Chapter 11
Role of Proteolytic Enzymes in Dental Care
P. Kalyana Chakravarthy,
Sravan Kumar Yeturu,
P. Kalyana Chakravarthy
Department of Public Health Dentistry, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, India
Search for more papers by this authorSravan Kumar Yeturu
Department of Public Health Dentistry, Amrita School of Dentistry, Amrita Vishwa Vidyapeetham, Kochi, India
Search for more papers by this authorP. Kalyana Chakravarthy,
Sravan Kumar Yeturu,
P. Kalyana Chakravarthy
Department of Public Health Dentistry, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, India
Search for more papers by this authorSravan Kumar Yeturu
Department of Public Health Dentistry, Amrita School of Dentistry, Amrita Vishwa Vidyapeetham, Kochi, India
Search for more papers by this authorBook Editor(s):Durgesh Nandini Chauhan,
Prabhu Raj Singh,
Kamal Shah,
Nagendra Singh Chauhan,
Durgesh Nandini Chauhan
Search for more papers by this authorPrabhu Raj Singh
Search for more papers by this authorKamal Shah
Search for more papers by this authorNagendra Singh Chauhan
Search for more papers by this authorSummary
Plant-based proteolytic enzymes include papain, bromelain, actinidin, and ficin. These enzymes have been tried and tested for numerous applications in the professional as well as personal oral health care. The range of applications include basic oral hygiene maintenance via dentifrices, as anti-inflammatory and adjuvant to antibiotics in postoperative management, possible role in management of cancer and oral mucositis, caries excavation, and increasing bond strength for bonding orthodontic brackets. Literature pertaining to these areas has been reviewed, and findings have been discussed with future scope for research.
References
- Jain, N., Rajwar, Y.C., Batra, M., Singh, H.P., Agarwal P., Dentistry: Turning towards Herbal Alternatives: A Review. Sch. J. App. Med. Sci., 2, 253–257, 2014.
- de Lencastre Novaes, L.C., Jozala, A.F., Lopes, A.M. et al., Stability, purification, and applications of bromelain: A review. Biotechnol. Prog., 32, 5–13, 2016.
- Tan, Y. and Li, P., Bromelain has significant clinical benefits after extraction of the third molar during chemotherapy in patients with hematologic tumor. Oncol. Lett., 15, 2962–2966, 2018.
- Inchingolo, F., Tatullo, M., Marrelli, M. et al., Clinical trial with bromelain in third molar exodontia. Eur. Rev. Med. Pharmacol. Sci., 14, 771–4, 2010.
- Majid, O.W. and Al-Mashhadani, B.A., Perioperative Bromelain Reduces Pain and Swelling and Improves Quality of Life Measures After Mandibular Third Molar Surgery: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J. Oral Maxillofac. Surg., 72, 1043–1048, 2014.
- Ghensi, P., Cucchi, A., Creminelli, L. et al., Effect of Oral Administration of Bromelain on Postoperative Discomfort After Third Molar Surgery. J. Craniofac. Surg., 28, e191–e197, 2017.
- de la Barrera-Núñez, M.-C., Yáñez-Vico, R.-M., Batista-Cruzado, A. et al., Prospective double-blind clinical trial evaluating the effectiveness of Bromelain in the third molar extraction postoperative period. Med. Oral Patol. Oral Cir. Bucal, 19, e157–62, 2014.
- Eslami, H., Yazdani, J., Khorshidi-Khiyavi, R. et al., Effect of Supplementary Administration of Anaheal on Reducing Pain, Swelling and Trismus after Mandibular Third Molar Surgery: A Splitmouth Controlled Randomized Clinical Trial. Pesqui. Bras. Odontopediatria Clin. Integr., 18, 1–9, 2018.
- Singh, T., More, V., Fatima, U. et al., Effect of proteolytic enzyme bromelain on pain and swelling after removal of third molars. J. Int. Soc. Prev. Community Dent., 6, 197, 2016.
- Ho, D., Jagdeo, J., Waldorf, H.A., Is There a Role for Arnica and Bromelain in Prevention of Post-Procedure Ecchymosis or Edema? A Systematic Review of the Literature. Dermatol. Surg., 42, 445–463, 2016.
- Ordesi, P., Pisoni, L., Nannei, P. et al., Therapeutic efficacy of bromelain in impacted third molar surgery: A randomized controlled clinical study. Quintessence Int., 45, 679–84, 2014.
- Viganò, L., Casu, C., Argentina F. F., Evaluation of the efficacy of bromelain in oral and implant surgery patients. Ital. J. Dent. Med., 2/3, 83–89, 2017.
