The Effect of 7% Table Salt Extract on the Interleukin-6 (Il- 6) Levels Toward Wound Healing in Female Wistar Rats Induced by Staphylococcus Aureus

Turkish Journal of Physiotherapy and Rehabilitation; 32(3) ISSN 2651-4451 | e-ISSN 2651-446X

THE EFFECT OF 7% TABLE SALT EXTRACT ON THE INTERLEUKIN-6 (IL- 6) LEVELS TOWARD WOUND HEALING IN FEMALE WISTAR RATS INDUCED BY STAPHYLOCOCCUS AUREUS

Jumriani1, Prihantono2, Mardiana Ahmad3, Sitti Rafi`ah4, A. Nilawati Usman5 1Midwifery Study Program Postgraduate School, Hasanuddin University, Makassar Email : [email protected] 2 Department of Medicine Surgery, Hasanudin University Hospital Email : [email protected] 3Departement of Midwifery Postgraduate School, Hasanuddin University, Makassar Email : [email protected] 4Departement of Anatomi, Faculty of Medicine, Hasanuddin University, Makassar Email :[email protected] 5Departement of Midwifery Postgraduate School, Hasanuddin University, Makassar Email :[email protected]

ABSTRACT

Objective: This study aimed to determine the effectiveness of administering a 7 % concentration of table salt extract on Interleukin-6 (IL-6) levels in female rats (Wistar strain) induced by Staphylococcus aureus.

Methods: This research used a True Experiment Design Experiment. The research was carried out at the Microbiology Laboratory of Hasanuddin University Hospital, Makassar, in April 2021. The research sample consisted of 12 rats divided into 2 groups, 6 animals for each. The treatment with a table salt concentration of 7% was given for 7 minutes and 15 minutes, then examined the IL-6 cytokine levels by Elisa Rat R & D system method. Collecting data was using observation sheets and data analysis conducted by the Kruskal Wallis and Shapiro Wilk test.

Results: Interleukin-6 (IL-6) was a pleiotropic pro-inflammatory cytokine and a regulator of the acute phase response to antigen reagent (RA). A study showed that IL-6 had a role in the inflammatory process caused by Staphylococcus aureus bacterial infection. The mean value of IL-6 levels was 72,131 pg/ml before treatment and 65,035 pg/ml after 7% table salt extract treatment.

Conclusion: Immersion of 7% concentration of table salt for 7 minutes reduced the levels of IL-6 cytokines, about 72,131 pg/ml before immersion and 65,035 pg/ml after immersion of 7% table salt extract. Therefore, 7-minutes immersion of 7% table salt was more effective to accelerate the wound healing process in mice induced by staphylococcus aureus bacteria.

Keywords: IL-6 Cytokine Levels, 7% table salt extract, wound healing, Staphylococcus aureus

I. INTRODUCTION Salt is a chemical compound with sodium chloride as the main component and an ionic compound consisting of positive ions (cations) and negative ions (anions), thus forming neutral compounds. Salt is formed from the reaction of an acid and a base. Salt contains elements of sodium (Na) and chlorine (Cl), so it is called Sodium Chloride (NaCl), which has benefits in limiting the growth of organisms and preventing spoilage (Production, Different, and Salt 2015, Zhou et al. n.d 2016, Ii 2019). Interleukin-6 (IL-6) is a pleiotropic pro-inflammatory cytokine and is a regulator of the acute phase response to antigen reagent (RA). The role of IL-6 in biological activities, including regulation of immune response, inflammation and hematopoiesis. Interleukin-6 has an essential role in the pathogenesis of RA. A study showed that IL-6 has a role in the inflammatory process caused by Staphylococcus aureus bacterial infection (Solehati et al. 2016, Susantiningsih, 2018. Klemm Coroline.,2019) www.turkjphysiotherrehabil.org 12337

Turkish Journal of Physiotherapy and Rehabilitation; 32(3) ISSN 2651-4451 | e-ISSN 2651-446X

Staphylococcus aureus is a gram-positive bacterium, non-sporing, cocci-shaped, and arranged in clusters like grapes. Staphylococcus is a member of the normal flora of human skin and mucosa that can cause infection in humans and animals. Staphylococcus aureus can cause infections ranging from minor skin infections such as folliculitis and furunculosis. Staphylococcus usually does not cause infection in healthy skin. However, if allowed to enter the bloodstream or internal tissues, these bacteria can cause various infections. Staphylococcus aureus produces Staphylococcal enterotoxins (SE), which can cause food poisoning (Tracey A, Taylor, Chandrashekhar G, 2020).

