References

Silva PAO, Lima SMDF, Almeida JAD Systemic conditions of diabetic patients diagnosed with apical periodontitis. RGO-Revista Gaúcha de Odontologia. 2021; 69

Mobasseri M, Shirmohammadi M, Amiri T Prevalence and incidence of type 1 diabetes in the world: a systematic review and meta-analysis. Health promotion perspectives. 2020; 10:(2)

Babaei S, Ansarihadipour H, Nakhaei M Effect of Omegaven on mast cell concentration in diabetic wound healing. J Tissue Viability. 2017; 26:(2)125-130 https://doi.org/10.1016/j.jtv.2016.12.001

Aichele K, Bubel M, Deubel G Bromelain down-regulates myofibroblast differentiation in an in vitro wound healing assay. Naunyn Schmiedebergs Arch Pharmacol. 2013; 386:(10)853-863 https://doi.org/10.1007/s00210-013-0890-z

Ávalos-Flores E, López-Castillo LM, Wielsch N Protein extract of Bromelia karatas L. rich in cysteine proteases (ananain-and bromelain-like) has antibacterial activity against foodborne pathogens Listeria monocytogenes and Salmonella Typhimurium. Folia Microbiologica. 2022; 67:(1)1-13

Hoba E, Lakra R, Kiran MS, Korrapati PS Fabrication of core–shell nanofibers for controlled delivery of bromelain and salvianolic acid B for skin regeneration in wound therapeutics. Biomedical Materials. 2017; 12:(3)

Douaiher J, Succar J, Lancerotto L Development of mast cells and importance of their tryptase and chymase serine proteases in inflammation and wound healing. Adv Immunol. 2014; 122:211-252 https://doi.org/10.1016/B978-0-12-800267-4.00006-7

Babaei S, Bayat M Effect of pentoxifylline administration on mast cell numbers and degranulation in a diabetic and normoglycemic rat model wound healing. Iran Red Crescent Med J. 2012; 14:(8)483-487

Guo S, DiPietro LA Factors affecting wound healing. J Dent Res. 2010; 89:(3)219-229 https://doi.org/10.1177/0022034509359125

Everett E, Mathioudakis N Update on management of diabetic foot ulcers. Annals of the New York Academy of Sciences. 2018; 1411:(1)153-65

Chang CF, Chang CC, Hwang SL, Chen MY Effects of Buerger exercise combined health-promoting program on peripheral neurovasculopathy among community residents at high risk for diabetic foot ulceration. Worldviews on Evidence-Based Nursing. 2015; 12:(3)145-53

Galli SJ, Tsai M IgE and mast cells in allergic disease. Nat Med. 2012; 18:(5)693-704 https://doi.org/10.1038/nm.2755

Aponte-López A, Fuentes-Pananá EM, Cortes-Muñoz D, Muñoz-Cruz S Mast cell, the neglected member of the tumor microenvironment: role in breast cancer. Journal of immunology research. 2018; 2018

Dong J, Chen L, Zhang Y Mast cells in diabetes and diabetic wound healing. Advances in Therapy. 2020; 37:(11)4519-37

Aller MA, Arias N, Martínez V The gestational power of mast cells in the injured tissue. Inflamm Res. 2018; 67:(2)111-116 https://doi.org/10.1007/s00011-017-1108-5

Komi DEA, Khomtchouk K, Santa Maria PL A review of the contribution of mast cells in wound healing: involved molecular and cellular mechanisms. Clinical Reviews in Allergy & Immunology. 2020; 58:(3)298-312

Lourenço CB, Ataide JA, Cefali LC Evaluation of the enzymatic activity and stability of commercial bromelain incorporated in topical formulations. Int J Cosmet Sci. 2016; 38:(5)535-540 https://doi.org/10.1111/ics.12308

Silva-López R, Gonçalves R Therapeutic proteases from plants: biopharmaceuticals with multiple applications. J Appl Biotechnol Bioeng. 2019; 6:(2)101-109

Tan Y, Li P Bromelain has significant clinical benefits after extraction of the third molar during chemotherapy in patients with hematologic tumor. Oncology letters. 2018; 15:(3)2962-2966

Rosenberg L, Krieger Y, Silberstein E Selectivity of a bromelain based enzymatic debridement agent: a porcine study. Burns. 2012; 38:(7)1035-1040 https://doi.org/10.1016/j.burns.2012.02.011

Donath F, Mai I, Maurer A Dose-related bioavailability of bromelain and trypsin after repeated oral administration. Clin Pharmacol Ther. 1997; 61:(2)

