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Captopril inhibits matrix metalloproteinase activity and improves dentin bonding durability

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Abstract

Objectives

We investigated the inhibitory effects of captopril on matrix metalloproteinases (MMPs) and its effect as a primer on dentin bonding durability.

Materials and methods

One hundred fifty human third molars were selected. Flat surfaces of the middle dentin were exposed, etched 15 s, and followed by pretreatment with a primer for 60 s, including distilled water (control, the negative control primer), 2% chlorhexidine digluconate (CHD, the positive control primer), and captopril solution. Inhibitory effects of primers on MMPs were evaluated by hydroxyproline and gelatinase activity tests. All primers were applied on dentin followed by bonding. Some of the samples were sliced into slabs, placed in a fluorescent solution containing gelatin, and incubated for in situ zymography. Some were cut into sticks, and after aging for 1 day, 12 months, or 24 months, microtensile bonding strength was tested. Some were cut into slabs, aged for 1 day, 12 months, or 24 months, and taken out for nanoleakage tests to reveal interface defects.

Results

Hydroxyproline and gelatinase activity analyses showed that captopril exerted better inhibitory effects on MMPs, relative to 2% CHD (p < 0.05). A 0.2% captopril aqueous solution (0.2% CapW) was chosen to apply to the dentin. In situ zymography showed that inhibitory effects of captopril on gelatinase were significantly higher compared to 2% CHD (p < 0.01). Microtensile strength revealed that the bonding effects of the 0.2% CapW group lasted longer, compared to the control and 2% CHD groups (p < 0.05). Interface defects, detected by nanoleakage, were significantly reduced in the 0.2% CapW group, compared to the control and 2% CHD groups (p < 0.05).

Conclusions

Captopril inhibits dentin MMP activities and effectively improves dentin bonding durability.

Clinical relevance

Captopril is a promising dentin bonding primer for improving bonding durability.

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References

  1. Tjaderhane L (2015) Dentin bonding: can we make it last? Oper Dent 40:4–18. https://doi.org/10.2341/14-095-BL

    Article  PubMed  Google Scholar 

  2. Astvaldsdottir A, Dagerhamn J, van Dijken JW, Naimi-Akbar A, Sandborgh-Englund G, Tranaeus S, Nilsson M (2015) Longevity of posterior resin composite restorations in adults - a systematic review. J Dent 43:934–954. https://doi.org/10.1016/j.jdent.2015.05.001

    Article  PubMed  Google Scholar 

  3. Toledano M, Osorio R, Osorio E, Medina-Castillo AL, Toledano-Osorio M, Aguilera FS (2017) Ions-modified nanoparticles affect functional remineralization and energy dissipation through the resin-dentin interface. J Mech Behav Biomed Mater 68:62–79. https://doi.org/10.1016/j.jmbbm.2017.01.026

    Article  PubMed  Google Scholar 

  4. Wang Y, Spencer P (2002) Quantifying adhesive penetration in adhesive/dentin interface using confocal Raman microspectroscopy. J Biomed Mater Res 59:46–55

    Article  Google Scholar 

  5. Frassetto A, Breschi L, Turco G, Marchesi G, Di Lenarda R, Tay FR, Pashley DH, Cadenaro M (2016) Mechanisms of degradation of the hybrid layer in adhesive dentistry and therapeutic agents to improve bond durability–a literature review. Dental materials: official publication of the Academy of Dental Materials 32:e41-53. https://doi.org/10.1016/j.dental.2015.11.007

    Article  Google Scholar 

  6. Breschi L, Maravic T, Cunha SR, Comba A, Cadenaro M, Tjaderhane L, Pashley DH, Tay FR, Mazzoni A (2018) Dentin bonding systems: from dentin collagen structure to bond preservation and clinical applications. Dent Mater 34:78–96. https://doi.org/10.1016/j.dental.2017.11.005

    Article  PubMed  Google Scholar 

  7. Mazzoni A, Tjaderhane L, Checchi V, Di Lenarda R, Salo T, Tay FR, Pashley DH, Breschi L (2015) Role of dentin MMPs in caries progression and bond stability. J Dent Res 94:241–251. https://doi.org/10.1177/0022034514562833