The previous study found that the growth curve of Staphylococcus aureus at 0%, 10% and 20% NaCl in the first 0 to 3 hours did not show a difference in the number of cells in Staphylococcus aureus cultures with or without NaCl. A study conducted by Liana c Chan also discusses Staphylococcus aureus infection with the results of Priming's research improving control of Staphylococcus aureus bacterial infection. Another study revealed that 3% NaCl concentration inhibited Escherichia coli and Staphylococcus aureus bacteria growth at 37 °C. Besides, several other alternatives were also used to suppress Staphylococcus aureus bacteria, including Pagoda leaves can be used as a therapy for mastitis caused by Staphylococcus aureus infection. days of treatment with hexidine, povidone, and chlorhexidine resulted in 99.98% (p=0.0005), 90.73% (p=0.002) and 65.97% (p=0.004) a decrease in Staphylococcus aureus colonies (Ibrahim Fitri.,2018).

Previous research showed that soaking and cleaning wounds using 7% NaCl concentration reduced infection and germs in the wound, and perfect wound closure was seen, both inside and outside the wound. (Samida, 2018).

This study aimed to determine the effect of a 7% table salt concentration on IL-6 cytokine levels and wound healing.

II. MATERIALS AND METHODS Location and Research Design This research was carried out in several places. The principal place is the Microbiology Laboratory of Hasanuddin University Hospital, Makassar.

This study used experimental research that examines the effects of table salt in vivo. Therefore, the proper Experiment design was conducted by doing randomization, grouping experimental animal to be a group of 7 minutes treatment and group of 15 minutes treatment.

Population and Sample The population in this study was experimental animals, the female rats (Wistar strain) aged 4 months and bodyweight of 200 g that met the inclusion and exclusion criteria. The number of samples in this study was 12 female rats. Sample selection was carried out by purposive sampling, a sampling directly based on the criteria.

Research methods The instruments used in this study were observation sheets and Enzyme-Linked Immunosorbent Assay (ELISA) from the Bioassay Technology Laboratory to analyze levels of interleukin-6 (IL-6).

Data Analysis Analysis of interleukin-6 (IL-6) levels was using Enzyme-Linked Immunosorbent Assay (ELISA) from Bioassay Technology Laboratory. To test the effectiveness of table salt soaking time was using the Kruskal Wallis statistical test.

III. RESULT A. Laboratory Testing Phase 1. Microorganism Culture Testing

2. Chemical Analysis Test

3. Salt pH Testing

www.turkjphysiotherrehabil.org 12338

Turkish Journal of Physiotherapy and Rehabilitation; 32(3) ISSN 2651-4451 | e-ISSN 2651-446X

B. Research implementation stage: At this stage, it 80 began with an 77.325 78 adaptation of 76 experimental 74 72.131 animals, female 72 rats of the Wistar 70 68.496 strain, for 7 days. 68 After the 66 65.03 adaptation 64 process, incisions 62 were made for all 60 groups with a 58 length of 1.5 cm Pre Intervention Post Intervention and a depth of NaCl 7 minutes NaCl 15 minutes reaching the dermis layer after Staphylococcus aureus bacteria were induced. One hour after the incision, the wound was soaked. Wound immersion was divided into 2 groups consisting of groups of 7 minutes and 15 minutes. Each group consisted of 6 rats. This immersion was carried out on days 1-7 to determine immersion using 7% NaCl solution. The analysis result of wound area measurements and wound healing in 7 minutes and 15 minutes of immersion was seen in the intervention group.

