Effects of low dose doxycycline and caffeic acid phenethyl ester on sclerostin and bone morphogenic protein-2 expressions in experimental periodontitis.

We investigated the effects of caffeic acid phenethyl ester (CAPE) and low-dose doxycycline (LDD) on sclerostin and bone morphogenic protein (BMP)-2 expression in experimental periodontitis. We used male rats in groups as follows: control group (C), periodontitis + CAPE group (PC), periodontitis + LDD group (PD), periodontitis + LDD + CAPE group (PCD) and periodontitis group (P). We administered 10 µmol/kg/day CAPE by an intraperitoneal (i.p.) injection and 10 mg/kg/day LDD by oral gavage. Histopathological changes among groups were evaluated and compared. Sclerostin and BMP-2 expression was analyzed using immunohistochemistry. LDD and/or CAPE treatment ameliorated pathology. The highest sclerostin and lowest BMP-2 expressions were found in P group. Group PC exhibited the highest BMP-2 expression scores and the most significant improvement among the treatment groups. The lowest sclerostin expression was observed in the PD group. We found that preventing sclerostin activity may be a useful treatment alternative for bone resorption, especially in cases of periodontitis and peri-implantitis. We found that CAPE and/or LDD may act as anti-sclerostin agents.

Synergistic Effect of Omega-3 and Probiotic Supplementation on Preventing Ligature-Induced Periodontitis.

Omega-3 and probiotics were shown to improve periodontal health by modulating the host immune response. Recently, the combination of omega-3 and probiotics has been shown to have a potential synergistic effect on host modulation. The aim of this study was to evaluate the prophylactic role of an omega-3 and probiotic combination on alveolar bone loss (ABL) via inflammatory response in an experimental periodontitis model. Forty-three rats were divided into 5 groups as control (C, n = 8), periodontitis (P, n = 8), omega-3 + periodontitis (O, n = 8), probiotic + periodontitis (Pro, n = 10), and omega-3 + probiotic + periodontitis (OPro, n = 9). Additionally to a standardized diet, omega-3 and/or probiotics were supplemented with oral gavage to the O, Pro, and OPro groups for 44 days. Periodontitis was induced by ligature to the P, O, Pro, and OPro groups on the 30th day for 2 weeks. ABL levels were measured histopathologically, and serum interleukin (IL) 1ß, IL6, and IL10 levels were analysed by enzyme-linked immunosorbent assay. ABL increased in all periodontitis groups (P, O, Pro, and OPro), compared to C group. Compared to P group, all oral gavage groups (O, Pro, and OPro) revealed decreased ABL, which was lowest in OPro group. IL1ß and IL6 decreased and IL10 increased in OPro group, compared to P group. In conclusion, prophylactic administration of omega-3 and probiotic combination reduced ABL and improved serum IL1ß, IL6, and IL10 levels more than their single use.

Protective effects of caffeic acid phenethyl ester on the heart in experimental periodontitis against oxidative stress in rats.

BACKGROUND: Caffeic acid phenethyl ester (CAPE) may be considered as alternative treatment for periodontitis and benefit the heart by way of its ameliorative effects. OBJECTIVES: The aim of the study was to evaluate the effects of CAPE on cytokine levels and the oxidative status in the serum and heart tissue in a rat model of periodontitis. MATERIAL AND METHODS: Experimental animals were randomly assigned to 3 groups: control group (C; n = 8); periodontitis group (P; n = 10); and periodontitis + CAPE group (PC; n = 10). Caffeic acid phenethyl ester, at a dose of 10 µmol/kg/day, was administered by intraperitoneal injection over a 14-day period. Interleukin (IL)-1ß, IL­10 and tumor necrosis factor-alpha (TNF-α) were assessed in the serum. Glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were assessed in both the serum and the heart tissue homogenate. RESULTS: Increased IL­1ß, IL­10 and TNF-α serum levels were observed in the P group (p < 0.05). Caffeic acid phenethyl ester significantly decreased alveolar bone loss (ABL) and cytokine levels in the PC group (p < 0.05). Malondialdehyde, one of the strongest oxidants, was significantly decreased in the PC group as compared to the P group (p < 0.05). In both the serum and the heart tissue homogenate there were no differences in MDA levels between the PC and C groups. Furthermore, CAPE significantly increased GSH and GSH-Px levels in the serum and heart tissue (p < 0.05). CONCLUSIONS: Caffeic acid phenethyl ester has beneficial effects on the tissues affected by periodontitis.

