Combined effects of photobiomodulation and curcumin on mast cells and wound strength in wound healing of streptozotocin-induced diabetes in rats


We investigated the probable involvement of mast cell degranulation and their numbers in the remodeling step of wound healing in a diabetic ischemic skin wound model treated with photobiomodulation plus curcumin. A total of 108 adult male Wistar rats were randomized into one healthy control and five diabetic groups. Type I diabetes was inflicted in 90 of the 108 rats. After 1 month, an excisional wound was generated in each of the 108 rats. There were one healthy group (group 1) and five diabetic groups as follows: group 2 was the untreated diabetic control group and group 3 rats were treated with sesame oil. Rats in group 4 were treated with photobiomodulation (890 nm, 890 ± 10 nm, 80 Hz, 0.2 J/cm2) and those in group 5 received curcumin dissolved in sesame oil. Group 6 rats were treated with photobiomodulation and curcumin. We conducted stereological and tensiometric tests on days 4, 7, and 15 after treatment. The results indicated that photobiomodulation significantly improved wound strength in the diabetic rats and significantly decreased the total numbers of mast cells. The diabetic control group had significantly reduced tensiometric properties of the healing wounds and a significant increase in the total numbers of mast cells. Photobiomodulation significantly improved the healing process in diabetic animals and significantly decreased the total number of mast cells. The increased numbers of mast cells in the diabetic control group negatively affected tensiometric properties of the ischemic skin wound.

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  1. 1.

    C.f.D. Control, prevention, national diabetes statistics report (2017), Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services.

  2. 2.

    Holloway S (2019) Skin considerations for older adults with wounds. Br J Commun Nursing 24:S15–S19

    Google Scholar 

  3. 3.

    Lima AL, Illing T, Schliemann S, Elsner P (2017) Cutaneous manifestations of diabetes mellitus: a review. Am J Clin Dermatol 18:541–553

    PubMed  Google Scholar 

  4. 4.

    Kim JH, Yoon NY, Kim DH, Jung M, Jun M, Park HY, Chung CH, Lee K, Kim S, Park CS, Liu KH, Choi EH (2018) Impaired permeability and antimicrobial barriers in type 2 diabetes skin are linked to increased serum levels of advanced glycation end-product. Exp Dermatol 27:815–823

    CAS  PubMed  Google Scholar 

  5. 5.

    Alexiadou K, Doupis J (2012) Management of diabetic foot ulcers. Diabet Ther 3:4

    Google Scholar 

  6. 6.

    Lauterbach S, Kostev K, Kohlmann T (2010) Prevalence of diabetic foot syndrome and its risk factors in the UK. J Wound Care 19:333–337

    CAS  PubMed  Google Scholar 

  7. 7.

    Guo SA, DiPietro LA (2010) Factors affecting wound healing. J Dent Res 89:219–229

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Pendsey SP (2010) Understanding diabetic foot. Int J Diabet Develop Count 30:75–79

    Google Scholar 

  9. 9.

    Yang P, Pei Q, Yu T, Chang Q, Wang D, Gao M, Zhang X, Liu Y (2016) Compromised wound healing in ischemic type 2 diabetic rats. PLoS One 11:e0152068

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Wulff BC, Wilgus TA (2013) Mast cell activity in the healing wound: more than meets the eye? Exp Dermatol 22:507–510

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Ma M, Jiang T, Li N, Aliya A, Tuhan A (2015) Treatment and mechanism of BMMSCs on deep II degree scald of hamster skin. Genet Mol Res 14:8244–8251

    CAS  PubMed  Google Scholar 

  12. 12.

    Shiota N, Nishikori Y, Kakizoe E, Shimoura K, Niibayashi T, Shimbori C, Tanaka T, Okunishi H (2010) Pathophysiological role of skin mast cells in wound healing after scald injury: study with mast cell-deficient W/Wv mice. Int Arch Allergy Immunol 151:80–88

    PubMed  Google Scholar 

  13. 13.

    Weller K, Foitzik K, Paus R, Syska W, Maurer M, Weller K, Foitzik K, Paus R, Syska W, Maurer M (2006) Mast cells are required for normal healing of skin wounds in mice. FASEB J 20:2366–2368

    CAS  PubMed  Google Scholar 

  14. 14.

