Influence of alpha lipoic acid on epithelial apoptosis in experimental periodontitis

Alpha lipoic acid (ALA) is a powerful antioxidant. Its antiinflammatory effects and apoptotic mechanism have recently been studied in many diseases. This study aimed to investigate the effects of ALA on apoptotic activity in the treatment of periodontitis. Materials and methods: Thirty male Wistar rats were randomly divided into 3 groups: control (without ligature), PED (ligature + placebo, saline; oral gavage), and ALA+PED (ligature + alpha lipoic acid at 50 mg/kg/day in saline; oral gavage). Histological and biochemical analyses were performed on the mandibular first molars of sacrificed rats. Results: Biochemical myeloperoxidase activity in gingivo-mucosal tissue was measured. For immunohistochemical evaluation, tissue sections were stained with Bax, Bcl-2, proliferating cell nuclear antigen (PCNA), and 8-OHdG antibodies by streptavidin-biotin-peroxidase staining. Immunohistochemical results showed that apoptotic activity decreased in the periodontitis group. 8-OHdG reactivity increased in the ALA-administered group. Conclusion: ALA exhibited proapoptotic and antiinflammatory effects on gingivo-mucosal epithelium in the periodontitis.

Influence of alpha lipoic acid on epithelial apoptosis in experimental periodontitis

Alpha lipoic acid (ALA) is a powerful antioxidant. Its antiinflammatory effects and apoptotic mechanism have recently been studied in many diseases. This study aimed to investigate the effects of ALA on apoptotic activity in the treatment of periodontitis. Materials and methods: Thirty male Wistar rats were randomly divided into 3 groups: control (without ligature), PED (ligature + placebo, saline; oral gavage), and ALA+PED (ligature + alpha lipoic acid at 50 mg/kg/day in saline; oral gavage). Histological and biochemical analyses were performed on the mandibular first molars of sacrificed rats. Results: Biochemical myeloperoxidase activity in gingivo-mucosal tissue was measured. For immunohistochemical evaluation, tissue sections were stained with Bax, Bcl-2, proliferating cell nuclear antigen (PCNA), and 8-OHdG antibodies by streptavidin-biotin-peroxidase staining. Immunohistochemical results showed that apoptotic activity decreased in the periodontitis group. 8-OHdG reactivity increased in the ALA-administered group. Conclusion: ALA exhibited proapoptotic and antiinflammatory effects on gingivo-mucosal epithelium in the periodontitis.