Is the relationship between periodontitis and hyperlipidemia mediated by lipoprotein-associated inflammatory mediators?

PURPOSE: The aim of this study was to evaluate the serum levels of oxidized low-density lipoprotein (oxLDL), anti-oxLDL, and myeloperoxidase (MPO) in hyperlipidemic patients with periodontal disease. METHODS: This study included 123 patients with hyperlipidemia categorized based on metabolic control as mild to moderate (H1) (n=66) or poor (H2) (n=57), as well as systemically healthy controls (C) (n=68). Serum levels of lipids, oxLDL, anti-oxLDL, and MPO were evaluated, along with clinical periodontal parameters. RESULTS: The percentage of bleeding on probing (BOP%) and the clinical attachment level were significantly higher in the H2 group than in the C group. Patients with hyperlipidemia had a relatively high risk of developing periodontal disease. The oxLDL and anti-oxLDL levels were higher in H2 patients with periodontitis than in the control or H1 patients with periodontitis. In the H1 and H2 groups, the ratio of total cholesterol to high-density lipoprotein was significantly correlated with gingival index, BOP%, and oxLDL levels. CONCLUSIONS: Our findings indicate that the lipoprotein-associated inflammatory mediators of oxLDL, anti-oxLDL, and MPO may play an important role in the relationship between periodontal disease and hyperlipidemia.

The role of serum lipoxin A4 levels in the association between periodontal disease and metabolic syndrome.

PURPOSE: An unresolved inflammatory state contributes to the pathogenesis of periodontal disease and metabolic syndrome (MetS). Therefore, the purpose of this study was to evaluate the role of lipoxin A4 (LXA4), a proresolving lipid mediator, in the association between periodontal disease and MetS. METHODS: Sixty-seven patients with MetS and 65 patients without MetS were included in the study. Sociodemographic information was obtained via a questionnaire, and detailed medical diagnoses were made. Periodontal parameters (plaque index [PI], gingival index [GI], probing pocket depth [PD], and clinical attachment level [CAL]) and metabolic parameters were measured, and serum LXA4 levels were determined. The associations among MetS, periodontal parameters, and serum LX levels were evaluated by adjusted multivariate linear regression analyses. RESULTS: Patients with MetS were older and had a higher body mass index than patients without MetS. Periodontal parameters (PI, GI, PD, and CAL) were higher in patients with MetS than in those without MetS. Serum LXA4 levels were higher in patients without MetS. Multivariate linear regression analysis indicated a positive association between MetS and periodontal parameters (PD and CAL). Negative associations were established between MetS and LXA4 levels, and between LXA4 and periodontal parameters (PI, PD, and CAL). CONCLUSIONS: The presence of higher values of periodontal parameters in patients with MetS and the negative relationship of LXA4 with MetS and periodontal disease may support the protective role of proresolving lipid mediators in the association between periodontal disease and MetS.

Does metabolic control affect salivary adipokines in type 2 diabetes mellitus?