C. Differences in Interleukin-6 (IL-6) Levels in the Pre and Post Intervention Groups 1. The Results Of The Measurement Of Interleukin 6 Levels In 7 Minutes And 15 Minutes Of Immersion In The Intervention Group Table 1 Differences in Interleukin-6 (IL-6) Levels in the Pre and Post Intervention Groups

Data Mean Sig. (Pg/ml) Pre Intervention NaCl 7 minutes 72.131 0.029 NaCl 15 minutes 77.325 Post Intervention NaCl 7 minutes 65.03 0.004 NaCl 15 minutes 68.496

Table 1 show that the levels of interleukin 6 before immersion in 7% NaCl 7% for 7 minutes of 72.131 pg/ml, and after immersion of 65.03 pg/ml. At the same time, the immersion of 7% NaCl for 15 minutes decreased with the value of IL 6 before soaking 77,325 pg /ml and after soaking 68,496 pg/ml. So, 7 minutes of NaCl immersion was more effective in this case and accelerated healing in rat incision wounds.

2. Comparison of IL-6 levels in NaCl immersion for 7 minutes and 15 minutes

80 77.325 78 76 74 72.131 72 70 68.496 68 66 65.03 64 62 60 58 Pre Intervention Post Intervention

NaCl 7 minutes

Figure 1 Comparison of IL-6 levels in Nacl immersion for 7 minutes and 15 minutes www.turkjphysiotherrehabil.org 12339

Turkish Journal of Physiotherapy and Rehabilitation; 32(3) ISSN 2651-4451 | e-ISSN 2651-446X

Figure 1 shows a difference in IL-6 levels before and after soaking in 7% salt for 7 minutes before soaking 72.131 pg/ml and after soaking 60,035 pg/ml. Then, the immersion for 15 minutes was 77,325 pg/m before immersion and 68,496 pg/ml after immersion. From these data, it can be seen that IL 6 levels decreased more in 7 minutes immersion compared to 15 minutes immersion. So, 7 minutes of immersion was more effective in this case, being able to accelerate wound healing in rats.

3. The Effectiveness Of NACL On Wound Healing The first week of the highest fibroblasts was in the intervention group 7 minutes. Then the lowest was in the control fibroblasts of 15 minutes immersion. In the 2nd week, each intervention and control group experienced an increase in fibroblasts and the slowest increase in the control group of 15 minutes immersion, and the highest increase was in the 7 minutes immersion group. In the 3rd week, the intervention group (7% table salt) and the control group (DTT water) continued to increase. Again, the highest number of fibroblasts was found in the intervention group, particularly 7% salt for 7 minutes immersion (Table 2).

Table 2 Changes in the number of fibroblasts

Fibroblast: 11 Fibroblast:10 Fibroblast: 14 Fibroblast:13 a. control (7 minutes) a. control (15 minutes) b. Nacl 7% (7 minutes) d. Nacl 7% (15 minutes) Histopathology Subject day 7

Fibroblast: 31 Fibroblast: 20 Fibroblast: 45 Fibroblast:37 a. control (7 minutes) b. control (15 minutes) Nacl 7% (7 minutes) d. Nacl 7% (15 minutes) Histopathology Subject day 14

Fibroblast:53 Fibroblast:50 Fibroblast:70 Fibroblast: 60 a. control (7 minutes) b. control (15 minutes) Nacl 7% (7 minutes) d. Nacl 7% (15 minutes) Histopathology Subject day 21

IV. DISCUSSION 1. Salt Definition Salt is a chemical compound whose main component is sodium chloride and an ionic compound consisting of positive ions (cations) and negative ions (anions), thus forming neutral compounds (without charge). Salt is formed from the reaction of an acid and a base. Salt contains elements of Sodium and Chlor (NaCl), so it is called Sodium Chloride (NaCl), which has benefits in limiting the growth of organisms and preventing spoilage (Production, Different, and Salt 2015, Zhou et al. n.d 2016, Ii 2019).