- Shetty, V. and Mohan, A., A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Comparing the Efficacy of Systemic Enzyme Therapy for Edema Control in Orthognathic Surgery Using Ultrasound Scan to Measure Facial Swelling. J. Oral Maxillofac. Surg., 71, 1261–1267, 2013.
- Woolf, R., Snow, J., Walker, J., Broadbent, T., Resolution of an artifically induced hematoma and the influence of a proteolytic enzyme. J. Trauma, 5, 491–4, 1965.
- Gylling, U., Rintala, A., Taipale, S., Tammisto, T., The effect of a proteolytic enzyme combinate (bromelain) on the postoperative oedema by oral application A clinical and experimental study. Acta Chir. Scand., 131, 193–6, 1966.
- Maurer, H.R., Bromelain: Biochemistry, pharmacology and medical use. Cell. Mol. Life Sci., 58, 1234–1245, 2001.
- Shahid, S.K., Turakhia, N.H., Kundra, M., Shanbag, P., Daftary, Schiess W., Efficacy and Safety of Phlogenzym—A Protease Formulation, in Sepsis in Children. J. Assoc. Physicians India, 50, 527–531, 2002.
- Tinozzi, S., A., V., Effect of bromelain on serum and tissue levels of amoxicillin. Drugs Exp. Clin. Res., 4, 39–44, 1978.
- Shahid, S.K., Turakhia, N.H., Kundra, M. et al., Efficacy and safety of phlogenzym—A protease formulation, in sepsis in children. J. Assoc. Physicians India, 50, 527–31, 2002.
- Chobotova, K., Vernallis, A.B., Majid, F.A.A., Bromelain's activity and potential as an anticancer agent: Current evidence and perspectives. Cancer Lett., 290, 148–156, 2010.
- Bhui, K., Prasad, S., George, J., Shukla, Y., Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway. Cancer Lett., 282, 167–176, 2009.
- Dhandayuthapani, S., Perez, H.D., Paroulek, A. et al., Bromelain-Induced Apoptosis in GI-101A Breast Cancer Cells. J. Med. Food, 15, 344–349, 2012.
- Báez, R., Lopes, M., Salas, C., Hernández, M., In Vivo Antitumoral Activity of Stem Pineapple (Ananas comosus) Bromelain. Planta Med., 73, 1377–1383, 2007.
- Tysnes, B.B., Maurer, H.R., Porwol, T. et al., Bromelain reversibly inhibits invasive properties of glioma cells. Neoplasia, 3, 469–79, 2001.
- Mantovani, A., Allavena, P., Sica, A., Balkwill, F., Cancer-related inflammation. Nature, 454, 436–444, 2008.
- Bromelain, Comosain as a New Drug for Treating and Preventing Various Types of Cancer in the Humans—Full Text View , ClinicalTrials.gov, 2015.
- Dörr, W. and Herrmann, T., Efficacy of Wobe–Mugos® E for Reduction of Oral Mucositis after Radiotherapy. Strahlenther. Onkol., 183, 121–127, 2007.
- Gujral, M.S., Patnaik, P.M., Kaul, R. et al., Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers. Cancer Chemother. Pharmacol., 47 Suppl, S23–8, 2001.
- Kaul, R., Mishra, BK., S.P. et al., The role of Wobe–Mugos in reducing acute sequele of radiation in head and neck cancers—A clinical phase-III randomized trial. Indian J. Cancer, 36, 141–148, 1999.
-
Worthington, H., Clarkson, J., Eden, O., Interventions for preventing oral mucositis for patients with cancer receiving treatment, in: Cochrane Database Syst. Rev, H. Worthington (Ed.), p. CD000978, John Wiley & Sons, Ltd, Chichester, UK, 2006.
10.1002/14651858.CD000978.pub2 Google Scholar
- Brien, S., Lewith, G., Walker, A., Hicks, S.M., Middleton, D., Bromelain as a Treatment for Osteoarthritis: A Review of Clinical Studies. Evid. Based Complement. Alternat. Med., 1, 251– 257, 2004.
- Pavan, R., Jain, S., Shraddha, and Kumar, A., Properties and therapeutic application of bromelain: A review. Biotechnol. Res. Int., 2012, 976203, 2012.
- Jayachandran, S. and Khobre, P., Efficacy of Bromelain along with Trypsin, Rutoside Trihydrate Enzymes and Diclofenac Sodium Combination Therapy for the treatment of TMJ Osteoarthritis—A Randomised Clinical Trial. J. Clin. Diagn. Res., 11, ZC09–ZC11, 2017.
