Oxidative Stress and FOXO-1 Relationship in Stage III Periodontitis.

OBJECTIVES: 8-Hydroxideoxyguanosine (8-OHdG) is a marker of oxidative stress, and Forkhead Box-O1 (FOXO1) is a transcription factor and signaling integrator in cell and tissue homeostasis. This study aims to determine FOXO1 and 8-OHdG levels in serum and saliva samples of periodontitis patients and to evaluate their relationship with clinical periodontal parameters. MATERIALS AND METHODS: Twenty healthy individuals, twenty generalized Stage III Grade B periodontitis patients, and nineteen generalized Stage III Grade C periodontitis patients were included in the study. Clinical periodontal parameters (plaque index (PI), probing depth (PD), bleeding on probing (BOP), and clinical attachment level (CAL)) were recorded. Salivary and serum 8-OHdG and FOX-O1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical periodontal parameters showed a statistically significant increase in periodontitis groups compared to the control group (p < 0.05). 8-OHdG salivary levels were significantly higher in both periodontitis groups compared to the control group. The salivary FOXO1 levels were significantly lower in both periodontitis groups compared to the control group. Salivary FOXO1 level had a low-grade negative correlation with BOP and salivary 8-OHdG level. CONCLUSIONS: While reactive oxygen species increase in periodontal inflammation, low expression of FOXO1, an important transcription factor for antioxidant enzymes, supports that this molecule plays a vital role in tissue destruction, and FOXO1 can be seen as a potential immune modulator. CLINICAL RELEVANCE: The role of FOXO1 in supporting antioxidant defense may suggest that FOXO1 is a candidate target for periodontitis treatment.

Expression of tight junction proteins in smokers and non-smokers with generalized Stage III periodontitis.

OBJECTIVE: This study aims to evaluate the gingival crevicular fluid (GCF) levels of tumor necrosis factor-α (TNF-α), zonula occludens-1 (ZO-1), occludin (Occ), and tricellulin (Tric) in periodontitis, as well as their alterations due to smoking. BACKGROUND: Tight junctions (TJ), which consist of transmembrane and cytoplasmic scaffolding proteins, connect the epithelial cells of the periodontium. Occ, claudins, junctional adhesion molecules, and Tric are transmembrane TJ proteins found at the cell membrane. The transmembrane TJ proteins and the intracellular cytoskeleton are directly linked by cytoplasmic scaffolding proteins such as ZO-1. Although the functions and locations of these molecules have been defined, their behavior in periodontal inflammation is unknown. METHODS: The study included four groups: individuals with periodontal health without smoking (C; n = 31), individuals with generalized Stage III periodontitis without smoking (P; n = 28), individuals with periodontal health while smoking (CS; n = 22), and individuals with generalized Stage III periodontitis while smoking (PS; n = 18). Clinical periodontal parameters were recorded, and enzyme-linked immunosorbent assay (ELISA) was used to examine ZO-1, Occ, Tric, and TNF-α levels in GCF. RESULTS: In the periodontitis groups, clinical parameters were significantly higher (p < .001). The site-specific levels of TNF-α, ZO-1, Tric, and Occ in the P group were statistically higher than those in the other groups (p < .05). TNF-α, probing pocket depth (PPD), and bleeding on probing (BOP) exhibited positive correlations with all TJ proteins (p < .005). CONCLUSIONS: Smoking could potentially affect the levels of epithelial TJ proteins in the GCF, thereby potentially playing a significant role in the pathogenesis of the periodontal disease.

Does smoking influence tryptophan metabolism in periodontal inflammation? A cross-sectional study.

