Comparison of Effects of Administration of Oral or Topical Boron on Wound Healing and Oxidative Stress in Rats

Abstract

The purpose of this study was to determine the effects of boron on wound healing and further evaluate some antioxidant and oxidant characteristics. A total of 32 adult male Wistar rats were divided into four groups; control group, local boron (LB) group, oral boron (OB) group, and oral+local boron (OLB) group. Under general anesthesia, a circular full-thickness skin defect with a diameter of 1.5 cm was created on the dorsal region of the rats. Boron (10 mg/kg) was administered per oral in OB group and 3% boric acid was administered topically in LB group, and 10 mg/kg boron was administered per oral and 3% boric acid was applied topically in OLB group. Control group did not receive any medication. In histopathological examination, re-epithelialization, granulation tissue formation, collagen formation, inflammatory cell formation, and neovascularization were found to be more superior in LB and OLB groups as compared to the control and OB groups. Blood and wound tissue MDA levels in OB and OLB groups were lower with respect to the control and LB groups (p<0.05). In conclusion, oral administration of boron in addition to topical treatment contributes the wound healing due to the antioxidant property of boron in wound healing process.

Keywords

• Antioxidant,boron,malondialdehyde,rat,wound healing

Ratlarda Oral veya Topikal Olarak Uygulanan Borun Yara İyileşmesi ve Oksidatif Stres Üzerine Etkilerinin Karşılaştırılması

Abstract

Bu çalışmanın amacı, borun yara iyileşmesi ve bazı antioksidan ve oksidan parametreler üzerine olan etkisinin belirlenmesidir. Çalışmada,  toplam 32 adet erişkin erkek Wistar ratı, kontrol grubu, lokal bor (LB) grubu, oral bor (OB) grubu ve oral+lokal bor (OLB) grubu olmak üzere  ratgele dört gruba ayrıldı.  Genel anestezi altında,  ratların sırt bölgesinde 1,5 cm çapında dairesel tam kat bir deri defekti oluşturuldu. OB grubunda bulunan ratlara oral olarak 10 mg/kg bor, LB grubunda bulunan ratlara topikal % 3’lük borik asit,  OLB grubunda bulunan ratlara oral 10 mg/kg bor ile birlikte topikal olarak % 3’lük borik asit uygulandı. Kontrol grubuna ise herhangi bir ilaç uygulanmadı. Histopatalojik inceleme için yara dokusu örnekleri alındı.  Histopatolojik olarak; repitelizasyon, granulasyon dokusu oluşumu, kollagen formasyonu, yangısal hücre oluşumu ve neovaskülarizasyonun LB ve OLB gruplarında kontrol ve OB grubuna göre daha iyi olduğu belirlendi. OB ve OLB gruplarında kan ve yara dokusu MDA düzeylerinin kontrol ve LB grubuna göre düşük olduğu belirlendi (p<0,05). Sonuç olarak; yara sağaltımında, lokal olarak borik asit kullanıma ek olarak antioksidan özelliklerinden dolayı oral bor kullanımının yara iyileşmesine katkı sağladığı söylenebilir

Keywords

• Antioksidan,bor,malondialdehit,rat,yara iyileşmesi

References

1. Aebi HE. Catalase in vitro. In: Bergmeyer HU, editor. Methods of enzymatic enalysis. New York: Academic Press, 1983; pp 673-677.
2. Beckert S, Königsrainer A, Coerper S. The physiology of wound healing. Therapeutische Umschau. Revue therapeutique, 2007; 64(9): 467-472.
3. Benderdour M, Hess K, Dzondo-Gadet M, Nabet P, Belleville F, Dousset B. Boron modulates extracellular matrix and TNFα synthesis in human fibroblasts. Biochem. Biophys. Res. Commun. 1998; 246(3):746-751.
4. Benderdour M, Hess K, Gadet MD, Dousset B, Nabet P, Belleville F. Effect of boric acid solution on cartilage metabolism. Biochem. Biophys. Res. Commun. 1997; 234(1):263-268.
5. Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J. Lab. Clin. Med. 1963;61(5): 882–8.
6. Blech MF, Martin C, Borrelly J, Hartemann P. Traitement des plates profondes avec perte de substance; Interet d’une solution d’acide borique 3 %. Presse Medicale 1990a; 19:1050-1052.
7. Blech MF, Martin C, Pichon M, Borrelly J, Hartemann P. Clinical and bacteriologic course of wounds as a function of various protocols of local antisepsis. Rev. Chir. Orthop. 1990b; 76(1): 55-61.
8. Bolcal C, Yildirim V, Doganci S, Sargin M, Aydin A, Eken A, Ozal E, Kuralay E, Demirkilic U, Tatar H. Protective Effects of Antioxidant Medications on Limb Ischemia Reperfusion Injury. J. Surg. Res. 2007;139(2): 274–9.

