Research Article
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Sıçan beyninin deneysel periodontitis modelinde DDD ve KAFE uygulamasının toplam antioksidan ve toplam oksidan düzeyleri üzerine etkileri

Year 2022, Volume 6, Issue 1, 107 - 113, 27.03.2022
https://doi.org/10.30565/medalanya.1052586

Abstract

Amaç: Deneysel periodontitis modelinde kafeik asit fenetil ester (CAPE) ve/veya düşük doz doksisiklinin (LDD) beyin total antioksidan ve oksidanlar üzerine etkisinin araştırılmasıdır.

Yöntem: 48 adet erkek Wistar albino rat, kontrol grubu (C, n=8), periodontitis + CAPE grubu (PC, n=10), periodontitis + LDD (PD, n=10), periodontitis + LDD + CAPE (PCD, n=10) ve periodontitis grubu (P, n=10) şeklinde gruplara ayrıldı. Çalışma süresi 14 gün olarak belirlendi. 10µmol/kg/gün CAPE, bir intraperitoneal enjeksiyon (İP) kullanılarak,10 mg/kg/gün LDD, oral gavaj yöntemi kullanılarak uygulandı. Değişiklikler histopatolojik olarak değerlendirildi.

Bulgular: LDD ve/veya CAPE uygulamasının tüm gruplarda oksidatif stress ve alveolar kemik kaybı şiddetinin azaltması açısından faydalı sonuçlar gösterdiği belirlendi. Deney gruplarının tamamında periodontitisin kesin bulgusu olarak alveolar kemik kaybı tespit edildi. Sadece P grubunda, diğer periodontitis gruplarına kıyasla daha fazla alveoler kemik kaybı gözlenirken, PC grubunda ise en az alveolar kemik kaybı gözlendi. Gruplar arasında alveolar kemik kaybının yüksekten düşüğe sıralaması şu şekildeydi: grup P, grup PD, grup PCD, grup PC ve grup C (p < 0.05). Buna ragmen beyin gruplarına göre beyin total antioksidan durumu ve beyin total oksidan durumu ortalama değerleri arasında istatistiksel olarak anlamlı bir farklılık tespit edilmedi. (p > 0.05).

Sonuç: LDD ve CAPE kombinasyonu, tek başına veya birlikte uygulandığında oksidatif durum ve doku hasarı üzerine istatistiksel olarak herhangi bir anlamlı farklılık göstermedi. Ancak her iki ajanın da oksidatif stresi ve doku hasarlarını azaltmada faydalı etkileri vardır.

