Use of ATP Bioluminescence Assay to Evaluate Oral Streptococci.

The statistical correlation between the number of oral streptococci and the results of ATP bioluminescence assay was examined and compared with the results from Streptococcus plate counts and an oral bacteria quantification system. Because a significant correlation was found between ATP (RLU) and the number of bacteria in the oral bacteria quantification system for all seven types of oral streptococci examined, ATP would reflect a conditions of oral hygiene. However, using this assay, it was observed it may be difficult to correctly evaluate bacteria that form aggregates. Furthermore, even a small number of bacteria (below 105 CFU/mL) , which cannot be measured by the oral bacteria quantification system, could be estimated by using ATP bioluminescence assay. It was suggested that this assay could be used for quantitative evaluation of the effect of oral cleaning.

Protective effects of resveratrol against 5-fluorouracil-induced oxidative stress and inflammatory responses in human keratinocytes.

Although 5-fluorouracil (5-FU) is currently used as an anti-cancer chemotherapy, adverse effects such as oral mucositis potentially limit its clinical application. Additionally, the prevention of 5-FU-induced side effects are scarce. Resveratrol is known to decrease oxidative damage and inflammation. In this study, we examined the protective effects of resveratrol on 5-FU-induced oxidative stress and inflammatory responses in normal human keratinocytes (HaCaT cell) as in vitro oral mucositis model. HaCaT cells were exposed to 5-FU and simultaneously treated with resveratrol. The effects of resveratrol on 5-FU-induced cytotoxicity were evaluated using cell viability assay. The production of reactive oxygen species (ROS) was measured using a fluorescence spectrophotometer. The effects of resveratrol on nuclear factor erythroid 2-related factor 2 (Nrf2), silent information regulator transcript-1 (SIRT-1), and nuclear factor kappa B (NF-κB) signaling and inflammatory cytokine expression were examined. Resveratrol suppressed 5-FU-induced overproduction of ROS by upregulating anti-oxidant defense genes through Nrf2 activation and SIRT-1 expression. Concerning inflammatory responses, resveratrol suppressed the 5-FU-induced expression of pro-inflammatory cytokines via NF-κB nuclear translocation. Conversely, N-acetylcysteine reduced ROS levels without affecting the expression of pro-inflammatory cytokines. Resveratrol might be useful for preventing 5-FU-induced adverse effects by activating anti-oxidant and anti-inflammatory responses.

A survey of Lasioderma serricorne (Fabricius) in Japanese Dental Clinics.

This study was to survey the capturing rate in Japanese dental clinics of the Lasioderma serricorne (cigarette beetles) , and to evaluate the beetle's potential as a carrier for transmission of nosocomial pathogens. L. serricorne imagoes were captured in pheromone traps in 14 Japanese dental clinics in August and September 2012 and 2013, and their numbers recorded. Polymerase chain reaction (PCR) for the bacterial antibiotic-resistant genes mecA, vanA, vanB, blaIMP, and blaVIM was performed on the captured L. serricorne imagoes. Bacterial species in the captured specimens were identified by 16S rRNA PCR and sequencing analysis. The L. serricorne imagoes were captured from 10 dental clinics (71.4%) . We failed to detect the presence of nosocomial antibiotic-resistant pathogens in L. serricorne imagoes. The bacterial species detected most commonly in the imagoes was Wolbachia sp., an intracellular proteobacterium infecting certain insect species. Monitoring of insects including L. serricorne should be incorporated into regiment of the infection control.

The Serum Oxidative/Anti-oxidative Stress Balance Becomes Dysregulated in Patients with Non-alcoholic Steatohepatitis Associated with Hepatocellular Carcinoma.

Objective Oxidative stress is associated with the progression of chronic liver disease. Non-alcoholic fatty liver disease (NAFLD) is also an oxidative stress-related disease. However, the oxidative/anti-oxidative balance has not been fully characterized in NAFLD. The objective of the present study was to investigate the balance between oxidative stress and the anti-oxidative activity in NAFLD, including non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC). Patients We recruited 69 patients with histologically proven NAFLD without HCC (NAFLD; n=58), and with NASH-related HCC (NASH-HCC; n=11). The 58 NAFLD patients included patients with non-alcoholic fatty liver (NAFL; n=14) and NASH (n=44). Methods The serum levels of reactive oxygen metabolites (ROM) and anti-oxidative markers (OXY) were determined and then used to calculate the oxidative index. The correlations among such factors as ROM, OXY, oxidative index, and clinical characteristics were investigated. Results In NAFLD, ROM positively correlated with the body mass index (BMI), hemoglobin A1c (HbA1c), C-reactive protein (CRP), and the histological grade or inflammatory scores, while only high HbA1c and CRP levels were significant factors that correlated with a higher ROM according to a multivariate analysis. OXY positively correlated with the platelet counts, albumin, and creatinine levels, while negatively correlating with age. However, it improved after treatment intervention. The oxidative index positively correlated with BMI, CRP, and HbA1c. The NASH-HCC patients exhibited a lower OXY than the NASH patients, probably due to the effects of aging. Conclusion Oxidative stress correlated with the levels of NASH activity markers, while the anti-oxidative function was preserved in younger patients as well as in patients with a well-preserved liver function. The NASH-HCC patients tended to be older and exhibited a diminished anti-oxidative function.

