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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 12  |  Issue : 5  |  Page : 289-294  

Postoperative healing after surgical removal of mandibular third molar: A comparative study between two proteolytic enzymes


1 Department of Oral and Maxillofacial Surgery, Sathyabama Dental College and Hospital, Chennai, Tamil Nadu, India
2 Annamalaiyar Multispeciality Clinic, Chennai, Tamil Nadu, India
3 Department of Computer Science & Engineering, SRM Institute of Science & Technology, Chennai, Tamil Nadu, India
4 Department of Oral Pathology, Sathyabama Dental College and Hospital, Chennai, Tamil Nadu, India

Date of Submission31-Jan-2020
Date of Acceptance02-Mar-2020
Date of Web Publication28-Aug-2020

Correspondence Address:
S Tharani Kumar
Department of Oral and Maxillofacial Surgery, Sathyabama Dental College and Hospital, Old Mahabalipuram Rd, Near Sathyabama Engineering College, Semmancheri, Sithalapakkam, Chennai, Tamil Nadu.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpbs.JPBS_87_20

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   Abstract 

Objective: The postoperative symptoms after third molar removal surgery were commonly uneventful. The aim of this study was to compare two proteolytic enzymes from different origin and to prove which enzyme provides a faster healing. One of the proteolytic enzymes involves a combination with a flavonoid. This involves trypsin, bromelain, along with a flavonoid rutin. Another proteolytic enzyme is serratiopeptidase that helps in degradation of insoluble proteins causing reduced swelling in the operated site. Materials and Methods: In this study, voluntary subjects of clinically indicated bilateral lower third impaction were selected. The subjects were recommended to undergo extraction of impacted teeth in two sittings, one extraction per visit. In the first sitting, subjects were prescribed trypsin, bromelain, and rutin combination after removal of 48 teeth and in the second sitting subjects were prescribed serratiopeptidase after removal of 38 teeth. There was a time interval of 2–3 weeks in between the sittings. The post findings such as mouth opening, swelling, and pain scale were noted. Results: The results showed that the proteolytic enzyme combination of trypsin, bromelain, and rutin is better than serratiopeptidase. Conclusion: It is recommended that trypsin, bromelain, and rutin combination can be used effectively for postoperative purpose to facilitate wound healing.

Keywords: Bromelain, lyzoheal, rutin, serratiopeptidase, substance P, swelling, trypsin


How to cite this article:
Tharani Kumar S, Ashok Prasanna R, Kirubanandan JR, Elaveyini U, Prasanna Devi S, Balasubramaniam M. Postoperative healing after surgical removal of mandibular third molar: A comparative study between two proteolytic enzymes. J Pharm Bioall Sci 2020;12, Suppl S1:289-94

How to cite this URL:
Tharani Kumar S, Ashok Prasanna R, Kirubanandan JR, Elaveyini U, Prasanna Devi S, Balasubramaniam M. Postoperative healing after surgical removal of mandibular third molar: A comparative study between two proteolytic enzymes. J Pharm Bioall Sci [serial online] 2020 [cited 2020 Sep 24];12, Suppl S1:289-94. Available from: http://www.jpbsonline.org/text.asp?2020/12/5/289/292903




   Introduction Top


Postoperative symptoms after third molar removal surgery were commonly uneventful. The symptoms include swelling, redness, trismus, lymphadenopathy, fever, and masticatory problems. These symptoms may persist for a week or more depending upon the patient’s condition and postoperative care. To overcome these problems, studies have shown that using a proteolytic enzyme aids a better and faster healing[1] when compared to usual anti-inflammatory drugs.[2] In this study, a combination of proteolytic enzyme along with a flavonoid was considered. These include trypsin, bromelain, and rutin. Trypsin, which is an endopeptidase, secreted as trypsinogen in the pancreas then activated in the intestines by endokinase.[3] Bromelain is another enzyme obtained from the stems of ananas (pineapple).[4] Rutin (rutoside) a flavonoid obtained from buckwheat, asparagus, citrus fruits, and berries.[5]

Rutoside is a natural flavone derivative.

Rutin has anti-inflammatory, anti-allergy, and immunomodulatory activity.[6] The combination of these three compounds forms a natural anti-inflammatory agent. It has been observed that patients taking these enzymes showed significance reduction in pain[7] and inflammation with quicker rates of recovery.