References

  • 1. Konkel JE, O'Boyle C, Krishnan S. Distal Consequences of Oral Inflammation. Front Immunol. 2019;10:1403. PMID: 31293577.
  • 2. Jepsen S, Caton JG, Albandar JM, Bissada, N. F., Bouchard, P., Cortellini, P., et al. Periodontal manifestations of systemic diseases and developmental and acquired conditions: Consensus report of workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018;89 Suppl 1:S237-48. PMID: 29926943.
  • 3. Toczewska J, Maciejczyk M, Konopka T, Zalewska A. Total Oxidant and Antioxidant Capacity of Gingival Crevicular Fluid and Saliva in Patients with Periodontitis: Review and Clinical Study. Antioxidants (Basel). 2020;9(5):450. PMID: 32456214.
  • 4. Toczewska J, Konopka T, Zalewska A, Maciejczyk M. Nitrosative Stress Biomarkers in the Non-Stimulated and Stimulated Saliva, as well as Gingival Crevicular Fluid of Patients with Periodontitis: Review and Clinical Study. Antioxidants (Basel). 2020;9(3):259 PMID: 32245286.
  • 5. Fu W, Wang H, Ren X, Yu H, Lei Y, Chen Q. Neuroprotective effect of three caffeic acid derivatives via ameliorate oxidative stress and enhance PKA/CREB signaling pathway. Behav Brain Res. 2017;328:81-6. PMID: 28411149.
  • 6. Dik B, Coskun D, Bahcivan E, Er A. Doxycycline and meloxicam can treat neuroinflammation by increasing activity of antioxidant enzymes in rat brain. Pak J Pharm Sci. 2019;32(1(Special)):391-6. PMID: 30852475.
  • 7. Yiğit U, Kırzıoğlu F, Uğuz A, Nazıroğlu M, Özmen Ö. Is caffeic acid phenethyl ester more protective than doxycycline in experimental periodontitis? Arch Oral Biol. 2017;81:61-8. PMID: 28482239.
  • 8. Basarslan SK, Osun A, Senol S, Korkmaz M, Ozkan U, Kaplan I. Protective Effects of Intralipid and Caffeic Acid Phenyl Esther (CAPE) on Neurotoxicity Induced by Ethanol in Rats. Turk Neurosurg. 2017;27(1):66-73. PMID: 27593743.
  • 9. Wei D, Zhang XL, Wang YZ, Yang CX, Chen G. Lipid peroxidation levels, total oxidant status and superoxide dismutase in serum, saliva and gingival crevicular fluid in chronic periodontitis patients before and after periodontal therapy. Aust Dent J. 2010;55(1):70-8. PMID: 20415915.
  • 10. Otan Özden F, Lütfioğlu M, Demir E, Bilgici B. Antioxidant effect of caffeic acid phenethyl ester in experimentally induced periodontitis. Clin Oral Investig. 2021;25(8):4959-66. PMID: 33770282.
  • 11. Sud'ina GF, Mirzoeva OK, Pushkareva MA, Korshunova GA, Sumbatyan NV, Varfolomeev SD. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett. 1993;329(1-2):21-4. PMID: 7689063.
  • 12. Yağan A, Kesim S, Liman N. Effect of low-dose doxycycline on serum oxidative status, gingival antioxidant levels, and alveolar bone loss in experimental periodontitis in rats. J Periodontol. 2014;85(3):478-89. PMID: 23786405
  • 13. Kuhr A, Popa-Wagner A, Schmoll H, Schwahn C, Kocher T. Observations on experimental marginal periodontitis in rats. J Periodontal Res. 2004;39(2):101-6. PMID: 15009517.
  • 14. Kazancioglu HO, Bereket MC, Ezirganli S, Aydin MS, Aksakalli S. Effects of caffeic acid phenethyl ester on wound healing in calvarial defects. Acta Odontol Scand. 2015;73(1):21-7. PMID: 25373514.
  • 15. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-11. PMID: 16214125.
  • 16. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37(2):112-9. PMID: 14725941.
  • 17. Toker H, Ozdemir H, Eren K, Ozer H, Sahin G. N-acetylcysteine, a thiol antioxidant, decreases alveolar bone loss in experimental periodontitis in rats. J Periodontol. 2009;80(4):672-8. PMID: 19335088.
  • 18. Baltacıoğlu E, Yuva P, Aydın G, Alver A, Kahraman C, Karabulut, E, et al. Lipid peroxidation levels and total oxidant/antioxidant status in serum and saliva from patients with chronic and aggressive periodontitis. Oxidative stress index: a new biomarker for periodontal disease? J Periodontol. 2014;85(10):1432-41. PMID: 24635543.
  • 19. Zhang T, Andrukhov O, Haririan H, Müller-Kern M, Liu S, Liu Z, et al. Total Antioxidant Capacity and Total Oxidant Status in Saliva of Periodontitis Patients in Relation to Bacterial Load. Front Cell Infect Microbiol. 2016;5:97. PMID: 26779448.
  • 20. Tomofuji T, Ekuni D, Irie K, Azuma T, Tamaki N, Maruyama T. et al. Relationships between periodontal inflammation, lipid peroxide and oxidative damage of multiple organs in rats. Biomed Res. 2011;32(5):343-9. PMID: 22033304.
  • 21. Akamatsu H, Asada M, Komura J, Asada Y, Niwa Y. Effect of doxycycline on the generation of reactive oxygen species: a possible mechanism of action of acne therapy with doxycycline. Acta Derm Venereol. 1992;72(3):178-179 PMID: 1357852.
  • 22. Gustaw-Rothenberg KA, Siedlak SL, Bonda DJ, Lerner A, Tabaton M, Perry G, et al. Dissociated amyloid-beta antibody levels as a serum biomarker for the progression of Alzheimer's disease: a population-based study. Exp Gerontol. 2010;45(1):47-52. PMID: 19819324.
  • 23. Bradford DW, Slubicki MN, McDuffie J, Kilbourne A, Nagi A, Williams JW Jr. Effects of Care Models to Improve General Medical Outcomes for Individuals With Serious Mental Illness. Washington (DC): Department of Veterans Affairs (US); September 2011. PMID: 23035318.
  • 24. Zafrilla P, Mulero J, Xandri JM, Santo E, Caravaca G, Morillas JM. Oxidative stress in Alzheimer patients in different stages of the disease. Curr Med Chem. 2006;13(9):1075-83. PMID: 16611085.
  • 25. Uzar E, Koyuncuoglu HR, Uz E, Yilmaz HR, Kutluhan S, Kilbas S, et al. The activities of antioxidant enzymes and the level of malondialdehyde in cerebellum of rats subjected to methotrexate: protective effect of caffeic acid phenethyl ester. Mol Cell Biochem. 2006;291(1-2):63-8. PMID: 16718360.
  • 26. Ginis Z, Ozturk G, Albayrak A, Kurt SN, Albayrak M, Fadillioglu E. Protective effects of caffeic acid phenethyl ester on ifosfamide-induced central neurotoxicity in rats. Toxicol Ind Health. 2016;32(2):337-43. PMID: 24097369.
  • 27. Huang Y, Jin M, Pi R, Zhang J, Chen M, Ouyang Y,et al. Protective effects of caffeic acid and caffeic acid phenethyl ester against acrolein-induced neurotoxicity in HT22 mouse hippocampal cells. Neurosci Lett. 2013;535:146-51. PMID: 23313590.
  • 28. Cortes AL, Gonsalez SR, Rioja LS, Oliveira S, Santos A, Prieto MC et al. Protective outcomes of low-dose doxycycline on renal function of Wistar rats subjected to acute ischemia/reperfusion injury. Biochim Biophys Acta Mol Basis Dis. 2018;1864(1):102-14. PMID: 28987762.
  • 29. Lee CZ, Yao JS, Huang Y, Zhai W, Liu W, Guglielmo BJ, et al. Dose-response effect of tetracyclines on cerebral matrix metalloproteinase-9 after vascular endothelial growth factor hyperstimulation. J Cereb Blood Flow Metab. 2006;26(9):1157-64. PMID: 16395286.
  • 30. Yan S, Myler PJ, Stuart K. Tetracycline regulated gene expression in Leishmania donovani. Mol Biochem Parasitol. 2001;112(1):61-9. PMID: 11166387.
  • 31. Ghiselli A, Serafini M, Natella F, Scaccini C. Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free Radic Biol Med. 2000;29(11):1106-14. PMID: 11121717.