BACKGROUND: Adipokines produced by adipose tissue initiate pro-inflammatory events and contribute to the pathogenesis of diabetic periodontitis. OBJECTIVES: The aim of this study was to evaluate the effect of the metabolic status on the level of salivary adipokines in type 2 diabetes mellitus (T2DM) patients. MATERIAL AND METHODS: A total of 239 individuals, including 161 T2DM patients and 78 healthy (H) controls, participated in the study. The metabolic control status was evaluated in each person. Periodontal measurements were recorded. Periodontal epithelial surface area (PESA), periodontal inflamed surface area (PISA) and the total dental index (TDI) were calculated. The salivary adiponectin, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and vaspin levels were determined. RESULTS: The T2DM patients had higher periodontal parameters and adiponectin, TNF-α, IL-6, and vaspin levels as compared with the H controls (p < 0.05). As the metabolic control worsened, periodontal pocket depth (PPD) and clinical attachment level (CAL) increased. When covariates (age, gender, body mass index - BMI, education level, smoking, dental visit and tooth brushing frequency) were adjusted, only the TNF-α and vaspin levels were significantly higher in the T2DM patients (p < 0.05). In the T2DM patients, positive correlations were found between the TNF-α level and the percentage of bleeding on probing (BOP%), PPD, PESA, and PISA, and between the adiponectin level and PISA. Moreover, there was a negative relationship between the salivary volume and TDI. While the correlations IL-6-TNF-α, vaspin-triglycerides and vaspin-tooth brushing frequency were positive, the statistically significant associations vaspin-IL-6 and vaspin-low-density lipoprotein (LDL) were negative (p < 0.05). CONCLUSIONS: The severity of periodontal disease increases as the metabolic control status worsens. The levels of salivary adipokines were changed by T2DM, while being independent from the metabolic control.

Evaluation of interleukin-1ß level and oxidative status in gingival crevicular fluid during rapid maxillary expansion.

OBJECTIVES: The levels of interleukin-1ß (IL-1ß), nitric oxide (NO), total antioxidant capacity (TAC), and total oxidant status (TOS) in gingival crevicular fluid (GCF) were determined during rapid maxillary expansion (RME) treatment. MATERIALS AND METHODS: Fourteen patients (10-13 years old) were included. A modified hyrax appliance was used for the treatment. After periodontal parameters were recorded, GCF was collected from the first molars at each observation [T1:baseline:14 days after periodontal prophylaxis and instructions; T2:1 day later hyrax inserted, at passive position; T3:1 week later; after the first activation; T4:after 2 × 1/4 activation; T5:after 7 × 1/4 activation; T6:after 14 × 1/4 activation; T7:retention period on the 1 st month; and T8:retention period on the 3rd month]. RESULTS: Although the levels of IL1-ß, NO, and PD increased significantly from T1 to T2, the GI, BOP%, and PI remained unchanged throughout treatment. GCF volume at buccal and palatal surfaces increased significantly from T1 to T4, T6, T7, and T8. The parameters in GCF and TAC levels were not only higher at palatal side in comparison with buccal, but also TOS levels increased at both buccal and palatal sides. CONCLUSIONS: In this study, the differences of oxidative status and IL-1ß levels during RME treatment could be attributable to orthopedic effect of the heavy forces on maxilla and minimal orthodontic forces on teeth applied by the RME apparatus.

The role of menopause on the relationship between metabolic risk factors and periodontal disease via salivary oxidative parameters.

BACKGROUND: Periodontal disease is shown to be aggravated by an increase in the count of metabolic risk factors. This study aims to evaluate the effects of metabolic risk factors on periodontal parameters and salivary oxidative stress markers related to menopausal status. METHODS: One hundred and seventy-six women were categorized according to menopausal status, either premenopause (Pre/M) (n = 86) or postmenopause (Post/M) (n = 90). The count of metabolic risk factors was evaluated. Sociodemographics and systemic status were determined via questionnaire and medical records. After clinical periodontal measurements and saliva collection, myeloperoxidase (MPO), total oxidant status (TOS) and total antioxidant capacity (TAOC) were determined by enzyme-linked immunosorbent assay and automatic colorimetric method. Oxidative stress index (OSI) was also calculated. RESULTS: The count of metabolic risk factors was higher in the Post/M group than the Pre/M group. Periodontal parameters and TOS levels were elevated by an increase in the count of metabolic risk factors. Multivariate regression analyses revealed that periodontal (clinical attachment level and missed teeth) and oxidative (MPO and OSI) parameters increased and TAOC levels decreased due to menopause. Additionally, positive relationships between periodontal and oxidative parameters were determined. CONCLUSION: These findings suggest that salivary oxidative stress level may be an indicator of worsened periodontal status related to menopause and the count of metabolic risk factors.

The effect of menopause on the relationship between hyperlipidemia and periodontal disease via salivary 8-hydroxy-2'-deoxyguanosine and myeloperoxidase levels.