Lorkowski G Gastrointestinal absorption and biological activities of serine and cysteine proteases of animal and plant origin: review on absorption of serine and cysteine proteases. Int J Physiol Pathophysiol Pharmacol. 2012; 4:(1)

Samuel AR, Nazar N Efficacy of Bromelain versus Aceclofenac on post-operative analgesia following dental extractions-a randomised controlled clinical trail. J Pharmaceutical Sciences Research. 2019; 11:(8)3006-3010

de Lencastre Novaes LC, Jozala AF, Lopes AM Stability, purification, and applications of bromelain: a review. Biotechnol Prog. 2016; 32:(1)5-13 https://doi.org/10.1002/btpr.2190

Colosimo S, Balzani E, Cioni R Supplementation with anti-inflammatory nutraceutical products in the management of chronic pelvic pain: a narrative review. Current Topics in Nutraceutical Research. 2022; 20:(2)

Sahbaz A, Aynioglu O, Isik H Bromelain: a natural proteolytic for intra-abdominal adhesion prevention. Int J Surg. 2015; 14:7-11 https://doi.org/10.1016/j.ijsu.2014.12.024

Pavan R, Jain S, Kumar A Properties and therapeutic application of bromelain: a review. Biotechnol Res Int. 2012; 2012 https://doi.org/10.1155/2012/976203

Babas S, Luka C, Istifanus G, Mayel M Determination of the antidiabetic property of the aqueous extract of biophytum sensitivum on streptozotocin induced diabetic rats. GSJ. 2020; 8:(8)

Kristová V, Líšková S, Sotníková R Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats. Physiol Res. 2008; 57:(3)491-494 https://doi.org/10.33549/physiolres.931506

Osman W, Mohammed MS, Khalid HS HPTLC fingerprint profile and identification of antidiabetic and antioxidant leads from Bauhinia rufescens L. Advances in Pharmacological and Pharmaceutical Sciences. 2020; 2020

Babaei S, Bayat M, Nouruzian M, Bayat M Pentoxifylline improves cutaneous wound healing in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2013; 700:(1–3)165-172 https://doi.org/10.1016/j.ejphar.2012.11.024

Borrelli F, Capasso R, Severino B Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice. Neurogastroenterol Motil. 2011; 23:(8)745-e331 https://doi.org/10.1111/j.1365-2982.2011.01735.x

Fathi AN, Sakhaie MH, Babaei S Use of bromelain in cutaneous wound healing in streptozocin-induced diabetic rats: an experimental model. J Wound Care. 2020; 29:(9)488-495 https://doi.org/10.12968/jowc.2020.29.9.488

Chang AC, Dearman B, Greenwood JE A comparison of wound area measurement techniques: visitrak versus photography. Eplasty. 2011; 11

Weibel ER Morphometry: stereological theory and practical methods.: CRC Press; 2020

Zheng J, Zhang J, Tian Y Quantification of ovarian granulosa cells and different level follicles in the mouse ovary using stereology method, for potential application in 3d bioengineered ovary. 2020; https://doi.org/10.21203/rs.3.rs-26397/v1

Mutsaddi S, Kotrashetti V, Nayak R, Pattanshetty S Comparison of histochemical staining techniques for detecting mast cells in oral lesions. Biotechnic & Histochemistry. 2019; 94:(6)459-468

de Oliveira RC, Wilson SE Fibrocytes, wound healing, and corneal fibrosis. Invest Ophthalmol Vis Sci. 2020; 61:(2) https://doi.org/10.1167/iovs.61.2.28

Pradhan L, Cai X, Wu S Gene expression of pro-inflammatory cytokines and neuropeptides in diabetic wound healing. J Surg Res. 2011; 167:(2)336-342 https://doi.org/10.1016/j.jss.2009.09.012

Babaei S, Nakhaei M, Ansarihadipour H Omegaven improves skin morphometric indices in diabetic rat model wound healing. J Am Coll Clin Wound Spec. 2017; 9:(1–3)39-45 https://doi.org/10.1016/j.jccw.2018.04.001

Nedeau AE, Bauer RJ, Gallagher K A CXCL5- and bFGF-dependent effect of PDGF-B-activated fibroblasts in promoting trafficking and differentiation of bone marrow-derived mesenchymal stem cells. Exp Cell Res. 2008; 314:(11–12)2176-2186 https://doi.org/10.1016/j.yexcr.2008.04.007

Wu SY, Hu W, Zhang B Bromelain ameliorates the wound microenvironment and improves the healing of firearm wounds. J Surg Res. 2012; 176:(2)503-509 https://doi.org/10.1016/j.jss.2011.11.1027