Effects of LDD and CAPE administration on total antioxidant and total oxidant levels in experimental periodontitis model of rat brain

Year 2022, Volume 6, Issue 1, 107 - 113, 27.03.2022
https://doi.org/10.30565/medalanya.1052586

Abstract

Aim: Observing the effects of caffeic acid phenethyl ester (CAPE) and/or low dose doxycycline (LDD) on total antioxidant and oxidant status of brain in experimental periodontitis is the purpose of the study.

Methods: 48 male Wistar albino rats were designed as the following: control group (C, n=8), periodontitis + CAPE group (PC, n=10), periodontitis + LDD (PD, n=10), periodontitis + LDD + CAPE group (PCD, n=10), and periodontitis group (P, n=10). The time period for the experiment was 14 days. 10µmol/kg/day of CAPE was administered using an intraperitoneal injection (IP). 10 mg/kg/day of LDD was administered using an oral gavage method. Histopathological changes were evaluated.

Results: Beneficial results were seen in all of the groups after LDD and/or CAPE administration on decreasing the alveolar bone loss level and oxidative stress. All of the experimental groups showed signs of periodontitis with alveolar bone loss. The P group leads with the most alveolar bone loss compared to the other periodontitis groups and the lowest group was the PC group in the periodontitis groups. The evolution of alveolar bone loss from high to low was that group P, group PD, group PCD, group PC, and group C (P < 0.05). However, there is no statistical difference between brain total antioxidant status and brain total oxidant status average values according to brain groups (p > 0.05).

Conclusion: The combination of LDD and CAPE are not significantly different when applied alone or together on oxidative status. But both of the agents have beneficial effects on reducing the oxidative stress and tissue damages. 