Another proteolytic enzyme called serratiopeptidase was considered as a control group. It is derived from the nonpathogenic Enterococci bacteria Serratia E15 produced in the intestines of silkworms. This enzyme has an inflammatory effect and it is believed to induce degradation of insoluble protein products.[8] It decreases viscosity of the ooze, facilitates draining, and thus alleviates pain by preventing bradykinin release.[9] In maxillary sinus antrotomy, serratiopeptidase is said to significantly reduce buccal swelling.[10] Al-Sandook et al.[11] clinically evaluated the efficacy of orthal-forte (prolytic enzymes, trypsin and chymotrypsin) on postoperative sequel following the removal of lower impacted third molar.

The study involves comparison between trypsin, bromelain, and rutoside with another proteolytic enzyme serratiopeptidase. The aim of this study was to evaluate the effectiveness of these two enzymes and to prove that which enzyme provides a better and faster healing.


   Materials and Methods Top


The study involves by selection of 64 healthy individuals of equal sexes that fall under the following inclusion and exclusion criteria.

The inclusion criteria for selection of subjects were bilateral impacted third molar (mesioangular), subjects between the age of 16–30 years, and female subjects of either luteal or secretory phase of their menstrual periods.

The exclusion criteria involve systemic illness such as diabetes, hypertension, bleeding disorders, immunocompromised patients, pregnant and lactating women, mentally retarded, physically challenged, and uncooperative patients. All the patients were aware of the procedure and informed consent form was obtained from them. Strict instructions were given to them for proper follow-up and postoperative care. They were advised to take a preoperative X-ray (orthopantomogram [OPG]) to rule out any developmental abnormalities, temporomandibular joint problems, or bone abnormalities. The OPG also helped to ensure that the impaction is a mesioangular. Prior to the procedure, the preoperative findings were noted and are tabulated in [Table 1].
Table 1: Mean facial swelling

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First, the subjects underwent removal of 48 (right third mandibular molar) teeth under local anesthesia. The wound closure was carried out with 3-0 silk or Vicryl suture material (Ethicon Johnson and Johnson, Cincinnati, OH, USA). Saliva was collected using a collection device such as a Salivette (Nümbrecht, Germany) or equivalent before and after the impaction. The samples were stored at ≤–20°C. The substance P Elisa Kit was used to evaluate the reduction of inflammatory mediators and the results are obtained. Then the subjects were prescribed trypsin, bromelain, and rutin; subsequently, the postoperative symptoms were noted: mouth opening, pain, and infection in the operated site, lymphadenopathy, and swelling. Each of the aforementioned parameters was observed for a week. The findings were noted on alternative postoperative days 1, 3, 5, and 7. The mouth opening was measured by the interincisal distance and examined for enlargement of certain regional lymph nodes. The subjects were asked to rate pain from 0 to 10 (visual analog scale) VAS pain rating scale.[12] The swelling was examined by facial[13] symmetry and tape measuring method considering three points. Tragus is considered as a common point adjoining the angle of mouth and soft-tissue pogonion.[12] Another line adjoining from the outer canthus of the eye to the angle of the mandible bisecting the other two lines is shown in [Figure 1]. Here the tragus is considered as a common point (A). The other point (B) is considered from the intersection of tragus–angle of mouth line to the line joining outer canthus of eye and angle of the mandible. Similarly another point (C) is considered from the intersection of tragus–pogonion line to the line joining outer canthus of eye and angle of the mandible. The swelling region is considered and calculated as the overall area adjoining these three points.
Figure 1: Representation of swelling region

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Once the right side was performed completely, their findings were tabulated as given in [Table 1]. After a period of 15 days, the subjects were recalled for follow-up after satisfactory healing was achieved; the same procedure was carried out in the left side involving removal of 38 (left third mandibular molar) teeth.