Salt acts as a complement to the daily household needed being a food ingredient used as a preservative and electrolyte source for the human body. High salt content results in high osmotic pressure and low water activity. In www.turkjphysiotherrehabil.org 12340

Turkish Journal of Physiotherapy and Rehabilitation; 32(3) ISSN 2651-4451 | e-ISSN 2651-446X addition, salt has bactericidal (killing power) and bacteriostatic (inhibiting power) properties, which inhibit the growth of bacteria, especially Staphylococcus aureus. In addition, salt can also accelerate wound healing because salt is also antiseptic or inhibits or slows the growth of microorganisms, even killing germs found in wounds (Li, 2017, Kammoun et al., 2019).

2. Interleukin 6 (IL-6) Interleukin-6 (IL-6) is a pleiotropic pro-inflammatory cytokine and is a regulator of the acute phase response to antigen reagent (RA). The role of IL-6 in biological activities, including regulation of immune response, inflammation and hematopoiesis. Interleukin-6 has a vital role in the pathogenesis of RA. A study showed that IL- 6 has a role in the inflammatory process caused by Staphylococcus aureus bacterial infection (Solehati et al. 2016, Susantiningsih, 2018. Klemm Coroline.,2019).

Interleukin-6 is formed by many cells and affects many targets. The primary sources of IL-6 are macrophages and lymphocytes in the area of inflammation. Interleukin-6 can also be produced by bone cells under the influence of osteotropic hormones (PTH, 1,25-dihydroxy vitamin D3) and Interleukin-1 (Winda Kusumaningrum, 2016). Increased levels of IL-6 can occur in several conditions such as sepsis, autoimmune disease, lymphoma, AIDS, alcoholic liver disease, tumour development, Alzheimer's disease, infection or post-transplant rejection process (Winda Kusumaningrum, 2016. Susangtiningsih,2018 ). Interleukin-6 is formed by many cells and affects many targets. The primary sources of IL-6 are macrophages and lymphocytes in the area of inflammation. Interleukin-6 can also be produced by bone cells under the influence of osteotropic hormones (PTH, 1,25-dihydroxy vitamin D3) and Interleukin-1 (Winda Kusumaningrum, 2016). Increased levels of IL-6 can occur in several conditions such as sepsis, autoimmune disease, lymphoma, AIDS, alcoholic liver disease, tumor development, Alzheimer's disease, infection or post-transplant rejection process (Winda Kusumaningrum, 2016. Susangtiningsih, 2018). Interleukin- 6 is a key mediator of the acute phase response. Increased levels of IL-6 can occur in several conditions such as sepsis, autoimmune diseases, lymphoma, AIDS, alcoholic liver disease, tumor development, Alzheimer's disease, infection or post-transplant rejection processes ( Susangtiningsih,2018 ).

Interleukin-6 (IL-6) plays an essential role in the T cell response to alloantigens and the formation of cytotoxic T cells. Helper T cells (T helper cells) are a sub-group of lymphocytes (white blood cell or leukocyte type) resulting from the activation of CD4+ T cells that play an essential role in the immune system. In addition, TH cells participate in activating and directing other immune cells and are essential in the immune system. T cells are formed in the bone marrow, but their proliferation and differentiation occur in the thymus gland.

1. Interleukin-7 (IL-7) plays a role in the proliferation of T and B lymphocyte progenitor cells.

2. Interleukin-8 (IL-8) functions to increase PMN adhesion to vascular endothelium. The role of cytokines (Klem, 2017).

In previous studies, IL-6 was produced rapidly in response to infection/inflammation to signal an acute phase response to the host to form an immunity. The continuous irregular synthesis of IL-6 will cause pathological effects on chronic inflammation to autoimmunity. Peritoneal fluid was used using the ELISA method to analyze the number of bacteria in mice. The median results of the levels of IL-6, IL-10, the number of bacteria in sequence were as follows: in negative control (NC) 370.530 pg/mL; 67.044pg/mL; 7.4x103cfu/m in positive control (PC) 234.556pg/mL; 42.839pg/mL; 6.8x103cfu/mL; at T1 164,019pg/mL; 17,240pg/mL; 1.1x104cfu/mL; at T2 and the conclusion of the study that VA ethanol extract is effective as a prophylactic compound that prevents bacterial invasion, especially at a dose of 40mg/200g BW rats at that dose there was a decrease in IL-6 levels and the number of bacteria (Jhonson Blair Z.,2020., Kristanti Lidwina Tri Kristanti.,2019., Tanaka Toshia.,2014).

