Skip to main content

Advertisement

SpringerLink
Log in

Accelerated Wound Healing Potential of Nisin in Streptozotocin Induced Diabetes Mellitus in Wistar Rats

  • Published:
International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

About twenty percent of diabetic patients develop diabetic wounds and diabetic foot gradually resulting in severe infections and lower limb complications. Antimicrobial peptides (AMPs) are potential candidates exploited for their wound healing properties. Nisin a class I bacteriocin having GRAS (Generally recognized as safe) status has been demonstrated to have wound healing effects. We established a diabetic wound excision model in rats via streptozotocin administration and evaluated the efficacy of nisin in pacing up wound healing in terms of wound closure parameters, collagen content, histopathological and topographical alterations, oxidant and antioxidative environment of wounded tissue, cytokines and growth factors expressions. Significant increase in the levels of hydroxyproline, hexosamine and hexuronic acid upon nisin therapy directly pointed towards the increased collagen content. Significant alterations in wound diameter, levels of IL-1, IL-6, TNF-α and transcriptional levels of VEGF and EGF were observed in treated rats. H&E, picro-sirius red staining and scanning electron micrographic studies of treated skin tissues revealed the restoration of different layers of skin tissue along with increase in collagen content and skin regeneration. Biochemical parameters indicated increase in levels of antioxidants and reduced tlevels of free radicals upon therapy thereby improving the oxidative stress prevailing in wound microenvironment. The present study established nisin as a wound healing promoter in diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Badr G (2013) Camel whey protein enhances diabetic wound healing in a streptozotocin-induced diabetic mouse model: the critical role of β-Defensin-1,-2 and-3. Lipids Health Dis 12:1–11

    Article  Google Scholar 

  • Bitter T (1962) A modified uronic acid carbazole reaction. Anal Biochem 4:330–334

    Article  CAS  PubMed  Google Scholar 

  • Carretero M, Escámez MJ, García M et al (2008) In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. J Investig Dermatol 128:223–236

    Article  CAS  PubMed  Google Scholar 

  • Cohen M, Shilo S, Zuckerman-Levin N et al (2015) Diabetic ketoacidosis in the pediatric population with type 1 diabetes. Major topics in type 1 diabetes. Intech, London, pp 95–119

    Google Scholar 

  • Elosta A, Ghous T, Ahmed N (2012) Natural products as anti-glycation agents: possible therapeutic potential for diabetic complications. Curr Diabetes Rev 8:92–616

    Article  CAS  PubMed  Google Scholar 

  • Elson LA, Morgan WTJ (1933) A colorimetric method for the determination of glucosamine and chondrosamine. Biochem J 27:1824–1828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eming SA, Martin P, Tomic-Canic M (2014) Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 6:265sr6

    Article  PubMed  PubMed Central  Google Scholar 

  • Esposito S, Leone S, Noviello S et al (2008) Foot infections in diabetes (DFIs) in the out-patient setting: an Italian multicentre observational survey. Diabet Med 25:979–984

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Gautam MK, Purohit V, Agarwal M et al (2014) In vivo healing potential of Aegle marmelos in excision, incision, and dead space wound models. Sci World J 2014:1–9

    Article  Google Scholar 

  • Gomes D, Santos R, Soares R et al (2020) Pexiganan in combination with nisin to control polymicrobial diabetic foot infections. Antibiotics (basel) 9:128

    Article  CAS  Google Scholar 

  • Gonzalez AC, Costa TF, Andrade ZA et al (2016) Wound healing-a literature review. An Bras Dermatol 91:614–620

    Article  PubMed  PubMed Central  Google Scholar 

  • Green LC, Wagner DA, Glogowski J et al (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126:131–138

    Article  CAS  PubMed  Google Scholar 

  • Heunis TD, Smith C, Dicks LM (2013) Evaluation of a nisin-eluting nanofiber scaffold to treat Staphylococcus aureus-induced skin infections in mice. Antimicrob Agent Chemother 57:3928–3935