OBJECTIVE: Impairment of the lipid metabolism could affect the periodontal disease; increased oxidative stress may have a role in this relationship. The aim of the present study was to evaluate the role of menopause in the relationship between hyperlipidemia and periodontal disease via oxidative stress markers in saliva. MATERIALS AND METHODS: Sixty-seven women were enrolled in the study and divided into four groups as systemically healthy and premenopause (C) (n = 18), hyperlipidemia and premenopause (H) (n = 16), systemically healthy and postmenopause (M) (n = 17), and hyperlipidemia and postmenopause (MH) (n = 16). Sociodemographics, periodontal and metabolic parameters, and saliva oxidative markers (myeloperoxidase [MPO] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) were evaluated. RESULTS: Menopause and/or hyperlipidemia were associated with an increase in all evaluated periodontal parameters. Saliva 8-OHdG and MPO levels were higher in menopausal groups (M and MH). Multivariate linear regression analyses revealed that hyperlipidemia was related to an increase in periodontal parameters. Salivary oxidative stress markers and periodontal parameters were also positively associated with menopause and hyperlipidemia. CONCLUSION: Saliva 8-OHdG and MPO levels may indicate that the relationship between periodontal disease and hyperlipidemia is aggravated by menopause.

Is caffeic acid phenethyl ester more protective than doxycycline in experimental periodontitis?

BACKGROUND AND OBJECTIVES: Host modulation therapies (anti-inflammatory drugs, bone-stimulating agents, anti-proteinase etc.) target the inhibition or stabilization of tissue breakdown. The aim of the present study was to evaluate the effects of caffeic acid phenethyl ester (CAPE) and/or low dose doxycycline (LDD) administrations on alveolar bone loss (ABL), serum cytokines and gingival apoptosis, as well as the levels of oxidants and anti-oxidants in rats with ligature-induced periodontitis. MATERIAL AND METHODS: The animals were randomly divided into five groups: Group C (periodontally healthy), Group PC (Periodontitis+CAPE), Group PD (Periodontitis+LDD), Group PCD (Periodontitis+CAPE+LDD), Group P (Periodontitis). Experimental periodontitis was induced for 14days. Levels of ABL, and the serum cytokines, interleukin (IL)-1 ß, IL-6, tumor necrosis factor-α (TNF-α) and IL-10 were assessed as were the levels of the oxidants and anti-oxidants, malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GSH-Px), and levels of gingival apoptosis. RESULTS: The lowest ABL levels was evident in the PC group, among the experimental groups. There was also less inflammatory infiltration in the PC group than the PD group. IL-1ß, IL-6, and IL-10 were lower in the PC group and higher in the P group in comparison to the levels in the other experiment groups. TNF-α levels in the PD group were higher than levels in the PC and PCD groups. The PC and PCD groups did not differ from the C group in regard to MDA levels. The highest GSH-Px level was found in the PC group. Gingival apoptosis in the PC group was not only lower than the PD and PCD groups, but also lower than in the C group. CONCLUSION: The present study suggests that CAPE has more anti-inflammatory, anti-oxidant and anti-apoptotic effects than LDD, with no additive benefits of a CAPE+LDD combination being evident in rats with periodontitis.

Is a Cholestrol-Enriched Diet a Risk Factor for Alveolar Bone Loss?

BACKGROUND: This study aims to investigate the effects of a 2% cholesterol-enriched diet on alveolar bone loss (ABL) and serum levels of pro-oxidants and antioxidant enzymes in rats with experimental periodontitis. METHODS: Rats were randomized into the four groups: 1) group C (standard diet/periodontally healthy); 2) group Hc (high-cholesterol diet); 3) group HcP (high-cholesterol diet/periodontitis); and 4) group P (standard diet/periodontitis). All rats were fed for 8 weeks. At 6 weeks, experimental periodontitis was induced. At the end of week 8, the rats were sacrificed. Histomorphometric and histopathologic analyses were performed. Malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase, and glutathione peroxidase (GPX) levels in serum were measured with enzyme-linked immunosorbent assay. RESULTS: Experimental groups exhibited increases in: 1) total cholesterol, 2) low-density lipoprotein, and 3) high-density lipoprotein compared to group C. The cholesterol-enriched diet induced ABL in group Hc; groups HcP and P had more extensive ABL. The most polymorphonuclear leukocyte infiltration in periodontal tissues was found in group HcP. MDA levels were higher in all experimental groups than in group C, but significant in the HcP group. A high-cholesterol diet, with or without periodontitis, resulted in more decreases in GPX and more increases in NO compared to group P. CONCLUSION: Although any additive effect of cholesterol-enriched diet to ABL was not found in rats with ligature-induced experimental periodontitis, these findings revealed that a cholesterol-enriched diet could lead to ABL and an increase in periodontal inflammation and serum pro-oxidants.