OBJECTIVES: The aim of this study was to identify the effects of smoking and periodontal inflammation on tryptophan-kynurenine metabolism as well as the correlation between these findings and clinical periodontal parameters. BACKGROUND: It has been shown that the tryptophan amino acid's primary catabolic pathway, the kynurenine pathway (KP), may serve as a key biomarker for periodontal disease. Although there are studies investigating the effect of smoking on KYN-TRP metabolism, the effect of smoking on periodontal disease through KP has not been revealed so far. METHODS: The salivary and serum samples were gathered from 24 nonsmoker (NS-P) stage III, grade B generalized periodontitis and 22 smoker (S-P) stage III, grade C generalized periodontitis patients, in addition to 24 nonsmoker (NS-C) and 24 smoker (S-C) periodontally healthy control individuals. Saliva and serum IL-6, kynurenine (KYN), and tryptophan (TRP) values, and KYN/TRP ratio were analyzed by liquid chromatography-mass spectrometry. Clinical periodontal measurements were recorded. RESULTS: Salivary TRP values were significantly higher in both periodontitis groups than control groups (p < .05). Salivary KYN values were highest in NS-P group (p < .05). Salivary KYN values did not differ significantly between periodontitis groups (p = .84). Salivary KYN/TRP ratio was significantly lower in NS-P group compared to other groups (p < .001). Serum TRP value is higher in S-P group than other groups; however, significant difference was found in S-C group (p < .05). Serum KYN values were significantly lower in smokers than nonsmokers. Serum KYN/TRP ratio is higher in NS-P group. NS-P group has the highest salivary IL-6 levels, NS-C group has the lowest values (p < .05). CONCLUSIONS: Our results point out that smoking exacerbates inflammation in the periodontium and increases TRP destruction and decreases IDO activity by suppressing KP in serum. As a result, kynurenine and its metabolites may be significant biomarkers in the link between smoking and periodontal disease.

Influence of periodontal inflammation on tryptophan-kynurenine metabolism: a cross-sectional study.

OBJECTIVES: Kynurenine pathway (KP) is the primary way of degrading tryptophan (TRP) and generates several bioactive metabolites (such as kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3OHKYN)) to regulate biological processes that include host-microbiome signaling and immune cell response. This study is aimed to determine the relationship between periodontal inflammation and tryptophan-kynurenine metabolism and identify their association with periodontal clinical parameters. MATERIALS AND METHODS: Saliva and serum samples were collected from 20 stage III, grade B generalized periodontitis patients, and 20 periodontally healthy control individuals. Samples were analyzed for IL-6, KYN, TRP, KYN/TRP ratio, KYNA, 3OHKYN, picolinic acid (PA), and quinolinic acid (QA) by liquid chromatography-mass spectrometry. Clinical periodontal parameters (plaque index (PI), probing pocket depth (PPD), gingival recession (GR), clinical attachment loss (CAL), and bleeding on probing (BOP)) were recorded. RESULTS: Clinical parameters were significantly higher in the periodontitis group (p < 0.001). Salivary IL-6, TRP, KYN, KYNA, PA, and QA levels were significantly higher and KYN/TRP ratio was significantly lower in periodontitis group than control group (p < 0.05). Serum KYN, KYN/TRP ratio and PA levels were significantly higher in periodontitis group than control group (p < 0.05). PPD, BOP, PI, and CAL had significantly positive correlations with salivary IL-6, TRP, PA, QA, and serum KYN and significantly negative correlations with salivary KYN/TRP ratio. CONCLUSIONS: Our results suggest that periodontal inflammation plays a role in local and systemic tryptophan-kynurenine metabolism. CLINICAL RELEVANCE: Due to their effects on the immune and inflammatory systems, kynurenines may be potential agents for diagnosis and treatment of periodontal diseases.

Evaluation of salivary and serum methylated arginine metabolites and nitric oxide synthase in advanced periodontitis patients.

OBJECTIVES: Methylated arginine metabolites and nitric oxide synthase (NOS) play a critical role in regulating endothelial function. The aim of this study was to determine levels of NOS, and methylated arginine metabolites (ADMA, SDMA, homoarginine, arginine, and L-NMMA) and IL-6 in serum and saliva in patients with advanced periodontal diseases and identify their association with clinical parameters. MATERIALS AND METHODS: The study consisted of two groups: healthy individuals (control: n = 24), and generalized Stage III Grade B periodontitis (P: n = 21). Clinical periodontal parameters (probing pocket depth, bleeding on probing, clinical attachment level) were recorded. IL 6 and NOS levels in saliva and serum were analyzed by enzyme-linked immunosorbent assay (ELISA). ADMA, SDMA, homoArg, arginine, and L-NMMA in saliva and serum were analyzed by liquid chromatography-mass spectrometry (LC MS/MS). RESULTS: Clinical parameters were significantly higher in the periodontitis group (p < 0.001). In periodontitis group, NOS, ADMA, and arginine levels in saliva were statistically significantly higher than control group (p < 0.05). Serum levels of SDMA were statistically significantly lower, and IL-6 was statistically significantly higher in P group than C group (p < 0.05). ADMA, NOS, and arginine levels were significantly positive correlated with all clinical periodontal parameters (p < 0.05). CONCLUSIONS: These findings suggest that there is a relationship between severity of periodontal disease and endothelial dysfunction by means of ADMA. Salivary ADMA may be related with periodontal inflammation. CLINICAL RELEVANCE: ADMA levels in periodontal inflammation are associated with endothelial dysfunction. According to the results of our study, periodontal inflammation is effective on both local and systemic methylated arginine metabolites and nitric oxide synthase levels. This may shed light on the relationship between periodontal disease and systemic status.