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kumar L, Cox CR and Sarkar SK (2019) Matrix metalloprotease-1 inhibits and disrupts Enterococcus faecalis biofilms. PloS one 14. https://doi.org/10.1371/journal.pone.0210218

  9. Ou QM, Hu Y, Yao SQ, Wang Y, Lin XF (2018) Effect of matrix metalloproteinase 8 inhibitor on resin-dentin bonds. Dent Mater 34:756–763. https://doi.org/10.1016/j.dental.2018.01.027

    Article  PubMed  Google Scholar 

  10. Mazzoni A, Mannello F, Tay FR, Tonti GA, Papa S, Mazzotti G, Di Lenarda R, Pashley DH, Breschi L (2007) Zymographic analysis and characterization of MMP-2 and -9 forms in human sound dentin. J Dent Res 86:436–440. https://doi.org/10.1177/154405910708600509

    Article  PubMed  Google Scholar 

  11. Mazzoni A, Papa V, Nato F, Carrilho M, Tjaderhane L, Ruggeri A, Gobbi P, Mazzotti G, Tay FR, Pashley DH, Breschi L (2011) Immunohistochemical and biochemical assay of MMP-3 in human dentine. J Dent 39:231–237. https://doi.org/10.1016/j.jdent.2011.01.001

    Article  PubMed  Google Scholar 

  12. Sulkala M, Larmas M, Sorsa T, Salo T, Tjaderhane L (2002) The localization of matrix metalloproteinase-20 (MMP-20, enamelysin) in mature human teeth. J Dent Res 81:603–607. https://doi.org/10.1177/154405910208100905

    Article  PubMed  Google Scholar 

  13. Shailendra M, Bhandari S, Kulkarni S, Janavathi K, Ghatole K (2019) Evaluation of indomethacin as matrix metalloproteases inhibitor in human dentin. J Conserv Dent 22:598–601. https://doi.org/10.4103/JCD.JCD_236_19

    Article  PubMed  Google Scholar 

  14. Tekce N, Tuncer S, Demirci M, Balci S (2016) Do matrix metalloproteinase inhibitors improve the bond durability of universal dental adhesives? Scanning 38:535–544. https://doi.org/10.1002/sca.21293

    Article  PubMed  Google Scholar 

  15. da Silva EM, Rodrigues CUFD, Matos MPD, de Carvalho TR, dos Santos GB, Amaral CM (2015) Experimental etch-and-rinse adhesive systems containing MMP-inhibitors: physicochemical characterization and resin-dentin bonding stability. J Dent 43:1491–1497. https://doi.org/10.1016/j.jdent.2015.10.004

    Article  PubMed  Google Scholar 

  16. Kiuru O, Sinervo J, Vahanikkila H, Anttonen V, Tjaderhane L (2021) MMP inhibitors and dentin bonding: systematic review and meta-analysis. Int J Dent 2021:9949699. https://doi.org/10.1155/2021/9949699

    Article  PubMed  PubMed Central  Google Scholar 

  17. El Gezawi M, Haridy R, Abo Elazm E, Al-Harbi F, Zouch M, Kaisarly D (2018) Microtensile bond strength, 4-point bending and nanoleakage of resin-dentin interfaces: effects of two matrix metalloproteinase inhibitors. J Mech Behav Biomed Mater 78:206–213. https://doi.org/10.1016/j.jmbbm.2017.11.024

    Article  PubMed  Google Scholar 

  18. Sabatini C, Patel SK (2013) Matrix metalloproteinase inhibitory properties of benzalkonium chloride stabilizes adhesive interfaces. Eur J Oral Sci 121:610–616. https://doi.org/10.1111/eos.12089

    Article  PubMed  Google Scholar 

  19. Sabatini C, Pashley DH (2014) Mechanisms regulating the degradation of dentin matrices by endogenous dentin proteases and their role in dental adhesion. A review Am J Dent 27:203–214

    PubMed  Google Scholar 

  20. Osorio R, Yamauti M, Osorio E, Ruiz-Requena ME, Pashley DH, Tay FR, Toledano M (2011) Zinc reduces collagen degradation in demineralized human dentin explants. J Dent 39:148–153. https://doi.org/10.1016/j.jdent.2010.11.005