V. CONCLUSION Treatment of a 7% concentration of the table salt extract effectively reduced Interleukin-6 (IL-6) level in the wound healing time of female rats of Wistar strain induced by Staphylococcus aureus bacteria. In addition, the 7% table salt extract for 7 minutes was more effective than salt soaking for 15 minutes in reducing Interleukin-6 (IL-6) levels in the wound healing time of female rats of Wistar strain induced by Staphylococcus aureus bacteria.

SUGGESTION

www.turkjphysiotherrehabil.org 12341

Turkish Journal of Physiotherapy and Rehabilitation; 32(3) ISSN 2651-4451 | e-ISSN 2651-446X

Further development research is expected to develop this research both in terms of method and addition of salt concentration and duration of immersion.

REFERENCES 1. Akinpelu, David A., Joseph O. Odewade, Olayinka A. Aiyegoro, Anofi O. T. Ashafa, Oluseun F. Akinpelu, and Mayowa O. Agunbiade. 2016. “Biocidal Effects of Stem Bark Extract of Chrysophyllum Albidium G . Don on Vancomycin-Resistant Staphylococcus Aureus.” BMC Complementary and Alternative Medicine 1–9. 2. Amalia, Amalia, Ratih Dewi Dwiyanti, and Haitami Haitami. 2016. “Inhibition of NaCl Against Staphylococcus Aureus Growth.” Medical Laboratory Technology Journal. 3. B. Mulyadi, Prihatini. 2016. “Clinical Pathology and Majalah Patologi. Indonesian Clinic And Medical Laboratory.” Jurnal Indonesia 21(3):261–65. 4. Balouiri, Mounyr, Moulay Sadiki, and Saad Koraichi Ibnsouda. 2016. “Methods for in Vitro Evaluating Antimicrobial Activity: A Review.” Journal of Pharmaceutical Analysis. 5. Cabezas-Pizarro, Jorge, Mauricio Redondo-Solano, Christian Umaña-Gamboa, and María Laura Arias-Echandi. 2018. “Antimicrobial Activity of Different Sodium and Potassium Salts of Carboxylic Acid against Some Common Foodborne Pathogens and Spoilage-Associated Bacteria.” Revista Argentina de Microbiologia. 6. Chen, Xu-dong Zhang Yong-gui, and Yong-feng Deng Bin Chen. 2017. “Effect of Salt Concentration on Desiccation Cracking Behavior of GMZ Bentonite.” Environmental Earth Sciences. 7. Chick, Robert Connor, Guy Travis Clifton, Kaitlin M. Peace, Brandon W. Propper, Diane F. Hale, Adnan A. Alseidi, and Timothy J. Vreeland. 2020. “Using Technology to Maintain the Education of Residents During the COVID-19 Pandemic.” Journal of Surgical Education 77(4):729–32. 8. Chrisayu, Nadia, and Eko Sulistiyono. 2016. “Ekstraksi Garam Magnesium Dari Air Laut Melalui Proses Kristalisasi.” (November):8–9. 9. Dwi Ratih. 2015. “Ritual Unik Suku Bajo Celupkan Bayi Baru Lahir Ke Dalam Laut.” 1. 