Endocan (ESM-1) levels in gingival crevicular fluid correlate with ICAM-1 and LFA-1 in periodontitis

Abstract: Endocan, a 50 kDa soluble proteoglycan, also called endothelial cell-specific molecule-1 (ESM-1), is involved in many major cellular activities and has been reported to be overexpressed in inflammatory conditions. This study aims to determine ESM-1 levels in gingival crevicular fluid (GCF) samples from individuals with periodontitis to determine the correlation between the levels of lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and clinical findings of periodontitis. This study enrolled 27 individuals diagnosed with Stage III-Grade C generalized periodontitis and 16 individuals as healthy controls. Bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were calculated. Enzyme-linked immunosorbent assay (ELISA) test was used for detecting the levels of ESM-1, ICAM-1, and LFA-1 in GCF samples. PPD, BOP, CAL, and GCF volumes were significantly increased in patients with periodontitis in comparison to the control group (p < 0.001). The total amount of ESM-1, ICAM-1, and LFA-1 levels in GCF were increased in the periodontitis group (p < 0.001). ESM-1 level correlated with PPD, BOP, and CAL (p < 0.05). ICAM-1 level correlated with BOP and CAL (p < 0.05). LFA-1 level correlated with PPD and CAL (p < 0.05). Our data indicate that ESM-1, ICAM-1, and LFA-1 levels are increased in GCF of patients with periodontitis. These molecules could be associated with the pathogenesis and progression of periodontal disease.

Endocan (ESM-1) levels in gingival crevicular fluid correlate with ICAM-1 and LFA-1 in periodontitis.

Endocan, a 50 kDa soluble proteoglycan, also called endothelial cell-specific molecule-1 (ESM-1), is involved in many major cellular activities and has been reported to be overexpressed in inflammatory conditions. This study aims to determine ESM-1 levels in gingival crevicular fluid (GCF) samples from individuals with periodontitis to determine the correlation between the levels of lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and clinical findings of periodontitis. This study enrolled 27 individuals diagnosed with Stage III-Grade C generalized periodontitis and 16 individuals as healthy controls. Bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were calculated. Enzyme-linked immunosorbent assay (ELISA) test was used for detecting the levels of ESM-1, ICAM-1, and LFA-1 in GCF samples. PPD, BOP, CAL, and GCF volumes were significantly increased in patients with periodontitis in comparison to the control group (p < 0.001). The total amount of ESM-1, ICAM-1, and LFA-1 levels in GCF were increased in the periodontitis group (p < 0.001). ESM-1 level correlated with PPD, BOP, and CAL (p < 0.05). ICAM-1 level correlated with BOP and CAL (p < 0.05). LFA-1 level correlated with PPD and CAL (p < 0.05). Our data indicate that ESM-1, ICAM-1, and LFA-1 levels are increased in GCF of patients with periodontitis. These molecules could be associated with the pathogenesis and progression of periodontal disease.

A disintegrin-like and metalloproteinase with thrombospondin-1 (ADAMTS-1) levels in gingival crevicular fluid correlate with vascular endothelial growth factor-A, hypoxia-inducible factor-1α, and clinical parameters in patients with advanced periodontitis.