    Iba Y, Shibata A, Kato M, Masukawa T (2004) Possible involvement of mast cells in collagen remodeling in the late phase of cutaneous wound healing in mice. Int Immunopharmacol 4:1873–1880

    CAS  PubMed  Google Scholar 

  15. 15.

    Garbuzenko E, Nagler A, Pickholtz D, Gillery P, Reich R, Maquart FX, Levi-Schaffer F (2002) Human mast cells stimulate fibroblast proliferation, collagen synthesis and lattice contraction: a direct role for mast cells in skin fibrosis. Clin Exp Allergy 32:237–246

    CAS  PubMed  Google Scholar 

  16. 16.

    Ng MF (2010) The role of mast cells in wound healing. Int Wound J 7:55–61

    PubMed  Google Scholar 

  17. 17.

    Tellechea A, Leal EC, Kafanas A, Auster ME, Kuchibhotla S, Ostrovsky Y, Tecilazich F, Baltzis D, Zheng Y, Carvalho E (2016) Mast cells regulate wound healing in diabetes. Diabetes 65:2006–2019

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Romana-Souza B, Nascimento AP, Monte-Alto-Costa A (2009) Propranolol improves cutaneous wound healing in streptozotocin-induced diabetic rats. Eur J Pharmacol 611:77–84

    CAS  PubMed  Google Scholar 

  19. 19.

    Arul V, Kartha R, Jayakumar R (2007) A therapeutic approach for diabetic wound healing using biotinylated GHK incorporated collagen matrices. Life Sci 80:275–284

    CAS  PubMed  Google Scholar 

  20. 20.

    Dadpay M, Sharifian Z, Bayat M, Bayat M, Dabbagh A (2012) Effects of pulsed infra-red low level-laser irradiation on open skin wound healing of healthy and streptozotocin-induced diabetic rats by biomechanical evaluation. J Photochem Photobiol B Biol 111:1–8

    CAS  Google Scholar 

  21. 21.

    Sharifian Z, Bayat M, Alidoust M, Farahani RM, Bayat M, Rezaie F, Bayat H (2014) Histological and gene expression analysis of the effects of pulsed low-level laser therapy on wound healing of streptozotocin-induced diabetic rats. Lasers Med Sci 29:1227–1235

    PubMed  Google Scholar 

  22. 22.

    Fathabadie FF, Bayat M, Amini A, Bayat M, Rezaie F (2013) Effects of pulsed infra-red low level-laser irradiation on mast cells number and degranulation in open skin wound healing of healthy and streptozotocin-induced diabetic rats. J Cosmet Laser Ther 15:294–304

    PubMed  Google Scholar 

  23. 23.

    Khoshvaghti A, Zibamanzarmofrad M, Bayat M (2011) Effect of low-level treatment with an 80-Hz pulsed infrared diode laser on mast-cell numbers and degranulation in a rat model of third-degree burn. Photomed Laser Surg 29:597–604

    PubMed  Google Scholar 

  24. 24.

    Ammon HP, Wahl MA (1991) Pharmacology of Curcuma longa. Planta Med 57:1–7

    CAS  PubMed  Google Scholar 

  25. 25.

    Akbik D, Ghadiri M, Chrzanowski W, Rohanizadeh R (2014) Curcumin as a wound healing agent. Life Sci 116:1–7

    CAS  PubMed  Google Scholar 

  26. 26.

    Zhang Y, McClain SA, Lee H-M, Elburki MS, Yu H, Gu Y, Zhang Y, Wolff M, Johnson F, Golub LM (2016) A novel chemically modified curcumin “normalizes” wound-healing in rats with experimentally induced type I diabetes: initial studies, Journal of diabetes research, 2016

  27. 27.

    Sidhu GS, Mani H, Gaddipati JP, Singh AK, Seth P, Banaudha KK, Patnaik GK, Maheshwari RK (1999) Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice. Wound Repair Regen 7:362–374

    CAS  PubMed  Google Scholar 

  28. 28.

    Zhang N, Li H, Jia J, He M (2015) Anti-inflammatory effect of curcumin on mast cell-mediated allergic responses in ovalbumin-induced allergic rhinitis mouse. Cell Immunol 298:88–95

    CAS  PubMed  Google Scholar 

  29. 29.