    Article  PubMed  Google Scholar 

  21. Almahdy A, Koller G, Sauro S, Bartsch JW, Sherriff M, Watson TF, Banerjee A (2012) Effects of MMP inhibitors incorporated within dental adhesives. J Dent Res 91:605–611. https://doi.org/10.1177/0022034512446339

    Article  PubMed  PubMed Central  Google Scholar 

  22. Perdigao J, Reis A, Loguercio AD (2013) Dentin adhesion and MMPs: a comprehensive review. J Esthet Restor Dent 25:219–241. https://doi.org/10.1111/jerd.12016

    Article  PubMed  Google Scholar 

  23. Vallabhdas AK, Kumar CNV, Kabbinale P, Nayak R, Rajakumari M, Shilpa T (2018) Evaluation of hybrid layer and bonding interface after water storage with and without the usage of 2% chlorhexidine: a scanning electron microscope study. J Contemp Dent Pract 19:52–59. https://doi.org/10.5005/jp-journals-10024-2211

    Article  PubMed  Google Scholar 

  24. Zheng X, Hu J, Chen Y, Zhu Y, Chen H (2012) AFM study of the effects of collagenase and its inhibitors on dentine collagen fibrils. J Dent 40:163–171. https://doi.org/10.1016/j.jdent.2011.12.009

    Article  PubMed  Google Scholar 

  25. Seseogullari-Dirihan R, Mutluay MM, Vallittu P, Pashley DH, Tezvergil-Mutluay A (2015) Effect of pretreatment with collagen crosslinkers on dentin protease activity. Dent Mater 31:941–947. https://doi.org/10.1016/j.dental.2015.05.002

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hass V, Luque-Martinez IV, Gutierrez MF, Moreira CG, Gotti VB, Feitosa VP, Koller G, Otuki MF, Loguercio AD, Reis A (2016) Collagen cross-linkers on dentin bonding: stability of the adhesive interfaces, degree of conversion of the adhesive, cytotoxicity and in situ MMP inhibition. Dent Mater 32:732–741. https://doi.org/10.1016/j.dental.2016.03.008

    Article  PubMed  Google Scholar 

  27. Sezinando A, Luque-Martinez I, Munoz MA, Reis A, Loguercio AD, Perdigao J (2015) Influence of a hydrophobic resin coating on the immediate and 6-month dentin bonding of three universal adhesives. Dent Mater 31:e236–e246. https://doi.org/10.1016/j.dental.2015.07.002

    Article  PubMed  Google Scholar 

  28. Kim J, Uchiyama T, Carrilho M, Agee KA, Mazzoni A, Breschi L, Carvalho RM, Tjaderhane L, Looney S, Wimmer C, Tezvergil-Mutluay A, Tay FR, Pashley DH (2010) Chlorhexidine binding to mineralized versus demineralized dentin powder. Dent Mater 26:771–778. https://doi.org/10.1016/j.dental.2010.04.001

    Article  PubMed  PubMed Central  Google Scholar 

  29. Seseogullari-Dirihan R, Apollonio F, Mazzoni A, Tjaderhane L, Pashley D, Breschi L, Tezvergil-Mutluay A (2016) Use of crosslinkers to inactivate dentin MMPs. Dent Mater 32:423–432. https://doi.org/10.1016/j.dental.2015.12.012

    Article  PubMed  Google Scholar 

  30. Natesh R, Schwager SL, Evans HR, Sturrock ED, Acharya KR (2004) Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry 43:8718–8724. https://doi.org/10.1021/bi049480n

    Article  PubMed  Google Scholar 

  31. Cushman DW, Ondetti MA (1991) History of the design of captopril and related inhibitors of angiotensin converting enzyme. Hypertension 17:589–592

    Article  Google Scholar 

  32. Kast RE, Halatsch ME (2012) Matrix metalloproteinase-2 and -9 in glioblastoma: a trio of old drugs-captopril, disulfiram and nelfinavir-are inhibitors with potential as adjunctive treatments in glioblastoma. Arch Med Res 43:243–247. https://doi.org/10.1016/j.arcmed.2012.04.005