10. F, Eko, Vivian V, Fouelifack Ymele F, and Mbu R. 2015. “Sitz Bath Vs Iodine Antiseptic (Betadine) Imbibed Gauze for the Management of Perineal and Vaginal Tears.” International Journal of Translation & Community Medicine 3:59–63. 11. Fleming, Paul J., and Christine Agnew-Brune. 2015. “Current Trends in the Study of Gender Norms and Health Behaviors.” Current Opinion in Psychology 5:72–77. 12. Ginting, Pricella, Hendri Faisal, Siti Fatimah Hanum, Rini Wulan Dari, Lecturer of the Faculty, Public Health, Institute of Health, Helvetia Medan, Alumni of the Faculty, Public Health, Institute of Health, And Helvetia Medan. 2020. “Test the Effectiveness of Binahong Leaf Extract Gel (Anredera Cordifolia (Ten.) Steenis) Against Healing of Cuts Infected with Staphylococcus aureus Bacteria in Rabbits ( Oryctolagus Cuniculus ) Activity Gel Of Binahong Leaf Extract ( Anredera Cordifo.” 4(3):116–25. 13. Gomes, Karina, Barros Abegão, Bruno Nascimento, Bracale Ii, Inara Guastini, Delfim Ii, Eliane Szücs, And Cecília Braga. N.D. 2018 “Effects Of Heterologous Platelet-Rich Plasma Gel On Standardized Dermal Wound Healing In Rabbits 1.” 30(3):209–15. 14. Güzel, Sevda, Yusuf Özay, Meltem Kumaş, Coşar Uzun, And Ebru Gökalp. 2019. “Biomedicine & Pharmacotherapy Wound Healing Properties , Antimicrobial And Antioxidant Activities Of Salvia Kronenburgii Rech . F . And Salvia Euphratica Montbret , Aucher & Rech . F . Var . Euphratica On Excision And Incision Wound Models In Diabetic Rat.” Biomedicine & Pharmacotherapy 111(January):1260–76. 15. Hanretty, Kevin P. 2016. Ilustrasi Obstetri. singapore: Churchill livingstone elsevier. 16. Hariani, L. (2017). Pola Proses Penyembuhan Luka sekitar melalui analisis ekspresi EGF, VEGF, TGF-beta, kolagen, MMP-1 dan pembuluha kapiler yang diinduksi adiposed derived mesenchymal stem cells pada luka primer. Surabaya: Ilmu Kedokteran Jenjang Doktor Universitas Airlangga. 17. Hartini, T. Ninuk S., R. Siwi Padmawati, Lars Lindholm, Achmad Surjono, and Anna Winkvist. 2005. “The Importance of Eating Rice: Changing Food Habits among Pregnant Indonesian Women during the Economic Crisis.” Social Science and Medicine 61(1):199–210. 18. Ii, B. A. B. 2019. “Uji Insrtument Time. Nur Indah Indri Yani , Faculty of Health Sciences, UMP,2017.” 15–30. 19. Ilmiah, Karya Tulis, Siska Sukmarani, D-III Nursing Study Program, Department of Nursing, Health Polytechnic, And the Ministry of Health. 2018 “Perineal Wounds in Postpartum Mothers 20. Indonesia, Universitas, Winda Kusumaningrum, Faculty of Medicine, Education Program, and Specialist Doctor. 2016. The Role of Interleukin 6 in Determining Output.” 21. Jabbari, Sara, John R. King, Adrian J. Koerber, and Paul Williams. 2016. “Mathematical Biology Mathematical Modelling of the Agr Operon in Staphylococcus Aureus.” 