BACKGROUND: ADAMTS (a disintegrin-like and metalloproteinase with thrombospondin) are a family of proteinases that are structurally similar to the family of matrix metalloproteinases with critical roles in damage and repair of the extracellular matrix. Their functions are closely related to inflammation, hypoxia, and vascularization. Our aim was to determine levels of ADAMTS-1 in gingival crevicular fluid (GCF) in patients with advanced periodontal diseases and identify their association with hypoxia-inducible factor-1alpha (HIF-1α), vascular endothelial growth factor (VEGF-A), and clinical parameters of periodontitis. METHODS: The study consisted of three groups: healthy individuals (control; n = 20), generalized chronic periodontitis (CP; n = 21), and generalized aggressive periodontitis (GAgP; n = 20). Clinical parameters were measured. Levels of ADAMTS-1, VEGF-A, and HIF-1α in GCF and serum were quantified by enzyme-linked immunosorbent assay (ELISA) and reported as total amounts and concentration. RESULTS: ADAMTS-1 total amount in GCF were significantly higher in patients with CP and GAgP compared with healthy individuals (P < 0.05). HIF-1α total amount in GCF were also higher in periodontitis groups compared with the control group (P < 0.05). GCF total VEGF-A content was significantly higher in the GAgP group compared with the CP and the controls (respectively; P = 0.023, P = 0.003). There was a significant correlation between ADAMTS-1, VEGF-A, and HIF-1α levels in the GCF and clinical periodontal parameters (probing depth [PD], bleeding on probing [BOP], and clinical attachment loss (CAL); P < 0.05). CONCLUSION: ADAMTS-1 may play a role in advanced periodontal disease pathogenesis in correlation with tissue hypoxia and vascularization.

Generalized Aggressive Periodontitis in a Patient With Nephrotic Syndrome Associated With Primary Renal Amyloidosis: A Case Report.

INTRODUCTION: Renal amyloidosis may lead to renal disease, and then nephrotic syndrome may develop. To the best of the authors' knowledge, this is the first case report in which a patient presents with generalized aggressive periodontitis (GAgP) and nephrotic syndrome in conjunction with renal amyloidosis. CASE PRESENTATION: An 18-year-old male presented to the periodontology department for generalized gingival recessions. He was diagnosed as having primary renal amyloidosis by his physician. The patient presented with severe gingival inflammation and alveolar bone loss. Biochemical tests were within normal limits except for serum albumin level. No amyloid deposition was found in a gingival biopsy, and the patient was diagnosed as having GAgP. Non-surgical periodontal treatment, in combination with antibiotic treatment, was performed. After 3 years, his systemic and periodontal conditions showed deterioration. CONCLUSIONS: The effects of systemic factors related to nephrotic syndrome in conjunction with renal amyloidosis and deterioration in oral hygiene may play a significant role in the progression of periodontal disease. Even if there is no amyloid deposition in periodontal tissues, clinicians should consider that nephrotic syndrome associated with systemic amyloidosis may provide an important contribution to the periodontal breakdown by the modifying conditions that affect the host response to the accumulation of dental biofilm.

Interleukin-1 and tumor necrosis factor-alpha gene polymorphisms in Turkish patients with localized aggressive periodontitis.

Localized aggressive periodontitis (LAgP) is a complex multifactorial periodontal disease to which genetic factors are thought to predispose individuals. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are potent immunomodulators and proinflammatory cytokines that have been implicated in the pathogenesis of autoimmune and infectious diseases and proposed to be risk factors for LAgP. Our aim was to investigate IL-1 alpha (+4845), IL-1 beta (+3954), and TNF-alpha (-308) gene polymorphisms in Turkish LAgP patients. We genotyped 31 LAgP patients and 31 healthy controls for IL-1alpha(+4845), IL-1beta(+3954), and TNF-alpha(-308) using standard PCR amplification followed by restriction enzyme digestion and gel electrophoresis. Higher prevalence of heterozygosity for IL-1alpha(+4845) was found in cases (65%) when compared to controls (35%) (P < 0.05). While homozygous allele 1 of IL-1beta(+3954) was the most frequent genotype in cases (62%), no controls were homozygous for this allele (P < 0.001). Homozygous allele 1 was the most common TNF-alpha genotype in both groups, however no significant difference in TNF-alpha genotypes was found between groups. In conclusion, in this Turkish population, susceptibility to LAgP is increased by heterozygosity for allele 1 of IL-1alpha(+4845) or homozygosity for allele 1 of IL-1beta(R+3954). Moreover, IL-1 gene polymorphisms appear to have a role in susceptibility to LAgP, and the above-mentioned genotypes could be an important risk factor for LAgP in the Turkish population.