9. Coban FK, Ince S, Kucukkurt I, Demirel HH, Hazman O. Boron attenuates malathion-induced oxidative stress and acetylcholinesterase inhibition in rats. Drug Chem. Toxicol. 2015;38(4): 391–9.
10. Deǧim Z, Çelebi N, Sayan H, Babül A, Erdoǧan D, Take G. An investigation on skin wound healing in mice with a taurine-chitosan gel formulation. Amino Acids. 2002; 22:187-198.
11. Demirci S, Doğan A, Aydın S, Dülger EÇ, Şahin F. Boron promotes streptozotocin-induced diabetic wound healing: roles in cell proliferation and migration, growth factor expression, and inflammation. Mol. Cell. Biochem. 2016; 417(1-2):119-133.
12. Demirci S, Doğan A, Karakuş E, Halıcı Z, Topçu A, Demirci E, Sahin F. Boron and Poloxamer (F68 and F127) Containing Hydrogel Formulation for Burn Wound Healing. Biol. Trace Elem. Res. 2015; 168:169-80.
13. Draper HH, Hadley M. Malondialdehyde determination as index of lipid Peroxidation. Methods Enzymol. 1990;186: 421–31.
14. Drabkin DL, Austin JH. Spectrophotometric studies. II. Preparations from washed blood cells; nitric oxide, hemoglobin and sulfhemoglobin. J Biol Chem 1935; 112(l):51.
15. Gultepe EE, Uyarlar C, Bayram İ. Supplementation of Cr Methionine During Dry Period of Dairy Cows and Its Effect on Some Production and Biochemical Parameters During Early Lactation and on Immunity of Their Offspring. Biol. Trace Elem. Res. 2018; 186(1): 143-153.
16. Luck H. Catalase. In: Bergmeyer HU (ed). Methods in analysis. London: Academy Press. 1955.
17. Ince S, Keles H, Erdogan M, Hazman O, Kucukkurt I. Protective effect of boric acid against carbon tetrachloride-induced hepatotoxicity in mice. Drug Chem Toxicol. 2012;35(3): 285–92.
18. Ince S, Kucukkurt I, Cigerci IH, Fatih Fidan A, Eryavuz A. The effects of dietary boric acid and borax supplementation on lipid peroxidation, antioxidant activity, and DNA damage in rats. J. Trace Elem. Med. Biol. 2010;24(3): 161–4.
19. Ince S, Kucukkurt I, Demirel HH, Acaroz DA, Akbel E, Cigerci IH. Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats. Chemosphere. 2014; 108, 197-204.
20. Murray F. A Comparative Review of the Pharrnacokinetics of Boric Acid in Rodents and Humans. Biol. Trace Elem. Res. 1998; 66:331-41
21. Kapan M, Mehmet S, Erdal SAK, Öngören AU. Lokal Fenitoin ve Üre Uygulamasının Yara iyileşmesi Üzerine Olan Etkilerinin Karşılaştırılması. Yeni Tıp Dergisi, 2008; 25(4):209.
22. Keast DH, Orsted H. The basic principles of wound care. Ostomy. Wound. Manage. 1998; 44(8), 24-8.
23. Korkmaz M, Turkmen R, Demirel HH, Saritas ZK. Effect of Boron on the Repair of Osteochondral Defect and Oxidative Stress in Rats: an Experimental Study. Biol. Trace Elem. Res. 2019; 187(2), 425-433.
24. Kucukkurt I, Ince S, Demirel HH, Turkmen R, Akbel E, Celik Y. The Effects of Boron on Arsenic-Induced Lipid Peroxidation and Antioxidant Status in Male and Female Rats. J. Biochem. Mol. Toxicol. 2015;29(12): 564–71.
25. Kuru R, Yarat A. Bor ve Sağlığımıza Olan Etkilerine Güncel Bir Bakış. Clin Exp Health Sci 2017; 7:104-114.
26. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 1951;193(1): 265–75.
27. Musalmah M, Nizrana MY, Fairuz AH, NoorAini AH, Azian AL, Gapor MT, Wan Ngah WZ. Comparative effects of palm vitamin E and α-tocopherol on healing and wound tissue antioxidant enzyme levels in diabetic rats. Lipids. 2005; 40(6), 575-580.
28. Nzietchueng RM, Dousset B, Franck P, Benderdour M, Nabet P, Hess K. Mechanisms implicated in the effects of boron on wound healing. J. Trace Elem. Med. Biol. 2002; 16(4), 239-244.
29. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 1979;95(2): 351–8.
30. Özler M, Şimşek K, Topal T, Öter Ş, Korkmaz A. Pinealektomili ratlarda yara iyileşmesi. Gulhane Med. J. 2010; 52: 181-184.
31. Panchatcharam M, Miriyala S, Gayathri VS, Suguna L. Curcumin improves wound healing by modulating collagen and decreasing reactive oxygen species. Mol. Cell. Biochem. 2006; 290(1-2), 87-96.
32. Shukla A, Rasik AM, Patnaik GK. Depletion of reduced glutathione, ascorbic acid, vitamin E and antioxidant defence enzymes in a healing cutaneous wound. Free Radic. Res. 1997; 26(2), 93-101.
33. Singh S, Young A, McNaught CE. The physiology of wound healing. Surgery (Oxford), 2017; 35(9): 473-477.
34. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin. Chem. 1988; 34(3):497-500.
35. Uçkun Z. Esansiyel bir komponent: bor-borun günlük alımı ve fizyolojik etkileri. J Turkish Sci. Rev. 2013; 6: 119-23.
36. Uyar A, Akyol T, Yaman T, Keleş ÖF. Ratlarda Deneysel Olarak Oluşturulan Yara Modelinde Civanperçemi (Achillea millefolium) Bitkisinin Yara İyileşmesi ve Oksidatif Stres Üzerine Etkisinin Histopatolojik ve Biyokimyasal Olarak Araştırılması. Van Veterinary Journal, 2017; 28(3):157-163.
37. Werner S, Grose R. Regulation of Wound Healing by Growth Factors and Cytokines. Physiol. Rev. 2003;83(3): 835–70.
38. Wilson JH, Ruszler PL. Long term effects of boron on layer bone strength and production parameters. Br. Poult. Sci. 1998; 39(1), 11-15.
39. Winterbourn CC, Hawkins RE, Brian M, Carrell RW. The estimation of red cell superoxide dismutase activity. J. Lab. Clin. Med. 1975;85: 337–41.