    Article  PubMed  Google Scholar 

  33. Chen Y, Luo Q, Shu C, Li X, Li X (2021) Effect of captopril pretreatment on the dentin bonding durability of self-etch adhesive. Zhejiang Da Xue Xue Bao Yi Xue Ban 50:179–186. https://doi.org/10.3724/zdxbyxb-2021-0116

    Article  PubMed  PubMed Central  Google Scholar 

  34. Liu R, Fang M, Xiao Y, Li F, Yu L, Zhao S, Shen L, Chen J (2011) The effect of transient proanthocyanidins preconditioning on the cross-linking and mechanical properties of demineralized dentin. J Mater Sci Mater Med 22:2403–2411. https://doi.org/10.1007/s10856-011-4430-4

    Article  PubMed  Google Scholar 

  35. Tezvergil-Mutluay A, Agee KA, Hoshika T, Tay FR, Pashley DH (2010) The inhibitory effect of polyvinylphosphonic acid on functional matrix metalloproteinase activities in human demineralized dentin. Acta Biomater 6:4136–4142. https://doi.org/10.1016/j.actbio.2010.05.017

    Article  PubMed  PubMed Central  Google Scholar 

  36. Ozcan S, Seseogullari-Dirihan R, Uctasli M, Tay FR, Pashley DH, Tezuergil-Mutluay A (2015) Effect of polyacrylic acid on dentin protease activities. Dent Mater 31:901–906. https://doi.org/10.1016/j.dental.2015.04.018

    Article  PubMed  Google Scholar 

  37. Shim WJ, Song YK, Hong SH, Jang M (2016) Identification and quantification of microplastics using Nile Red staining. Mar Pollut Bull 113:469–476. https://doi.org/10.1016/j.marpolbul.2016.10.049

    Article  PubMed  Google Scholar 

  38. Mazzoni A, Nascimento FD, Carrilho M, Tersariol I, Papa V, Tjaderhane L, Di Lenarda R, Tay FR, Pashley DH, Breschi L (2012) MMP activity in the hybrid layer detected with in situ zymography. J Dent Res 91:467–472. https://doi.org/10.1177/0022034512439210

    Article  PubMed  PubMed Central  Google Scholar 

  39. Huang HH, Chiu YH, Lee TH, Wu SC, Yang HW, Su KH, Hsu CC (2003) Ion release from NiTi orthodontic wires in artificial saliva with various acidities. Biomaterials 24:3585–3592. https://doi.org/10.1016/S0142-9612(03)00188-1

    Article  PubMed  Google Scholar 

  40. Tay FR, Pashley DH, Yoshiyama M (2002) Two modes of nanoleakage expression in single-step adhesives. J Dent Res 81:472–476

    Article  Google Scholar 

  41. Munoz MA, Luque I, Hass V, Reis A, Loguercio AD, Bombarda NHC (2013) Immediate bonding properties of universal adhesives to dentine. J Dent 41:404–411. https://doi.org/10.1016/j.jdent.2013.03.001

    Article  PubMed  Google Scholar 

  42. Tjaderhane L, Nascimento FD, Breschi L, Mazzoni A, Tersariol ILS, Geraldeli S, Tezvergil-Mutluay A, Carrilho MR, Carvalho RM, Tay FR, Pashley DH (2013) Optimizing dentin bond durability: control of collagen degradation by matrix metalloproteinases and cysteine cathepsins. Dent Mater 29:116–135. https://doi.org/10.1016/j.dental.2012.08.004

    Article  PubMed  Google Scholar 

  43. Montagner AF, Sarkis-Onofre R, Pereira-Cenci T, Cenci MS (2014) MMP inhibitors on dentin stability: a systematic review and meta-analysis. J Dent Res 93:733–743. https://doi.org/10.1177/0022034514538046

    Article  PubMed  PubMed Central  Google Scholar 

  44. Gendron R, Grenier D, Sorsa T, Mayrand D (1999) Inhibition of the activities of matrix metalloproteinases 2, 8, and 9 by chlorhexidine. Clin Diagn Lab Immunol 6:437–439