Serum Lp-PLA2: as a novel viewpoint in periodontal treatment of hyperlipidaemics.

BACKGROUND/AIM: To evaluate the effects of periodontal treatment on serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and C-reactive protein (CRP) levels in hyperlipidaemic patients with periodontitis. MATERIALS AND METHODS: The study included 52 hyperlipidaemics and 28 systemically healthy controls (C) with periodontitis. Of the 52 hyperlipidaemics, 29 received a suggested diet (HD), and 23 of them were prescribed statin (HS). Clinical periodontal parameters, serum lipids, Lp-PLA2, and CRP levels were assessed at the baseline and 2 months after the completion of the nonsurgical periodontal treatment (2MPT). Serum parameters were also evaluated 1 week following the periodontal treatment (1WPT). RESULTS: At the baseline, patients in the HS group had a higher percentage of bleeding on probing than those in the C and HD groups. Hyperlipidaemics had higher serum triglyceride levels than the control group at 2MPT compared to the baseline. At 2MPT, the levels of Lp-PLA2 in the HS group were significantly higher compared to the baseline and 1WPT. There were no statistically significant differences in CRP levels between study periods for all groups. CONCLUSION: The periodontal treatment may affect the inflammatory control of hyperlipidaemic patients with periodontitis via increased Lp-PLA2 levels and severity of the impaired lipid metabolism. These findings may be important regarding the therapeutic strategies for hyperlipidaemics with periodontitis.

Lipoxin A4 and Neutrophil/Lymphocyte Ratio: A Possible Indicator in Achieved Systemic Risk Factors for Periodontitis.

BACKGROUND: The aim of this study was to evaluate the serum lipoxin A4 (LXA4) and neutrophil/lymphocyte (Ne/Ly) ratio in individuals with achieved systemic risk factors for periodontitis. MATERIAL AND METHODS: One hundred and eighty volunteers (69 male, 111 female) who were categorized as systemically healthy control, diabetes, hyperlipidemia, obese and menopause were recruited for this cross-sectional study. Sociodemographic characteristics and oral health behaviors were recorded via questionnaire. Clinical periodontal parameters, including plaque index (PI), gingival index (GI), probing pocket depth (PD), clinical attachment level (CAL), sulcus bleeding index (SBI) and decayed, missing, and filled teeth index (DMFT), were assessed. Systemic parameters and LXA4 levels were evaluated in serum samples. RESULTS: Clinical periodontal parameters and DMFT were higher in subjects with achieved systemic risk factors than in healthy subjects. The systemically healthy with periodontitis group had higher serum LXA4 levels than the systemically healthy with non-periodontitis group (P<0.05). The Ne/Ly ratio was higher in the hyperlipidemic group with periodontitis than in the hyperlipidemic group with non-periodontitis (P<0.05). In the control group, serum LXA4 levels were positively correlated with the PD, CAL and SBI. CONCLUSIONS: In the presence of periodontitis, an increase in LXA4 levels and the Ne/Ly ratio in hyperlipidemic patients could contribute to the hypothesis that these parameters could be an indicator in periodontitis and its systemic risk factors.

Ghrelin levels in chronic periodontitis patients.