It was a prospective study including patients who required removal of impacted mandibular molar tooth. This study was approved by the local institutional review board. The operation was performed by the same surgeon. In this study, descriptive and inferential statistical analyses are used wherever necessary. Results on continuous scale measurement are given as mean ± standard deviation and results on categorical scale measurement are given in percentage. Level of significance was assessed at 5%. Assumptions made for the analysis of variance test (ANOVA) were dependent variable is normally distributed and the samples were drawn at random. ANOVA was carried to rule out any significant differences in the group means between the patient groups. Student’s t test used to find significant differences of study parameters on continuous scale between two groups.

Trypsin, bromelain, and rutin

Facial swelling measurement

[Table 1] shows the mean facial swelling measurement.

Comparative table

[Table 2] compares the two treatment mean distance as calculated over a period of 7 days and [Table 3] shows the comparison of visual analog scale measurement for a sample patient.
Table 2: Comparison of means of two treatments

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Table 3: Visual analog scale measurement for a sample patient

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   Results and Discussion Top


The following inferences were made from the analysis of dataset:

  1. Lower the mean, better the treatment. Hence, treatment T1 is better than T2. The same can also be witnessed from [Table 4] and [Table 5], respectively.


  2. Covariance is used to study the consistency of the dataset. Higher the covariance, better the treatment. Hence, treatment T1 is better than T2 as seen from [Figure 2].


  3. Results of one-tailed test and two-tailed test are reported in [Table 6].


  4. It is evident from [Figure 3] that T2’s VAS is higher than T1’s VAS for all the treatment samples considered for the study, which proves that T1 is better than T2.


  5. From statistical inference of [Table 7], it is evident that there is significant difference between the treatments given to male and female patients.
Table 4: Statistical computations for treatment––T1

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Table 5: Statistical computations for treatment––T2

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Figure 2: Covariance comparisons for the two treatments

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Table 6: Statistical inferences

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Figure 3: Comparison of visual analog scale (VAS) for both the treatments

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Table 7: Test for significant difference between the treatments among different genders

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The following inferences were made from the analysis of dataset:

On oral administration, bromelain is well absorbed that in the gastrointestinal tract with maximum level in the plasma within 1h and half-life of 6–9h.

The common problems that patients complain of after the surgical removal of impacted teeth are pain, swelling, and trismus. Various measures such as application of ice, analgesics, anti-inflammatory agents, and proteolytic enzymes have been practiced to minimize these complications.[14],[15]

According to Ahmad,[16] salivary substance P is higher in inflammatory condition that can potentially impact dental pain. The salivary substance P level is more in the female patient with inflammatory condition rather than male patient. Gaspani et al.[17] showed bromelain after oral administration, the reduction in prostaglandin E2 (PGE2), and substance P concentration in the exudate. Kumakura et al.[18] showed that exudates from plasma at the inflammatory site are reduced by inhibiting the generation of bradykinin by depletion of plasma kallikrein.

The effectiveness of bromelain in reducing swelling and pain after surgical removal of third molars was assessed in Tachibana et al.[10] and it was concluded that 28 patients (70%) had reduced swelling and pain after consuming bromelain. Singh et al.[9] studied the ability of serrapeptase to decrease the postoperative swelling, trismus, and pain after third molar impaction surgery. But, our paper has compared two proteolytic enzymes[9],[10] from different origin, and to prove which enzyme provides a faster healing. One of the proteolytic enzymes involves a combination with a flavonoid. This involves trypsin, bromelain, along with a flavonoid rutin. Another proteolytic enzyme is serratiopeptidase that helps in degradation of insoluble proteins causing reduced swelling in the operated site. It is concluded that the first combination was better by 9.7% on the mean of postoperative swelling.


   Conclusion Top


Serratiopeptidase caused allergic reaction in some individuals because of proteolytic nature of the drug[19] and causes increase in eosinophils. Due to this reaction, the bronchial asthmatic patients is contraindicative for the use of the same. However, the trypsin, bromelain, and rutin combination showed better results than that of serratiopeptidase. It was revealed that the trypsin, bromelain, and rutin combination had decrease in the inflammatory mediators such as PGE2 and substance P in the oral fluid and clinically the size of the swelling, mouth opening, and exudates from the surgical site was found reduced postoperatively, thus facilitating wound healing.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Marlette RH, Amen CR An evaluation of two proteolytic enzymes and critique of the clinical study. Oral Surg Oral Med Oral Pathol 1970;29:249-54.  Back to cited text no. 1
    