    Article  Google Scholar 

  45. Li H, Li TB, Li XY, Zhang ZM, Li PL, Li ZL (2015) Morphological effects of MMPs inhibitors on the dentin bonding. Int J Clin Exp Med 8:10793–10803

    PubMed  PubMed Central  Google Scholar 

  46. Hebling J, Pashley DH, Tjaderhane L, Tay FR (2005) Chlorhexidine arrests subclinical degradation of dentin hybrid layers in vivo. J Dent Res 84:741–746. https://doi.org/10.1177/154405910508400811

    Article  PubMed  Google Scholar 

  47. Yamamoto D, Takai S, Hirahara I, Kusano E (2010) Captopril directly inhibits matrix metalloproteinase-2 activity in continuous ambulatory peritoneal dialysis therapy. Clin Chim Acta 411:762–4. https://doi.org/10.1016/j.cca.2010.02.059

    Article  PubMed  Google Scholar 

  48. Yamamoto D, Takai S, Miyazaki M (2008) Inhibitory profiles of captopril on matrix metalloproteinase-9 activity. Eur J Pharmacol 588:277–279. https://doi.org/10.1016/j.ejphar.2008.04.031

    Article  PubMed  Google Scholar 

  49. Sano H, Shono T, Takatsu T, Hosoda H (1994) Microporous dentin zone beneath resin-impregnated layer. Oper Dent 19:59–64

    PubMed  Google Scholar 

  50. Sano H, Yoshiyama M, Ebisu S, Burrow MF, Takatsu T, Ciucchi B, Carvalho R, Pashley DH (1995) Comparative SEM and TEM observations of nanoleakage within the hybrid layer. Oper Dent 20:160–167

    PubMed  Google Scholar 

  51. Sano H, Takatsu T, Ciucchi B, Horner JA, Matthews WG, Pashley DH (1995) Nanoleakage: leakage within the hybrid layer. Oper Dent 20:18–25

    PubMed  Google Scholar 

  52. Yuan Y, Shimada Y, Ichinose S, Tagami J (2007) Qualitative analysis of adhesive interface nanoleakage using FE-SEM/EDS. Dent Mater 23:561–569. https://doi.org/10.1016/j.dental.2006.03.015

    Article  PubMed  Google Scholar 

  53. Young JB (1994) Angiotensin-converting enzyme inhibitors in heart failure: new strategies justified by recent clinical trials. Int J Cardiol 43:151–163

    Article  Google Scholar 

  54. Heel RC, Brogden RN, Speight TM, Avery GS (1980) Captopril: a preliminary review of its pharmacological properties and therapeutic efficacy. Drugs 20:409–452

    Article  Google Scholar 

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Acknowledgements

The authors thank Dandan Song in the Center of Cryo-Electron Microscopy (CCEM), Zhejiang University, for their technical assistance on scanning electron microscopy, transmission electron microscopy, and Cryo-TEM. The authors thank the technical support by Bio-ultrastructure Analysis Laboratory of Analysis, Center of Agrobiology and Environmental Sciences, Zhejiang University.

Funding

This work was funded by the Educational Department Foundation of Zhejiang Province of China (N20120554).

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Contributions

Conceptualization, Chang Shu, Xinyu Zheng, and Shuli Deng; methodology, Chang Shu, Xinyu Zheng, Yang Wang, Yi Xu, and Denghui Zhang; formal analysis and investigation, Chang Shu, Yang Wang, Yi Xu, and Denghui Zhang; writing — original draft preparation, Chang Shu; writing — review and editing, Chang Shu, Xinyu Zheng, and Shuli Deng; funding acquisition, Xinyu Zheng and Shuli Deng; supervision, Shuli Deng.

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Correspondence to Shuli Deng.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Ethics Committee of Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, China (number 2018010).

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Shu, C., Zheng, X., Wang, Y. et al. Captopril inhibits matrix metalloproteinase activity and improves dentin bonding durability. Clin Oral Invest 26, 3213–3225 (2022). https://doi.org/10.1007/s00784-021-04303-x

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