    Article  CAS  Google Scholar 

  • Hirsch T, Spielmann M, Zuhaili B et al (2009) Human beta-defensin-3 promotes wound healing in infected diabetic wounds. J Gene Med 11:220–228

    Article  CAS  PubMed  Google Scholar 

  • Junqueira LCU, Bignolas G, Brentani RR (1979) Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochem J 11:447–455

    Article  CAS  PubMed  Google Scholar 

  • Kant V, Gopal A, Pathak NN et al (2014) Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats. Intl Immunopharmacol 20:322–330

    Article  CAS  Google Scholar 

  • Kono Y (1978) Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 186:189–195

    Article  CAS  PubMed  Google Scholar 

  • Lipsky B, Holroyd K, Zasloff M (2009) Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers: a randomized, controlled, double-blinded, multicenter trial of pexiganan cream. Clin Infect Dis 47:1537–1545

    Article  Google Scholar 

  • Liu B, Fu R, Duan Z, Zhu C, Deng J, Fan D (2022) Ionic liquid-based non-releasing antibacterial, anti-inflammatory, high-transparency hydrogel coupled with electrical stimulation for infected diabetic wound healing. Composite B 1(236):109804

    Article  Google Scholar 

  • Lück H (1965) Catalase. In methods of enzymatic. Analysis 1965:885–894

    Google Scholar 

  • Luo Y, Song Y (2021) Mechanism of antimicrobial peptides: antimicrobial, anti-inflammatory and antibiofilm activities. Int J Mol Sci 21:11401

    Article  Google Scholar 

  • Małaczewska J, Kaczorek-Łukowska E (2021) Nisin-A lantibiotic with Immunomodulatory properties: a review. Peptides 137:170479

    Article  PubMed  Google Scholar 

  • Malvisi M, Stuknytė M, Magro G et al (2016) Antibacterial activity and immunomodulatory effects on a bovine mammary epithelial cell line exerted by nisin A-producing Lactococcus lactis strains. J Dairy Sci 99:2288–2296

    Article  CAS  PubMed  Google Scholar 

  • Mbara KC, Rambharose S, Baijnath H, Nlooto M, Owira PM (2022) Antidiabetic effects of Psidium x durbanensis Baijnath & Ramcharun ined (Myrtaceae) leaf extract on streptozotocin induced diabetes in rats. J Ethnopharmacol 14:115542

    Article  Google Scholar 

  • Mcinnes RL, Cullen BM, Hill KE et al (2014) Contrasting host immuno-inflammatory response to bacterial challenge within venous and diabetic ulcers. Wound Repair Regen 22:58–69

    Article  PubMed  Google Scholar 

  • Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochimica Et Biophysica Acta (BBA) 582:67–78

    Article  CAS  Google Scholar 

  • Mouritzen MV, Andrea A, Qvist K et al (2019) Immunomodulatory potential of Nisin A with application in wound healing. Wound Repair Regen 27:650–660

    Article  PubMed  Google Scholar 

  • Murthy S, Gautam MK, Goel S et al (2013) Evaluation of in vivo wound healing activity of Bacopa monniera on different wound model in rats. Biomed Res Int 2013:1–9

    Article  Google Scholar 

  • Oguntibeju J (2019) Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. Int J Physiol Pathophysiol Pharmacol 11:45–63

    CAS  PubMed  PubMed Central  Google Scholar 

  • Patel S, Srivastava S, Singh MR et al (2019) Mechanistic insight into diabetic wounds: pathogenesis, molecular targets and treatment strategies to pace wound healing. Biomed Pharmacother 112:108615

    Article  CAS  PubMed  Google Scholar 

  • Pfalzgraff A, Brandenburg K, Weindl G (2018) Antimicrobial peptides and their therapeutic potential for bacterial skin infections and wounds. Front Pharmacol 9:281