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  • Chapple ILC. Role of free radicals and antioxidants in the pathogenesis of the inflammatory periodontal diseases. J Clin Pathol-Cl Mol 1996; 49: M247–M55.
  • Katsuragi H, Ohtake M, Kurasawa I, Saito K. Intracellular production and extracellular release of oxygen radicals by PMNs and oxidative stress on PMNs during phagocytosis of periodontopathic bacteria. Odontology 2003; 91: 13–8.
  • Sakallioglu U, Aliyev E, Eren Z, Aksimsek G, Keskiner I, Yavuz U. Reactive oxygen species scavenging activity during periodontal mucoperiosteal healing: An experimental study in dogs. Arch Oral Biol 2005; 50: 1040–6.
  • Koulouri O, Lappin DF, Radvar M, Kinane DF. Cell division, synthetic capacity and apoptosis in periodontal lesions analysed by in situ hybridisation and immunohistochemistry. J Clin Periodontol 1999; 26: 552–9.
  • Canakci CF, Cicek Y, Yildirim A, Sezer U, Canakci V. Increased levels of 8-hydroxydeoxyguanosine and malondialdehyde and its relationship with antioxidant enzymes in saliva of periodontitis patients. European J of Dentistry 2009; 3: 100.
  • Keleş GC, Çetinkaya BÖ, Şimşek SB, Köprülu D, Kahraman H. The role of periodontal disease on acute phase proteins in patients with coronary heart disease and diabetes. Turk J Med Sci 2007; 37: 39–44.
  • Borges I, Moreira EAM, Filho WD, de Oliveira TB, da Silva MBS, Fröde AS. Proinflammatory and oxidative stress markers in patients with periodontal disease. Mediat Inflamm 2007; 2007: 45794
  • Liles WC. Apoptosis - Role in infection and inflammation. Curr Opin Infect Dis 1997; 10: 165–70.
  • Zamzami N, Marchetti P, Castedo M, Decaudin D, Macho A, Hirsch T et al. Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell-death. J Exp Med 1995; 182: 367–77.
  • Zamzami N, Susin SA, Marchetti P, Hirsch T, GómezMonterrey I, Castedo M et al. Mitochondrial control of nuclear apoptosis. J Exp Med 1996; 183: 1533–44.
  • Lucas H, Bartold P, Dharmapatni A, Holding CA, Haynes DR. Inhibition of apoptosis in periodontitis. J Dental Research 2010; 89: 29–33.
  • Voehringer DW. BCL-2 and glutathione: alterations in cellular redox state that regulate apoptosis sensitivity. Free Radical Bio Med 1999; 27: 945–50.
  • Buttke TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunology today 1994; 15: 7.
  • Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001; 17: 888–95.
  • Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radical Bio Med 1995; 19: 227–50.
  • Wenzel U, Nickel A, Daniel H. α-lipoic acid induces apoptosis in human colon cancer cells by increasing mitochondrial respiration with a concomitant O 2 −. -generation. Apoptosis 2005; 10: 359–68.
  • Mark K, Chen JS, Steliou K, Perrine SP, Faller DV. α-Lipoic acid induces p27Kip-dependent cell cycle arrest in nontransformed cell lines and apoptosis in tumor cell lines. Am. J. Physiol 2003; 194: 325–40.
  • Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase– AKT pathway in human cancer. Nat Rev Cancer 2002; 2: 489– 50
  • Kornman KS, Page RC, Tonetti MS. The host response to the microbial challenge in periodontitis: Assembling the players. J Periodontol 2000 1997; 14: 33–53.
  • Akgul C, Moulding DA, Edwards SW. Molecular control of neutrophil apoptosis. Febs Lett 2001; 487: 318–22.
  • Murray D, Wilton J. Lipopolysaccharide from the periodontal pathogen Porphyromonas gingivalis prevents apoptosis of HL60-derived neutrophils in vitro. Infect Immun 2003; 71: 7232–5.
  • Sawa T, Nishimura F, Ohyama H, Takahashi K, Takashiba S, Murayama Y. In vitro induction of activation-induced cell death in lymphocytes from chronic periodontal lesions by exogenous Fas ligand. Infect Immun 1999; 67: 1450–4.
  • Akman S, Canakci V, Kara A, Tozoglu U, Arabaci T, Dagsuyu İM. Therapeutic effects of alpha-lipoic acid and vitamin C on alveolar bone resorption after experimental periodontitis in rats. A biochemical, histochemical and stereologic study. J Periodontol 2012: 1–10.
  • Cetinkaya BO, Keles GC, Ayas B, Sakallioglu EE, Acikgoz G. The expression of vascular endothelial growth factor in a rat model at destruction and healing stages of periodontal disease. J Periodontol 2007; 78: 1129–35.
  • Cuzzocrea S, Zingarelli B, Hake P, Salzman AL, Szabo C. Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation. Free Radical Bio Med 1998; 24: 450–9.
  • Kalkan Y, Kapakin KAT, Kara A, Atabay T, Karadeniz A, Simsek N et al. Protective effect of Panax ginseng against serum biochemical changes and apoptosis in kidney of rats treated with gentamicin sulphate. J Mol Histol 2012: 1–11.
  • Diab-Ladki R, Pellat B, Chahine R. Decrease in the total antioxidant activity of saliva in patients with periodontal diseases. Clin Oral Investig 2003; 7: 103–7.
  • Scott BC, Aruoma OI, Evans PJ, O’Neill C, Van der Vliet A, Cross CE et al. Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation. Free Radical Res 1994; 20: 119.
  • Nickander KK, McPhee BR, Low PA, Tritschler H. Alpha-lipoic acid: Antioxidant potency against lipid peroxidation of neural tissues in vitro and implications for diabetic neuropathy. Free Radical Bio Med 1996; 21: 631–9.
  • Kumar V, Abbas AK, Fausto N, Mitchell RN, editors. Robbins Basic Pathology. 8th ed. Philadelphia: Saunders Elsevier; 2007. Bilska A, Wlodek L. Lipoic acid—the drug of the future. Pharmacol Rep 2005; 57: 570–7.
  • Biewenga GP, Haenen GRMM, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol 1997; 29: 315–31.
  • McCarty MF. Versatile cytoprotective activity of lipoic acid may reflect its ability to activate signalling intermediates that trigger the heat-shock and phase II responses. Med Hypotheses 2001; 57: 313–7.
  • Bulut Ş, Uslu H, Özdemir BH, Bulut ÖE. Analysis of proliferative activity in oral gingival epithelium in immunosuppressive medication induced gingival overgrowth. Head & Face Medicine 2006; 2: 13.
  • Lucas H, Bartold PM, Dharmapatni AASSK, Holding CA, Haynes DR. Inhibition of apoptosis in periodontitis. J Dent Res 2010; 89: 29–33.
  • Xu C, Hao Y, Wei B, Ma J, Li J, Huang Q et al. Apoptotic gene expression by human periodontal ligament cells following cyclic stretch. J Periodontal Res 2011; 46: 742–8.
  • Casasco A, Casasco M, Calligaro A, Reguzzoni M, Marrone G, Romeo E. Localization of proliferating cell nuclear antigenimmunoreactivity in human dental pulp and gingiva. Bull Group Int Rech Sci Stomatol Odontol 1996; 39: 81.
  • Celenligil-Nazliel H, Ayhan A, Uzun H, Ruacan S. The effect of age on proliferating cell nuclear antigen expression in oral gingival epithelium of healthy and inflamed human gingiva. J Periodontol 2000; 71: 1567–74.
  • Kato K, Kawashiri S, Yoshizawa K, Kitahara H, Okamune A, Sugiura S et al. Expression form of p53 and PCNA at the invasive front in oral squamous cell carcinoma: correlation with clinicopathological features and prognosis. J Oral Pathol Med 2011; 40: 693–98.
  • Bates S, Vousden KH. p53 in signaling checkpoint arrest or apoptosis. Curr Opin Genet Dev 1996; 6: 12–8.
  • Özel O, Ayçiçek A, Kenar F, Aktepe F, Sargın R, Yılmaz MD et al. Histopathologic changes in the rabbit submandibular gland after 5-fluorouracil chemotherapy. Turk J Med Sci 2010; 40: 213–20.
  • Tsuji T, Mimura Y, Wen SM, Li XW, Kanekawa A, Sasaki K et al. The significance of Pcna and P53 protein in some oral tumors. Int J Oral Max Surg. 1995; 24: 221–5.
  • Irie K, Tomofuji T, Tamaki N, Sanbe T, Ekuni D, Azuma T et al. Effects of ethanol consumption on periodontal inflammation in rats. J Dent Res 2008; 87: 456–60.
  • Tarng DC, Liu TY, Huang TP. Protective effect of vitamin C on 8-hydroxy-2′-deoxyguanosine level in peripheral blood lymphocytes of chronic hemodialysis patients. Kidney Int 2004; 66: 820–31.
  • Moller P, Viscovich M, Lykkesfeldt J, Loft S, Jensen A, Poulsen HE. Vitamin C supplementation decreases oxidative DNA damage in mononuclear blood cells of smokers. Eur J Nutr 2004; 43: 267–74.
  • Dündar S, Özcura F, Meteoğlu İ, Kara ME. Effects of long-term passive smoking on the vascular endothelial growth factor and apoptosis marker expression in the retina and choroid: an experimental study. Turk J Med Sci 2012; 42: 377–83.
  • Zong WX, Li C, Hatzivassiliou G, Lindsten T, Yu QC, Yuan JY et al. Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J Cell Biol 2003; 162: 59–69.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Prediction of neurological outcome using bispectral index in patients with severe acute brain injury