17–54. 22. Johnson, Blair Z., Andrew W. Stevenson, Cecilia M. Prêle, Mark W. Fear, and Fiona M. Wood. 2020. “The Role of IL-6 in Skin Fibrosis and Cutaneous Wound Healing.” Biomedicines. 23. Kammoun, Maroua, Thibaut Istasse, Haitham Ayeb, Neila Rassaa, Taoufik Bettaieb, and Aurore Richel. 2019. “Role of Inorganic Salts i v o r l a n o i v o L.” 24. Kementerian Kesehatan RI. 2014. “Indofatin Data and Information Center for Indonesian Independence.” Data and Information Center of the Indonesian Ministry of Health: Causes of Maternal Death 1–2. Health, Ministry. 2018. “MAIN RESULTS OF RISKESDAS 2018.” 25. Klemm, Carolin, Christin Bruchhagen, Andre Van Krüchten, Silke Niemann, Bettina Löffler, Georg Peters, Stephan Ludwig, and Christina Ehrhardt. 2017. “Mitogen-Activated Protein Kinases (MAPKs) Regulate IL-6 over-Production during Concomitant Influenza Virus and Staphylococcus Aureus Infection.” Scientific Reports. 26. Kožár, M., H. Hamilton, and J. Koščová. 2019. “Types of Wounds and the Prevalence of Bacterial Contamination of Wounds in the Clinical Practice of Small Animals.” Folia Veterinaria. 27. Linn, 2015.Cuts, In Rabbits, Department of Pharmacy, Faculty of Medicine, Health Uin, and Alauddin Makassar. “1 , 2 , 3.” 3(3):104–10. 28. Lingkungan, Jurnal Ilmu, Baigo Hamuna, Rosye H. R. Tanjung, Hendra K. Maury, Department of Science, Cenderawasih University, Department of Biology, Cenderawasih University, Department of Chemistry, Cenderawasih University, Department of Fisheries, and the University of Papua. 2018. “Study of Seawater Quality and Pollution Index Based on Physical-Chemical Parameters in the Waters of the Depapre District, Jayapura.” 16(1):35– 43. 29. Lee, Andie S., Hermínia De Lencastre, Javier Garau, Jan Kluytmans, Surbhi Malhotra-kumar, Andreas Peschel, and Stephan Harbarth. 2018. “Methicillin-Resistant Staphylococcus Aureus.” Nature Publishing Group 4(May):1–23. 30. Maryunani, A. (2015). Modern Wound Care (Modern Woundcare). Jakarta: In Media. 31. Nova Primadina dkk.2019. Wound Healing Process Seen From Cellular And Molecular Mechanism Aspects. 32. Nuraini, Sri Wahyuni, Tri Windiarto, Evi Oktavia, And Yoyo Karyono. 2015. Profile of Indonesian Population Result of SUPAS. Vol. 6. Edited By D. Handiyatmo, Parwoto, And Widaryatmo. Jakarta: Badan Pusat Statistik. 33. Nurbaity, Nurbaity. 2017. “The Role of Inorganic Salts in the Body as Basic Principles in Biochemical Treatment Systems” JRSKT - Jurnal Riset Sains Dan Kimia Terapan 1(1):21. 34. Omotoyinbo, Oluwasegun. 2016. “Effect of Varying NaCl Concentrations on the Growth Curve of Escherichia Coli and Staphylococcus Aureus.” Cell Biology.