References

  • 1. Konkel JE, O'Boyle C, Krishnan S. Distal Consequences of Oral Inflammation. Front Immunol. 2019;10:1403. PMID: 31293577.
  • 2. Jepsen S, Caton JG, Albandar JM, Bissada, N. F., Bouchard, P., Cortellini, P., et al. Periodontal manifestations of systemic diseases and developmental and acquired conditions: Consensus report of workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018;89 Suppl 1:S237-48. PMID: 29926943.
  • 3. Toczewska J, Maciejczyk M, Konopka T, Zalewska A. Total Oxidant and Antioxidant Capacity of Gingival Crevicular Fluid and Saliva in Patients with Periodontitis: Review and Clinical Study. Antioxidants (Basel). 2020;9(5):450. PMID: 32456214.
  • 4. Toczewska J, Konopka T, Zalewska A, Maciejczyk M. Nitrosative Stress Biomarkers in the Non-Stimulated and Stimulated Saliva, as well as Gingival Crevicular Fluid of Patients with Periodontitis: Review and Clinical Study. Antioxidants (Basel). 2020;9(3):259 PMID: 32245286.
  • 5. Fu W, Wang H, Ren X, Yu H, Lei Y, Chen Q. Neuroprotective effect of three caffeic acid derivatives via ameliorate oxidative stress and enhance PKA/CREB signaling pathway. Behav Brain Res. 2017;328:81-6. PMID: 28411149.
  • 6. Dik B, Coskun D, Bahcivan E, Er A. Doxycycline and meloxicam can treat neuroinflammation by increasing activity of antioxidant enzymes in rat brain. Pak J Pharm Sci. 2019;32(1(Special)):391-6. PMID: 30852475.
  • 7. Yiğit U, Kırzıoğlu F, Uğuz A, Nazıroğlu M, Özmen Ö. Is caffeic acid phenethyl ester more protective than doxycycline in experimental periodontitis? Arch Oral Biol. 2017;81:61-8. PMID: 28482239.
  • 8. Basarslan SK, Osun A, Senol S, Korkmaz M, Ozkan U, Kaplan I. Protective Effects of Intralipid and Caffeic Acid Phenyl Esther (CAPE) on Neurotoxicity Induced by Ethanol in Rats. Turk Neurosurg. 2017;27(1):66-73. PMID: 27593743.
  • 9. Wei D, Zhang XL, Wang YZ, Yang CX, Chen G. Lipid peroxidation levels, total oxidant status and superoxide dismutase in serum, saliva and gingival crevicular fluid in chronic periodontitis patients before and after periodontal therapy. Aust Dent J. 2010;55(1):70-8. PMID: 20415915.
  • 10. Otan Özden F, Lütfioğlu M, Demir E, Bilgici B. Antioxidant effect of caffeic acid phenethyl ester in experimentally induced periodontitis. Clin Oral Investig. 2021;25(8):4959-66. PMID: 33770282.
  • 11. Sud'ina GF, Mirzoeva OK, Pushkareva MA, Korshunova GA, Sumbatyan NV, Varfolomeev SD. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett. 1993;329(1-2):21-4. PMID: 7689063.
  • 12. Yağan A, Kesim S, Liman N. Effect of low-dose doxycycline on serum oxidative status, gingival antioxidant levels, and alveolar bone loss in experimental periodontitis in rats. J Periodontol. 2014;85(3):478-89. PMID: 23786405
  • 13. Kuhr A, Popa-Wagner A, Schmoll H, Schwahn C, Kocher T. Observations on experimental marginal periodontitis in rats. J Periodontal Res. 2004;39(2):101-6. PMID: 15009517.
  • 14. Kazancioglu HO, Bereket MC, Ezirganli S, Aydin MS, Aksakalli S. Effects of caffeic acid phenethyl ester on wound healing in calvarial defects. Acta Odontol Scand. 2015;73(1):21-7. PMID: 25373514.
  • 15. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-11. PMID: 16214125.
  • 16. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37(2):112-9. PMID: 14725941.
  • 17. Toker H, Ozdemir H, Eren K, Ozer H, Sahin G. N-acetylcysteine, a thiol antioxidant, decreases alveolar bone loss in experimental periodontitis in rats. J Periodontol. 2009;80(4):672-8. PMID: 19335088.
  • 18. Baltacıoğlu E, Yuva P, Aydın G, Alver A, Kahraman C, Karabulut, E, et al. Lipid peroxidation levels and total oxidant/antioxidant status in serum and saliva from patients with chronic and aggressive periodontitis. Oxidative stress index: a new biomarker for periodontal disease? J Periodontol. 2014;85(10):1432-41. PMID: 24635543.
  • 19. Zhang T, Andrukhov O, Haririan H, Müller-Kern M, Liu S, Liu Z, et al. Total Antioxidant Capacity and Total Oxidant Status in Saliva of Periodontitis Patients in Relation to Bacterial Load. Front Cell Infect Microbiol. 2016;5:97. PMID: 26779448.
  • 20. Tomofuji T, Ekuni D, Irie K, Azuma T, Tamaki N, Maruyama T. et al. Relationships between periodontal inflammation, lipid peroxide and oxidative damage of multiple organs in rats. Biomed Res. 2011;32(5):343-9. PMID: 22033304.
  • 21. Akamatsu H, Asada M, Komura J, Asada Y, Niwa Y. Effect of doxycycline on the generation of reactive oxygen species: a possible mechanism of action of acne therapy with doxycycline. Acta Derm Venereol. 1992;72(3):178-179 PMID: 1357852.
  • 22. Gustaw-Rothenberg KA, Siedlak SL, Bonda DJ, Lerner A, Tabaton M, Perry G, et al. Dissociated amyloid-beta antibody levels as a serum biomarker for the progression of Alzheimer's disease: a population-based study. Exp Gerontol. 2010;45(1):47-52. PMID: 19819324.
  • 23. Bradford DW, Slubicki MN, McDuffie J, Kilbourne A, Nagi A, Williams JW Jr. Effects of Care Models to Improve General Medical Outcomes for Individuals With Serious Mental Illness. Washington (DC): Department of Veterans Affairs (US); September 2011. PMID: 23035318.
  • 24. Zafrilla P, Mulero J, Xandri JM, Santo E, Caravaca G, Morillas JM. Oxidative stress in Alzheimer patients in different stages of the disease. Curr Med Chem. 2006;13(9):1075-83. PMID: 16611085.
  • 25. Uzar E, Koyuncuoglu HR, Uz E, Yilmaz HR, Kutluhan S, Kilbas S, et al. The activities of antioxidant enzymes and the level of malondialdehyde in cerebellum of rats subjected to methotrexate: protective effect of caffeic acid phenethyl ester. Mol Cell Biochem. 2006;291(1-2):63-8. PMID: 16718360.
  • 26. Ginis Z, Ozturk G, Albayrak A, Kurt SN, Albayrak M, Fadillioglu E. Protective effects of caffeic acid phenethyl ester on ifosfamide-induced central neurotoxicity in rats. Toxicol Ind Health. 2016;32(2):337-43. PMID: 24097369.
  • 27. Huang Y, Jin M, Pi R, Zhang J, Chen M, Ouyang Y,et al. Protective effects of caffeic acid and caffeic acid phenethyl ester against acrolein-induced neurotoxicity in HT22 mouse hippocampal cells. Neurosci Lett. 2013;535:146-51. PMID: 23313590.
  • 28. Cortes AL, Gonsalez SR, Rioja LS, Oliveira S, Santos A, Prieto MC et al. Protective outcomes of low-dose doxycycline on renal function of Wistar rats subjected to acute ischemia/reperfusion injury. Biochim Biophys Acta Mol Basis Dis. 2018;1864(1):102-14. PMID: 28987762.
  • 29. Lee CZ, Yao JS, Huang Y, Zhai W, Liu W, Guglielmo BJ, et al. Dose-response effect of tetracyclines on cerebral matrix metalloproteinase-9 after vascular endothelial growth factor hyperstimulation. J Cereb Blood Flow Metab. 2006;26(9):1157-64. PMID: 16395286.
  • 30. Yan S, Myler PJ, Stuart K. Tetracycline regulated gene expression in Leishmania donovani. Mol Biochem Parasitol. 2001;112(1):61-9. PMID: 11166387.
  • 31. Ghiselli A, Serafini M, Natella F, Scaccini C. Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free Radic Biol Med. 2000;29(11):1106-14. PMID: 11121717.