- Silva, J., Gaspar, C., Martinez-De-Oliveira, J., Palmeira-De-Oliveira, R., Palmeira-De-Oliveira, A., Antifungal activity of bromelain in Candida pre-formed biofilms , n.d.
- Brakebusch, M., Wintergerst, U., Petropoulou, T. et al., Bromelain is an accelerator of phagocytosis, respiratory burst and Killing of Candida albicans by human granulocytes and monocytes. Eur. J. Med. Res., 6, 193–200, 2001.
- Bhardwaj, A., Ballal, S., Velmurugan, N., Comparative evaluation of the antimicrobial activity of natural extracts of Morinda citrifolia, papain and aloe vera (all in gel formulation), 2% chlorhexidine gel and calcium hydroxide, against Enterococcus faecalis: An in vitro study . J. Conserv. Dent., 15, 293–7, 2012.
- Basting, R.T., Gonçalves, F.R., França, F.M.G., do Amaral, F.L.B., Flório, F.M., Antimicrobial Potential of Papain Chemomechanical Agent on Streptococcus Mutans and Lactobacillus Casei Followed by the Use of Self-Etching Adhesive Systems. J. Clin. Pediatr. Dent., 40, 62–68, 2016.
- Segura, E.P., Méndez, L., Márquez, E. et al., Effect of Carya illinoinensis, Quercus rubra and Smilax glyciphylla extracts, pectin, and papain on the dental biofilm microorganisms [Efecto de extractos de Carya illinoinensis, Quercus rubra y Smilax glyciphylla, pectina y papaina sobre los microorganis]. J. Pharm. Pharmacogn. Res., 3, 118–129, 2015.
- Mota Vde, S., Turrini, R.N.T., Poveda Vde, B., Antimicrobial activity of Eucalyptus globulus oil, xylitol and papain: A pilot study. Rev. Esc. Enferm. USP, 49, 0216–0220, 2015.
- Praveen, N.C., Rajesh, A., Madan, M. et al., In vitro Evaluation of Antibacterial Efficacy of Pineapple Extract (Bromelain) on Periodontal Pathogens. J. Int. Oral Health, 6, 96–8, 2014.
- Kulkarni, G., Rane, D.C., V., M., Comparison of the Efficacy of Chemomechanical Caries Removal (Papacarie—A Papain Gel) and Conventional Excavation in Reducing Cariogenic Flora: An. In Vivo Study . J. Int. Oral Health, 8, 564–568, 2016.
- Motta, L.J., Bussadori, S.K., Campanelli, A.P. et al., Efficacy of Papacarie(®) in reduction of residual bacteria in deciduous teeth: A randomized, controlled clinical trial. Clinics (Sao Paulo), 69, 319–22, 2014.
- Fusayama, T., Two layers of carious dentin; diagnosis and treatment. Oper. Dent., 4, 63–70, 1979.
- Murdoch-Kinch, C.A. and McLean, M.E., Minimally invasive dentistry. J. Am. Dent. Assoc., 134, 87–95, 2003.
- Beeley, J.A., Yip, H.K., Stevenson, A.G., Chemochemical caries removal: A review of the techniques and latest developments. Br. Dent. J., 188, 427–30, 2000.
- Kavvadia, K., Karagianni, V., Polychronopoulou, A., Papagiannouli, L., Primary teeth caries removal using the Carisolv chemomechanical method: A clinical trial. Pediatr. Dent., 26, 23–8, 2004.
- Ericson, D., Zimmerman, M., Raber, H. et al., Clinical Evaluation of Efficacy and Safety of a New Method for Chemo–Mechanical Removal of Caries. Caries Res., 33, 171–177, 1999.
- Ansari, Beeley, J.A., Fung, D.E., Chemomechanical caries removal in primary teeth in a group of anxious children. J. Oral Rehabil., 30, 773–9, 2003.
- Chittem, J., Sajjan, G.S., Varma, K.M., Comparative evaluation of microshear bond strength of the caries-affected dentinal surface treated with conventional method and chemomechanical method (papain). J. Conserv. Dent., 18, 369–73, 2015.
-
Sapna, K. and Pallavi, O, S, R., Efficacy of Papacarie for caries removal: An in vivo study. World J. Dent., 2, 183–6, 2011.
10.5005/jp-journals-10015-1080 Google Scholar
- Mohamed Aly Khattab, N. and Omar, O.M., Papain-based gel for chemo-mechanical caries removal: Influence on microleakage and microshear bond strength of esthetic restorative materials. J. Am. Sci., 8, 391–399, 2012.