    Article  PubMed  PubMed Central  Google Scholar 

  • Pouget C, Dunyach-Remy C, Pantel A et al (2020) Biofilms in diabetic foot ulcers: significance and clinical relevance. Microorganisms 8:1580

    Article  PubMed Central  Google Scholar 

  • Preet S, Bharati S, Panjeta A et al (2015) Effect of nisin and doxorubicin on DMBA induced skin carcinogenesis–a possible adjunct therapy. Tumor Biol 36:8301–8308

    Article  CAS  Google Scholar 

  • Preet S, Kaur J, Raza K (2021) Nisin loaded carbopol gel against Pseudomonas aeruginosa infected third-degree burns: a therapeutic intervention. Wound Repair Regen 29:711–724

    Article  PubMed  Google Scholar 

  • Rahman N, Rahman H, Haris M et al (2017) Wound healing potentials of Thevetia peruviana: antioxidants and inflammatory markers criteria. J Tradit Complement Med 7:519–525

    Article  PubMed  PubMed Central  Google Scholar 

  • Santos R, Ruza D, Cunha E et al (2019) Diabetic foot infections: application of a nisin biogel to complement the activity of conventional antibiotics and antiseptics against Staphylococcus aureus biofilms. PLoS ONE 14:e0220000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szkudelski T (2001) The mechanism of alloxan and streptozotocin action in B cells of the rat Pancreas. Physiol Res 50:537–546

    CAS  PubMed  Google Scholar 

  • Thangarajah H, Chang YD (2009) The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues. Proc Natl Acad Sci USA 106:13505–13510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wills E (1966) Mechanisms of lipid peroxide formation in animal tissues. Biochem J 99:667–676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xue M, Jackson CJ (2015) Extracellular Matrix Reorganization During Wound Healing and its Impact on Abnormal Scarring. Adv Wound Care 4:119–136

    Article  Google Scholar 

Download references

Funding

This work was supported by the Science and Engineering Research Board, Department of Science& Technology, Government of India (EEQ/2017/000540).

Author information

Authors and Affiliations

  1. Department of Biophysics, Basic Medical Sciences Block II, Sector-25, South Campus, Panjab University, Chandigarh, 160014, India

    Simran Preet, Shivani Sharma, Anshul Panjeta & Jasleen Kaur

  2. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia

    Abdulrahman Alshammari & Metab Alharbi

  3. Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, Saudi Arabia

    Saud Almawash

Authors
  1. Simran Preet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shivani Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anshul Panjeta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jasleen Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abdulrahman Alshammari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Metab Alharbi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Saud Almawash
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design of the study: Simran Preet, execution and collection of the data: Shivani Sharma, Data collection, data analysis and original draft: Anshul Panjeta, Execution of staining experiments and data interpretation: Jasleen Kaur, Statistical analysis: Abdulrahman Alshammari, Metab Alharbi, Manuscript review for grammatical errors and interpreted the histology results: Saud Almawash.

Corresponding author

Correspondence to Simran Preet.

Ethics declarations

Competing interests

The authors declare no competing interests.

Conflict of interest

Simran Preet, Shivani Sharma, Anshul Panjeta, Jasleen Kaur, Abdulrahman Alshammari, Metab Alharbi and Saud Almawash declare that they have no competing interests.

Ethical Approval

All the experimental protocols were approved by The Institutional Animal Ethical Committee of Panjab University, Chandigarh (India) (IAEC/2019/357) and in compliance with the ethics guidelines.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Preet, S., Sharma, S., Panjeta, A. et al. Accelerated Wound Healing Potential of Nisin in Streptozotocin Induced Diabetes Mellitus in Wistar Rats. Int J Pept Res Ther 28, 147 (2022). https://doi.org/10.1007/s10989-022-10452-8

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10989-022-10452-8

Keywords

Search

Navigation