    Choi Y-H, Yan G-H, Chai OH, Song CH (2010) Inhibitory effects of curcumin on passive cutaneous anaphylactoid response and compound 48/80-induced mast cell activation. Anatomy Cell Biol 43:36–43

    Google Scholar 

  30. 30.

    Hatori K, Camargos G, Chatterjee M, Faot F, Sasaki K, Duyck J, Vandamme K (2015) Single and combined effect of high-frequency loading and bisphosphonate treatment on the bone micro-architecture of ovariectomized rats. Osteoporos Int 26:303–313

    CAS  PubMed  Google Scholar 

  31. 31.

    Camargos G, Bhattacharya P, Van Lenthe G, Del Bel Cury A, Naert I, Duyck J, Vandamme K (2015) Mechanical competence of ovariectomy-induced compromised bone after single or combined treatment with high-frequency loading and bisphosphonates. Sci Rep 5:10795

    CAS  PubMed  Google Scholar 

  32. 32.

    Sasaki H, Miyakoshi N, Kasukawa Y, Maekawa S, Noguchi H, Kamo K, Shimada Y (2010) Effects of combination treatment with alendronate and vitamin K2 on bone mineral density and strength in ovariectomized mice. J Bone Miner Metab 28:403–409

    CAS  PubMed  Google Scholar 

  33. 33.

    Moradi A, Kheirollahkhani Y, Fatahi P, Abdollahifar MA, Amini A, Naserzadeh P, Ashtari K, Ghoreishi SK, Chien S, Rezaei F, Fridoni M, Bagheri M, Taheri S, Bayat M (2019) An improvement in acute wound healing in mice by the combined application of photobiomodulation and curcumin-loaded iron particles. Lasers Med Sci 34:779–791

    PubMed  Google Scholar 

  34. 34.

    Mostafavinia A, Amini A, Ghorishi SK, Pouriran R, Bayat M (2016) The effects of dosage and the routes of administrations of streptozotocin and alloxan on induction rate of type1 diabetes mellitus and mortality rate in rats. Lab Anim Res 32:160–165

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Kouhkheil R, Fridoni M, Piryaei A, Taheri S, Chirani AS, Anarkooli IJ, Nejatbakhsh R, Shafikhani S, Schuger LA, Reddy VB (2018) The effect of combined pulsed wave low-level laser therapy and mesenchymal stem cell-conditioned medium on the healing of an infected wound with methicillin-resistant Staphylococcal aureus in diabetic rats. J Cell Biochem 119:5788–5797

    CAS  PubMed  Google Scholar 

  36. 36.

    West M, Slomianka L, Gundersen HJG (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482–497

    CAS  PubMed  Google Scholar 

  37. 37.

    Amini A, Pouriran R, Abdollahifar MA, Abbaszadeh HA, Ghoreishi SK, Chien S, Bayat M (2018) Stereological and molecular studies on the combined effects of photobiomodulation and human bone marrow mesenchymal stem cell conditioned medium on wound healing in diabetic rats, Journal of photochemistry and photobiology. B Biol 182:42–51

    CAS  Google Scholar 

  38. 38.

    A. Amini, H. Soleimani, M.A. Abdollhifar (2019) Stereological and gene expression examinations on the combined effects of photobiomodulation and curcumin on wound healing in type one diabetic rats

  39. 39.

    West MJ, Slomianka L, Gundersen HJ (1991) Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482–497

    CAS  PubMed  Google Scholar 

  40. 40.

    Zhao J, Li YG, Deng KQ, Yun P, Gong T (2017) Therapeutic effects of static magnetic field on wound healing in diabetic rats. J Diabetes Res 2017:6305370

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Choi HMC, Cheung AKK, Ng GYF, Cheing GLY (2018) Effects of pulsed electromagnetic field (PEMF) on the tensile biomechanical properties of diabetic wounds at different phases of healing. PLoS One 13:e0191074

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    Komi DEA, Khomtchouk K, Santa Maria PL (2019) A Review of the contribution of mast cells in wound healing: involved molecular and cellular mechanisms. Clin Rev Allergy Immunol

  43. 43.

    Nishikori Y, Shiota N, Okunishi H (2014) The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice. Arch Dermatol Res 306:823–835

    CAS  PubMed  Google Scholar 

  44. 44.