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One single-tube PCR assay to detect both CD17 (A>T) and IVS-II nt-654 (C>T) homozygous mutations of β-thalassemia

Qi LIU, Jun-Li WANG, Guo-Can YANG, Xue-Jun DONG, Zong-Xin WANG, Guo-Xing GE, Xiao-Feng GU

Influence of alpha lipoic acid on epithelial apoptosis in experimental periodontitis

Adem KARA, Sümeyra AKMAN, Tevfik DEMİRCİ, Taner ARABACI

Occurrence of depression during the postpartum period and risk factors that affect the development of the depression

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Comparison of sternal intramedullary bleeding prevention strategies in cardiac surgery

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Determination of mitochondrial fragmentation and autophagosome formation in C2C12 skeletal muscle cells

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Serum leptin levels and their proportional relationship with pro- and antiinflammatory mediators in aggressive periodontitis: preliminary report

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Prevalence of type 1 diabetes mellitus in school children 6–18 years old in Diyarbakır, Southeastern Anatolian Region of Turkey

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Helicobacter pylori infection and relationship with gastric epithelial cell proliferation and apoptosis

Zühal GÜCİN, Tuğba ÇAKMAK, Nizamettin BAYYURT, Barik SALİH

The effect of chloroquine treatment in malignant astrocytomas on prognosis

Turgay BULUT, Mehmet Ali EKİCİ, Bülent TUCER, Seyit Kaan BAŞARSLAN