Details

Primary Language English
Subjects Medicine
Published Date 2022-1
Journal Section Research Article
Authors

Umut YİĞİT> (Primary Author)
USAK UNIVERSITY, FACULTY OF DENTISTRY
0000-0001-8080-2932
Türkiye


Fatma Yeşim KIRZIOĞLU>
SÜLEYMAN DEMİREL ÜNİVERSİTESİ, DİŞ HEKİMLİĞİ FAKÜLTESİ, KLİNİK BİLİMLER BÖLÜMÜ, PERİODONTOLOJİ ANABİLİM DALI
0000-0002-5240-4504
Türkiye


Özlem ÖZMEN>
MEHMET AKİF ERSOY ÜNİVERSİTESİ, VETERİNER FAKÜLTESİ
0000-0002-1835-1082
Türkiye


Abdülhadi UĞUZ This is me
BOZOK ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, BİYOFİZİK ANABİLİM DALI
0000-0002-5778-581X
Türkiye

Publication Date March 27, 2022
Submission Date January 3, 2022
Acceptance Date February 18, 2022
Published in Issue Year 2022, Volume 6, Issue 1

Cite

Vancouver Yiğit U. , Kırzıoğlu F. Y. , Özmen Ö. , Uğuz A. Effects of LDD and CAPE administration on total antioxidant and total oxidant levels in experimental periodontitis model of rat brain. Acta Medica Alanya. 2022; 6(1): 107-113.

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