    Tellechea A, Bai S, Dangwal S, Theocharidis G, Nagai M, Koerner S, Cheong JE, Bhasin S, Shih TY, Zheng Y, Zhao W, Zhang C, Li X, Kounas K, Panagiotidou S, Theoharides T, Mooney D, Bhasin M, Sun L, Veves A (2019) Topical application of a mast cell stabilizer improves impaired diabetic wound healing. J Investig Dermatol

  45. 45.

    Conti P, Ronconi G, Kritas SK, Caraffa A, Theoharides TC (2018) Activated mast cells mediate low-grade inflammation in type 2 diabetes: interleukin-37 could be beneficial. Can J Diabetes 42:568–573

    PubMed  Google Scholar 

  46. 46.

    Shi MA, Shi G-P (2012) Different roles of mast cells in obesity and diabetes: lessons from experimental animals and humans. Front Immunol 3:7

    PubMed  PubMed Central  Google Scholar 

  47. 47.

    Rapala K, Laato M, Niinikoski J, Kujari H, Söder O, Mauviel A, Pujol J-P (1991) Tumor necrosis factor alpha inhibits wound healing in the rat. Eur Surg Res 23:261–268

    CAS  PubMed  Google Scholar 

  48. 48.

    Rapala K (1996) The effect of tumor necrosis factor-alpha on wound healing. An experimental study, in: Annales chirurgiae et gynaecologiae. Supplementum, pp. 1-53

  49. 49.

    Nishioka MA, Pinfildi CE, Sheliga TR, Arias VE, Gomes HC, Ferreira LM (2012) LED (660 nm) and laser (670 nm) use on skin flap viability: angiogenesis and mast cells on transition line. Lasers Med Sci 27:1045–1050

    PubMed  Google Scholar 

  50. 50.

    Falanga V (2005) Wound healing and its impairment in the diabetic foot. Lancet 366:1736–1743

    PubMed  Google Scholar 

  51. 51.

    Bagheri M, Amini A, Abdollahifar MA, Ghoreishi SK, Piryaei A, Pouriran R, Chien S, Dadras S, Rezaei F, Bayat M (2018) Effects of photobiomodulation on degranulation and number of mast cells and wound strength in skin wound healing of streptozotocin-induced diabetic rats. Photomed Laser Surg 36:415–423

    CAS  PubMed  Google Scholar 

  52. 52.

    Kouhkheil R, Fridoni M, Abdollhifar MA, Amini A, Bayat S, Ghoreishi SK, Chien S, Kazemi M, Bayat M (2019) Impact of photobiomodulation and condition medium on mast cell counts, degranulation, and wound strength in infected skin wound healing of diabetic rats. Photobiomodulat Photomed Laser Surg 37:706–714

    Google Scholar 

  53. 53.

    Avci P, Gupta A, Sadasivam M, Vecchio D, Pam Z, Pam N, Hamblin MR (2013) Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring. Seminars Cutaneous Med Surg 32:41–52

    Google Scholar 

  54. 54.

    Tiwari S, Pratyush DD, Gupta SK, Singh SK (2014) Significance of surgical intervention in the management of diabetic foot infections, in: Microbiology for Surgical Infections, Elsevier, pp. 251-266

  55. 55.

    Hidayat M, Maha Y, Wasim H (2015) Effect of melatonin on serum glucose and body weight in streptozotocin induced diabetes in albino rats. J Ayub Med Coll Abbottabad 27:274–276

    PubMed  Google Scholar 

  56. 56.

    Rebolledo-Solleiro D, Fernandez-Guasti A (2018) Influence of sex and estrous cycle on blood glucose levels, body weight gain, and depressive-like behavior in streptozotocin-induced diabetic rats. Physiol Behav 194:560–567

    CAS  PubMed  Google Scholar 

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Correspondence to Sufan Chien or Mohammad Bayat.

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Soleimani, H., Amini, A., Abdollahifar, MA. et al. Combined effects of photobiomodulation and curcumin on mast cells and wound strength in wound healing of streptozotocin-induced diabetes in rats. Lasers Med Sci 36, 375–386 (2021).

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  • Diabetes mellitus
  • Photobiomodulation
  • Curcumin
  • Mast cell
  • Histology
  • Tensiometric properties
  • Rat