Ng MF The role of mast cells in wound healing. Int Wound J. 2010; 7:(1)55-61 https://doi.org/10.1111/j.1742-481X.2009.00651.x

Soucek L, Lawlor ER, Soto D Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat Med. 2007; 13:(10)1211-1218 https://doi.org/10.1038/nm1649

Metcalfe DD, Baram D, Mekori YA Mast cells. Physiol Rev. 1997; 77:(4)1033-1079 https://doi.org/10.1152/physrev.1997.77.4.1033

Caslin HL, Kiwanuka KN, Haque TT Controlling mast cell activation and homeostasis: work influenced by Bill Paul that continues today. Frontiers in Immunology. 2018; 9

Ertuğrul T, Tutuncu Ş, Ozdemır B, Delıce N Possible effect of thymoquinone on mast cell number and chymase, IL-4 and IFN-γ expression in rat spleen. Med Weter. 2021; 77:(10)484-490

Kimura T, Sugaya M, Blauvelt A Delayed wound healing due to increased interleukin-10 expression in mice with lymphatic dysfunction. Journal of Leukocyte Biology. 2013; 94:(1)137-145

Bagheri M, Amini A, Abdollahifar M-A Effects of photobiomodulation on degranulation and number of mast cells and wound strength in skin wound healing of streptozotocin-induced diabetic rats. Photomedicine and Laser Surgery. 2018; 36:(8)415-423

Moon TC, Befus AD, Kulka M Mast cell mediators: their differential release and the secretory pathways involved. Front Immunol. 2014; 5 https://doi.org/10.3389/fimmu.2014.00569

Nakahashi-Oda C, Tahara-Hanaoka S, Shoji M Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor. J Exp Med. 2012; 209:(8)1493-1503 https://doi.org/10.1084/jem.20120096

Conti P, D'Ovidio C, Conti C Progression in migraine: role of mast cells and pro-inflammatory and anti-inflammatory cytokines. Eur J Pharmacol. 2019; 844:87-94 https://doi.org/10.1016/j. ejphar.2018.12.004

Effect of bromelain on mast cell numbers and degranulation in diabetic rat wound healing

01 August 2022

Abstract

Objective:

Many studies have revealed the prominent roles of mast cells in wound healing, including inflammatory reactions, angiogenesis and extracellular matrix reabsorption. In the present study, we aimed to assess the probable therapeutic features of bromelain on wound contraction and mast cell degranulation in wound healing in experimental diabetic animals.

Method:

Male rats were grouped as control, vehicle and experiment. Skin wounds were generated in all groups. Treatments were applied with distilled water and with bromelain (BR) intraperitoneally in the vehicle and experimental groups, respectively. Following skin wound generation, animals were euthanised on days 3, 5, 7 and 15. We gathered 16,800 microscopic images to count the mast cells and degranulation level (Image J software). The wound contraction index was assessed both microscopically (Image J software) and macroscopically (time-lapse photography). The meshwork evaluation method was used to assess wound healing.

Results:

Time-lapse photography revealed that the BR significantly (p<0.05) accelerated wound contraction and healing. BR significantly (p<0.05) increased the total number of mast cells in all experimental groups on days 5 and 7. The count of grade III (degranulated) mast cells was reduced significantly (p<0.05) on days 5 and 7 in experimental groups compared to control and vehicle groups.

Conclusion:

In this study, the rate of wound healing was accelerated considerably following BR administration. In addition, this agent decreased the count of degranulated mast cells, leading to wound contraction and healing.

The total number of people with diabetes worldwide is projected to rise from 171 million in 2000 to 366 million in 2030, resulting in a prevalence of diabetes of 4.4%. The prevalence of diabetes is more common in men and increases with age, especially from the age of 65 years.1

Approximately 15 per 100,000 people (prevalence of 9.5%, 95% CI: 0.07 to 0.12) were diagnosed with type 1 diabetes globally.2 Wound healing in patients with diabetes is an intricate pathway, and globally, 15% of these patients have diabetes-related complications, such as foot wounds.2,3

Bromelain, as a herbal extract, is rich in cysteine proteases and is collected from the Bromeliaceae family. Bromelain has therapeutic effects, including anti-inflammatory and immunomodulatory characteristics.4,5

In the present study, we aimed to assess the probable therapeutic features of bromelain on wound contraction and mast cell degranulation in wound healing in experimental diabetic animals.6,7 The meshwork evaluation method was used to assess wound healing.3,8

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