bone loss in ligature‐induced periodontitis in rats. Journal of Periodontal Research, 2016. 51(4): p. 499-507.
  • Nagy, J.A., A.M. Dvorak, and H.F. Dvorak, VEGF-A and the induction of pathological angiogenesis. Annu. Rev. Pathol. Mech. Dis., 2007. 2: p. 251-275.
  • Vivek Shetty, C.N.B., Wound Healing. Peteron’s Principles of Oral and Maxillofacial Surgery 2nd ed, 2004: p. 3-16.
  • Goldschmidt, P., R. Cogen, and S. Taubman, Cytopathologic effects of chlorhexidine on human cells. Journal of periodontology, 1977. 48(4): p. 212-215.
  • Alleyn, C.D., et al., The effect of chlorhexidine treatment of root surfaces on the attachment of human gingival fibroblasts in vitro. Journal of periodontology, 1991. 62(7): p. 434-438.
  • Cheng, M.-L., et al., Humic Acid Induces Oxidative DNA Damage, Growth Retardation, and Apoptosis in Human Primary Fibroblasts. Experimental Biology and Medicine, 2003. 228(4): p. 413-423.
  • Krzemiński, T.F., et al., Angiogenesis and cardioprotection after TNFα-inducer-Tolpa Peat Preparation treatment in rat's hearts after experimental myocardial infarction in vivo. Vascular pharmacology, 2005. 43(3): p. 164-170.
  • Hammad, H., et al., Effects of topically applied agents on intra‐oral wound healing in a rat model: a clinical and histomorphometric study. International journal of dental hygiene, 2011. 9(1): p. 9-16
There are 37 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original Research Articles
Authors

Yusuf Ziya Dönmez 0000-0002-1021-5756

Aysun Akpınar 0000-0002-6740-3598

Fahrettin Göze 0000-0002-6451-2967

Project Number diş 216
Publication Date January 3, 2022
Submission Date January 27, 2021
Published in Issue Year 2021Volume: 24 Issue: 4

Cite

EndNote Dönmez YZ, Akpınar A, Göze F (January 1, 2022) EFFECT OF TOPICAL HUMIC ACID ON EXCISIONAL PALATAL WOUND HEALING: A HISTOPATHOLOGICAL AND HISTOMORPHOMETRIC STUDY IN RATS. Cumhuriyet Dental Journal 24 4 326–336.

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