- Hafez, M.A., Elkateb, M., El Shabrawy, S., Mahmoud, A., El Meligy, O., Microleakage Evaluation of Composite Restorations Following Papain-Based Chemo-Mechanical Caries Removal in Primary Teeth. J. Clin. Pediatr. Dent., 41, 53–61, 2017.
- AlHumaid, J., Al-Harbi, F., El Tantawi, M., Elembaby, A., X-ray microtomography assessment of Carisolv and Papacarie effect on dentin mineral density and amount of removed tissue. Acta Odontol. Scand., 76, 236–240, 2018.
- Nair, S., Nadig, R.R., Pai, V.S., Gowda, Y., Effect of a Papain-based Chemomechanical Agent on Structure of Dentin and Bond Strength: An in vitro Study. Int. J. Clin. Pediatr. Dent., 11, 161–166, 2018.
- Somani, R., Jaidka, S., Jawa, D., Mishra, S., Comparative evaluation of smear layer removal by various chemomechanical caries removal agents: An in vitro SEM study. J. Indian Soc. Pedod. Prev. Dent., 33, 204–7, 2015.
- Viral, P.M., Nagarathna, C., Shakuntala, B.S., Chemomechanical caries removal in primary molars: Evaluation of marginal leakage and shear bond strength in bonded restorations—An in vitro study. J. Clin. Pediatr. Dent., 37, 269–74, 2013.
- Bittencourt, S.T., Pereira, J.R., Rosa, A.W. et al., Mineral content removal after Papacarie application in primary teeth: A quantitative analysis. J. Clin. Pediatr. Dent., 34, 229–31, 2010.
- Kotb, R., Elkateb, M., Ahmed, A., Kawana, K., El Meligy, O., Dentin Topographic Features following Chemomechanical Caries Removal in Primary Teeth. J. Clin. Pediatr. Dent., 40, 472– 479, 2016.
- Kitsahawong, K., Seminario, A.L., Pungchanchaikul, P., Rattanacharoenthum, A., Pitiphat, W., Chemomechanical versus drilling methods for caries removal: An in vitro study . Braz. Oral Res., 29, 1–8, 2015.
- Carrillo, C.M., Tanaka, M.H., Cesar, M.F., Camargo, M.A., Juliano, Y., Novo, N.F., Use of papain gel in disabled patients. J. Dent. Child Chic. III, 75, 222–8, 2008.
- Abdul Khalek, A., Elkateb, M., Abdel Aziz, W., El Tantawi, M., Effect of Papacarie and Alternative Restorative Treatment on Pain Reaction during Caries Removal among Children: A Randomized Controlled Clinical Trial. J. Clin. Pediatr. Dent., 41, 219–224, 2017.
- Kotb, R.M.S., Abdella, A.A., El Kateb, M.A., Ahmed, A.M., Clinical evaluation of Papacarie in primary teeth. J. Clin. Pediatr. Dent., 34, 117–23, 2009.
- Alfaya, T., Cardoso Guedes, C., Fernandes, K.P. et al., Assessment of chemomechanical removal of carious lesions using Papacarie Duo™: Randomized longitudinal clinical trial. Indian J. Dent. Res., 24, 488–92, 2013.
- Motta, L.J., Bussadori, S.K., Campanelli, A.P. et al., Randomized controlled clinical trial of long-term chemo-mechanical caries removal using Papacarie™ gel. J. Appl. Oral Sci., 22, 307–13, 2014.
- Deng, Y., Feng, G., Hu, B., Kuang, Y., Song, J., Effects of Papacarie on children with dental caries in primary teeth: A systematic review and meta-analysis. Int. J. Paediatr. Dent., 28, 361–372, 2018.
- Pithon, M.M., de Souza Ferraz, C., do Couto de Oliveira, G. et al., Effect of 10% papain gel on enamel deproteinization before bonding procedure. Angle Orthod., 82, 541–545, 2012.
- Pithon, M.M., Ferraz, C.S., Oliveira, G.D.C., Dos Santos, A.M., Effect of different concentrations of papain gel on orthodontic bracket bonding. Prog. Orthod., 14, 22, 2013.
- Pithon, M.M., Campos, M.S., Coqueiro, R., da S., Effect of bromelain and papain gel on enamel deproteinisation before orthodontic bracket bonding. Aust. Orthod. J., 32, 23–30, 2016.
- Agarwal, R., Yeluri, R., Singh, C., Munshi, A., Enamel Deproteinization using Papacarie and 10% Papain Gel on Shear Bond Strength of Orthodontic Brackets Before and After Acid Etching. J. Clin. Pediatr. Dent., 39, 348–357, 2015.