2.
Pizzorno J, Murray MT The textbook of natural medicine, Seattle, WA: Bastyr University Publications; 1992.  Back to cited text no. 2
    
3.
Cederqvist K, Haglund C, Heikkilä P, Sorsa T, Tervahartiala T, Stenman UH, et al. Pulmonary trypsin-2 in the development of bronchopulmonary dysplasia in preterm infants. Pediatrics 2003;112:570-7.  Back to cited text no. 3
    
4.
Bromelain. Monograph. Altern Med Rev 2010;15:361-8.  Back to cited text no. 4
    
5.
Kreft S, Knapp M, Kreft I Extraction of rutin from buckwheat (Fagopyrum esculentumMoench) seeds and determination by capillary electrophoresis. J Agric Food Chem 1999;47:4649-52.  Back to cited text no. 5
    
6.
Rotelli AE, Guardia T, Juárez AO, Ernesto d e la Rocha N, Pelzer LE Comparative study of flavonoids in experimental models of inflammation. Pharmacol Res 2003;4:601-6.  Back to cited text no. 6
    
7.
Ustun Y, Erdogan O, Esen E, Karsli ED Comparison of the effects of 2 doses of methylprednisolone on pain, swelling and trismus after third molar surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;96:535-9.  Back to cited text no. 7
    
8.
Al-Khateeb TH, Nusair Y Effect of proteolytic enzyme serrapeptase on swelling, pain and trismus after surgical extraction of mandibular third molars. Int J Oral Maxillofac Surg 2008;37:264-8.  Back to cited text no. 8
    
9.
Singh T, More V, Fatima U, Karpe T, Aleem MA, Prameela J Effect of proteolytic enzyme bromelain on pain and swelling after removal of third molars. J Int Soc Prev Community Dent 2016;6:197-204.  Back to cited text no. 9
    
10.
Tachibana M, Mizukoshi O, Harada Y, Kawamoto K, Nakai Y A multi-centre double-blind study of serrapeptase verses placebo in post-antrotomy buccal swelling. Pharmatherapeutica 1984;3:526-30.  Back to cited text no. 10
    
11.
Al-Sandook TA, Tawfik NO, Qassim DA Clinical evaluation of the efficacy of orthal-forte (prolytic enzymes, trypsin and chymotrypsin) on postoperative sequel following the removal of lower impacted third molar. Int J Enhanc Res Sci Technol Eng 2014;3:169-73.  Back to cited text no. 11
    
12.
Gabka J, Matsumara T Measuring techniques and clinical testing of an anti-inflammatory agent (Tantum). Munch Med Wochenschr 1971;13:198.  Back to cited text no. 12
    
13.
Yusa H, Sugura M Clinical postoperative findings after removal of impacted mandibular third molar: prediction of post-operative facial swelling and pain based on pre-operative variables. Br J Oral Maxillofac Surg 2004;42:209-14.  Back to cited text no. 13
    
14.
Esen E, Taşar F, Akhan O Determination of the anti-inflammatory effects of methylprednisolone on the sequelae of third molar surgery. J Oral Maxillofac Surg 1999;57:1201-6; discussion 1206-8.  Back to cited text no. 14
    
15.
Das JR, Sreejith VP, Anooj PD, Vasudevan A Use of corticosteroids in third molar surgery: review of literature. Univ Res J Dent 2015;5:171-5.  Back to cited text no. 15
    
16.
Ahmad M, Williams J, Al-Abbousi R, Wheater M Substance P concentration in saliva of patients who report dental pain. J Adv Oral Res 2014;5:1-5.  Back to cited text no. 16
    
17.
Gaspani L, Limiroli E, Ferrario P, Bianchi M In vivo and in vitro effects of bromelain on PGE(2) and SP concentrations in the inflammatory exudate in rats. Pharmacology 2002;65:83-6.  Back to cited text no. 17
    
18.
Kumakura S, Yamashita M, Tsurufuji S Effect of bromelain on kaolin-induced inflammation in rats. Eur J Pharmacol 1988;150:295-301.  Back to cited text no. 18
    
19.
Bhagat S, Agarwal M, Roy V Serratiopeptidase: a systemic review of the existing evidence. Int J Surg 2013;11;209-17.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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