Ghrelin is a peptide hormone that has modulatory effects on the immune system. This study was designed to evaluate plasma ghrelin levels in patients with chronic periodontitis and to investigate if a relationship exists between ghrelin and periodontal parameters, serum cytokines, and bone turnover markers. Thirty-five chronic periodontitis patients (CP) and periodontal healthy individuals (C) were included in this study. Periodontal parameters were recorded. Blood samples were obtained to determine the levels of total and acylated ghrelin, interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), the soluble receptor activator nuclear factor kappaB ligand (sRANKL), alkaline phosphatase (ALP), and osteocalcin (OSC). Plasma levels of total and acylated ghrelin were significantly elevated in the CP group compared with the C group (p < 0.05). The difference was significant only between males in the two groups (groups were compared with respect to gender) (p < 0.05). There was no difference between the groups regarding the levels of serum sRANKL, TNF-α, and ALP. A relative increase in the serum levels of IL-1ß and a decrease in the serum levels of OSC of the CP group were observed (p < 0.05). In addition, positive correlations between total ghrelin/ALP and total ghrelin/acylated ghrelin were discovered. We found no direct correlation between ghrelin levels and periodontal parameters. Our results indicate an increase of total and acylated ghrelin levels in patients with chronic periodontitis. Further, studies in larger populations (which could include ghrelin levels in gingival tissue, gingival crevicular fluid, and saliva) are needed in order to confirm the role of ghrelin in periodontal disease.

The gingival crevicular fluid levels of interleukin-11 and interleukin-17 in patients with aggressive periodontitis.

BACKGROUND: The balance (ratio) of anti-inflammatory and proinflammatory cytokines is thought to play an important role in the pathogenesis of chronic periodontitis. Moreover, the imbalance of anti-inflammatory/proinflammatory cytokines may modulate disease progression in aggressive periodontitis (AgP). This study aims to investigate the levels of interleukin (IL)-11 and IL-17 and their ratio in gingival crevicular fluid (GCF) in patients with AgP. METHODS: This study included 20 patients with generalized AgP (GAgP) and 18 healthy controls (HC). For each patient, the values of clinical parameters, such as gingival index, plaque index, probing depth, and clinical attachment level, were recorded. Levels of IL-11 and IL-17 in GCF samples were evaluated using enzyme-linked immunosorbent assay. The values of clinical parameters, cytokine levels, and the ratios of cytokines were evaluated. RESULTS: The values of all the clinical parameters were significantly higher in the GAgP group than in the HC group (P < 0.001). The total amount and concentration of IL-11 and the concentration of the IL-17 and IL-11/IL-17 ratio were significantly lower in the GAgP group than in the HC group (P < 0.001). The total amount of IL-17 was not significantly different between the groups (P = 0.317). CONCLUSIONS: The IL-11/IL-17 ratio was decreased in the GAgP group because of the decreased IL-11 levels. The IL-11/IL-17 axis and the link between IL-17 and neutrophil function disorders in AgP should be investigated to clarify the role of the IL-11/IL-17 axis and its balance and imbalance in the pathogenesis of AgP.

The investigation of gingival iron accumulation in thalassemia major patients.

BACKGROUND: Thalassemia major (TM) is an autosomal-recessive genetic blood disorder. Regular blood transfusions to improve chronic anemia caused by ineffective erythropoiesis and hemolysis lead to iron overload in many organs in TM patients. The aim of this study was to investigate the periodontal status and the iron accumulation in gingival tissues of TM patients and assess whether iron deposition in gingival biopsies could be an alternative method for the diagnosis of body iron overload in TM patients. MATERIALS AND METHODS: This study was conducted on 22 TM patients and 20 healthy matched controls. Plaque index, gingival index, and probing pocket depth were measured and gingival biopsies were obtained in all subjects. Venous blood samplings and liver biopsies were carried out only in patients with thalassemia. Gingiva and liver tissue samples were evaluated histopathologically for inflammation, iron accumulation, and fibrosis. RESULTS: There was no difference between the groups regarding periodontal health, and all patients had mild gingivitis. Gingival iron accumulation was observed only in the TM group. The iron accumulation was detected in the liver of all the patients with thalassemia. The gingival iron accumulation was correlated with neither serum ferritin levels nor hepatic iron accumulations. CONCLUSIONS: The periodontal tissues are affected by iron accumulation as well as hepatic, cardiac, and endocrine tissues in TM patients. Further studies investigating the usage of the gingival biopsy for prediagnosis of body iron overload in TM patients are needed.