- Hasija, P., Sachdev, V., Mathur, S., Rath, R., Deproteinizing Agents as an Effective Enamel Bond Enhancer—An in Vitro Study. J. Clin. Pediatr. Dent., 41, 280–283, 2017.
- Dayem, R.N. and Tameesh, M.A., A new concept in hybridization: Bromelain enzyme for deproteinizing dentin before application of adhesive system. Contemp. Clin. Dent., 4, 421–6, 2013.
- Chauhan, K., Shivanna, V., Basavanna, R., Effect of bromelain enzyme for dentin deproteinization on bond strength of adhesive system. J. Conserv. Dent., 18, 360, 2015.
- Zakarea, N.A.A., Mohamad, T.H., Taqa, A.A., Chumbley, S., Al-Juaid, S., Baho, H., A Newly Prepared Solution for the Removal of the Smear Layer. Int. J. Dent. Sci. Res., 2, 19–26, 2014.
- Yao, J.-W., Xiao, Y., Lin, F., Effect of various pH values, ionic strength, and temperature on papain hydrolysis of salivary film. Eur. J. Oral Sci., 120, 140–146, 2012.
- Mugita, N., Nambu, T., Takahashi, K., Wang, P.-L., Komasa, Y., Proteases, actinidin, papain and trypsin reduce oral biofilm on the tongue in elderly subjects and in vitro . Arch. Oral Biol., 82, 233–240, 2017.
- Nohno, K., Yamaga, T., Kaneko, N., Miyazaki, H., Tablets containing a cysteine protease, actinidine, reduce oral malodor: A crossover study. J. Breath Res., 6, 017107, 2012.
-
Yoshimatsu, D., Sugimura, S., Ioka, T.
et al., P20 Effect of protease tablet on reduction of tongue coating. Oral Dis., 11, 112–112, 2005.
10.1111/j.1601-0825.2005.01105_43.x Google Scholar
- Yoshimatsu, D., Sugimura, S., Ioka, T. et al., Reduction of Volatile Sulfur Compounds in Mouth Air by Protease Tablet. J Dent Health, 57, 22–27, 2007.
- Sugimoto, J., Takahashi, K., Komasa, Y., Effect of a protease-containing tablet with rough surface on the number of bacteria on the tongue. J. Osaka Dent. Univ., 49, 165–170, 2015.
- Kalyana, P., Shashidhar, A., Meghashyam, B., Sreevidya, K.R., Sweta, S., Stain removal efficacy of a novel dentifrice containing papain and Bromelain extracts—An in vitro study. Int. J. Dent. Hyg., 9, 229–33, 2011.
- Lyon, T.C., Parker, W.A., Barnes, G.P., Evaluation of effects of application of a citroxain-containing dentifrice. J. Esthet. Dent., 3, 51–3, 1991.
- Münchow, E.A., Hamann, H.J., Carvajal, M.T., Pinal, R., Bottino, M.C., Stain removal effect of novel papain- and bromelain-containing gels applied to enamel. Clin. Oral Investig., 20, 2315– 2320, 2016.
- Yao, J.-W., Xiao, Y., Zuo, Q. et al., Effectiveness of cysteine proteases on protein/pigment film removal. Arch. Oral Biol., 58, 1618–1626, 2013.
- Vejai Vekaash, C.J., Kumar Reddy, T.V., Venkatesh, K.V., Effect of vital bleaching with solutions containing different concentrations of hydrogen peroxide and pineapple extract as an additive on human enamel using reflectance spectrophotometer: An in vitro study . J. Conserv. Dent., 20, 337–340, 2017.
- Chakravarthy, P.K. and Acharya, S., Efficacy of extrinsic stain removal by novel dentifrice containing papain and bromelain extracts. J. Young Pharm., 4, 245–249, 2012.
- Patil, P., Ankola, A., Hebbal, M., Patil, A., Comparison of effectiveness of abrasive and enzymatic action of whitening toothpastes in removal of extrinsic stains—A clinical trial. Int. J. Dent. Hyg., 13, 25–29, 2015.
- Santos, C.L.V. and dos [UNESP], Efeito da solução de papaína na remoção do ligamento periodontal desvitalizado: estudo histomorfométrico em dentes de ratos. Aleph, 81 f.: il. + 1 CD-ROM, 2010.
- Mansfield, L.E., Ting, S., Haverly, R.W., Yoo, T.J., The incidence and clinical implications of hypersensitivity to papain in an allergic population, confirmed by blinded oral challenge. Ann. Allergy, 55, 541–3, 1985.