www.turkjphysiotherrehabil.org 12342

Turkish Journal of Physiotherapy and Rehabilitation; 32(3) ISSN 2651-4451 | e-ISSN 2651-446X

35. Permadi, Wiryawan. 2018. Obstetrics and Gynecology Clinical Practice Guide Edition II. Bandung: Department of Obstetrics and Gynecology. Dr Hasan Sadikin Hospital, Faculty of Medicine, University of Padjadjaran. 36. Prastuti, Okky Putri. 2017. “The Effect of the Composition of Seawater and Sea Sand as a Source of Electrical Energy.” 1(1):35–41. 37. Prihantono, P., vbvvnvbcb Syamsu, S. A., Siagian, N. A (2020). Application Of Scaevola Taccada (Gaertn.) Roxb. Reduce Pro-Inflamatory Cytokines Interleukin-1β In Sprague Dawley Mice Suffering From Mastitis. Open Acces Macedonian Journal Of Medical Sciences, 8(A), 423-427. Http://Doi.Org/10.3889/Oamjms.2020.4363 38. Primadina, Nova, Achmad Basori, and David S. Perdanakusuma. 2019. “Wound Healing Process Seen From Cellular And Molecular Mechanism Aspects.” Qanun Medika - Medical Journal Faculty of Medicine Muhammadiyah Surabaya. 39. Production, Their Salt, Using Different, And Table Salt. 2015. “Study Of Nacl Content In Raw Water And Their Salt Production And Productivity.” 8(1):1–9. 40. Ravishankar, Kakaraparthy, Garlanka Venkata Naga Kiranmayi, Yejella Rajendra Prasad, And Lankadi Devi. 2018. “Wound Healing Activity In Rabbits And Antimicrobial Activity Of Hibiscus Hirtus Ethanolic Extract.” Brazilian Journal Of Pharmaceutical Sciences. 41. Setiawan, Lidwina Tri Kristanti, Jusak Nugraha, Pudji Lestari, Restry Sinansari, Lisa Soegianto, Wahyu Dewi Tamayanti, Luh Putu Trys Monika Handayani, And Stephanie Beatrix. 2019. “Effect Of African Leaf (Vernonia Amygdalina) To Il-6 And Il-10 Level On Staphylococcuc Aureus Infection.” Indonesian Journal Of Tropical And Infectious Disease. 42. Sh Ahmed, Afnan, Muhammad Taher, Uttam Kumar Mandal, Juliana Md Jaffri, Deny Susanti, Syed Mahmood, and Zainul Amiruddin Zakaria. 2019. “Pharmacological Properties of Centella Asiatica Hydrogel in Accelerating Wound Healing in Rabbits.” BMC Complementary and Alternative Medicine. 43. Shimekaw, Masresha, Abiye Tigabu, And Belay Tessema. 2020. “Bacterial Profile, Antimicrobial Susceptibility Pattern, And Associated Risk Factors Among Patients With Wound Infections At Debre Markos Referral Hospital, Northwest, Ethiopia.” International Journal Of Lower Extremity Wounds. 44. Sjahruddin, Armansjah Dara, Anis Irawananwar, Farida Tabri, Khairuddin Djawad, Dasril Daud, and Gemini Alam. 2015. “The Effect of Curcumin on the Acute Wound Healing of Mice.” 3(4):189–93. 45. Solehati, Tetti, Agus Rahmat, Cecep Eli Kosasih, Nur Oktavia Hidayati, Universitas Padjadjaran, 2017.“The Impact of Clean Lifestyle Health Promotion on the Attitude , Motivation , and Behaviour of Village Health Cadres. The Effect of Health Promotion on Clean and Healthy Living Behavior (PHBS) on Attitudes, Motivation, and Behavior of Health Cadres in Facul Village.” 71:310–17. 46. Studies, Programs, Medical Education, Faculty of Medicine, D. A. N. Science, Islamic University, And Syarif State. 2014. "(Eleutherine Palmifolia) In Inhibiting the Growth of Staphylococcus Aureus Bacteria." 47. Study, Program, Educator Midwife, Diploma Level, and Faculty of Health Sciences. 2017. "Perineum in Postpartum Mothers Between." 48. Suriati, Israini, Mardiana Ahmad, Nurul Aini Siagian, and Prihantono Prihantono. 2019. “The Effect Of Pagoda Leaf Extract (Clerodendrum Paniculatum L) On The IL-10 Level In Mammae Of Female Rats Strain (Sprague Dawley) Induced With Staphylococcus Aureus Bacteria.” Qanun Medika - Medical Journal Faculty of Medicine Muhammadiyah Surabaya. 49. Susantiningsih, Tiwuk, and Syazili Mustofa. 2018. “IL-6 and TNF- α Expression in Obesity.” 2:174–80. 50. Susanto, Tantut, Lantin Sulistyorini, Emi Wuri Wuryaningsih, and Syahroni Bahtiar. 2016. “School Health Promotion: A Cross-Sectional Study on Clean and Healthy Living Program Behavior (CHLB) among Islamic Boarding Schools in Indonesia.” International Journal of Nursing Sciences 3(3):291–98. 51. Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler VG.2015 Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. 52. Varble, Andrew, Sean Meaden, Rodolphe Barrangou, Edze R. Westra, A. Luciano, United Kingdom, and Nutrition Sciences. 2019. “Horizontal Gene Transfer in Staphylococci.” Nat Rev Microbiol. 53. Zhu, Manlu, and Xiongfeng Dai. 2018. “ High Salt Cross-Protects Escherichia Coli from Antibiotic Treatment through Increasing Efflux Pump Expression .” MSphere.