Preventive effects of mouthguard use while sleeping on recurrent aphthous stomatitis: Preliminary interventional study.

Recurrent aphthous stomatitis (RAS) is the most common inflammatory ulceration in the oral mucosa of otherwise healthy individuals and is often accompanied by severe pain. However, the etiology of RAS is not completely understood, and currently, no therapy can completely prevent RAS recurrence. In our clinical experience, we noticed that patients using a night guard, which is often used for bruxism treatment, did not develop RAS. Therefore, the aim of this study was to determine whether mouthguard use can suppress RAS development. The cohort of this interventional, prospective, single-center, and self-controlled study included 20 subjects who developed RAS at least once a month. The oral health of all the subjects was recorded for 60 days before and after intervention with a mouthguard. The average number of RAS incidences decreased from 5.5 to 1.0, the average days until healing decreased from 7.3 to 5.6, and the period with RAS decreased from 31.5 to 5.0 with mouthguard use. Mouthguard use may be beneficial for preventing RAS development.

Molecular analysis for bacterial contamination in dental unit water lines.

Bacterial contamination in dental unit waterlines (DUWLs) was evaluated by molecular techniques in addition to the conventional culture method. Water samples (n=8) from DUWLs were investigated for heterotrophic bacteria by culture method using R2A agar. The selected bacterial antibiotic-resistance genes and Legionella species-specific 16SrDNA were identified by PCR. The profiles of bacterial contamination in DUWLs were further identified by PCR-DGGE. In this study, no antibiotic-resistant or Legionella genes were detected. Polycyclic aromatic hydrocarbon-degrading bacterium, Novosphingobium sp. was the most prevalent in DUWLs. Conventional PCR and PCR-DGGE were shown to be potentially useful for monitoring of bacterial contamination in DUWLs.

Oxidative stress balance is dysregulated and represents an additional target for treating cholangiocarcinoma.

BACKGROUND: Pancreatico-biliary malignancies exhibit similar characteristics, including obesity-related features and poor prognosis, and require new treatment strategies. Oxidative stress is known to induce DNA damage and carcinogenesis, and its reduction is viewed as being favorable. However, it also has anti-infection and anti-cancer functions that need to be maintained. To reveal the effect of oxidative stress on cancer progression, we evaluated oxidative stress and anti-oxidative balance in pancreatic cancer (PC) and cholangiocarcinoma (CC) patients, as well as the effect of add-on antioxidant treatment to chemotherapy in a mouse cholangiocarcinoma model. METHODS: We recruited 84 CC and 80 PC patients who were admitted to our hospital. Serum levels of reactive oxygen metabolites (ROM) and the anti-oxidative OXY-adsorbent test were determined and the balance of these tests was defined as an oxidative index. A diabetic mouse-based cholangiocarcinoma model was utilized to evaluate the effects of add-on antioxidant therapy on cholangiocarcinoma chemotherapy. RESULTS: Serum ROM was higher and anti-oxidant OXY was lower in CC patients with poor outcomes. These parameters were not significantly different in PC patients. In mice, vitamin E administration induced antioxidant hemeoxygenase (HO)-1 protein expression in cancer tissue, while the number of stem-like cells increased. l-carnitine administration improved intestinal microbiome and biliary acid balance, upregulated the hepatic mitochondrial membrane uptake related gene Cpt1 in non-cancerous tissue, and did not alter stem-like cell numbers. CONCLUSION: Oxidative stress balance was dysregulated in cholangiocarcinoma with poor outcome. The mitochondrial function-supporting agent l-carnitine is a good candidate to control oxidative stress conditions.

Hydrogen-Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model.

The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses.

Serum Oxidative/anti-oxidative Stress Balance Is Dysregulated in Potentially Pulmonary Hypertensive Patients with Liver Cirrhosis: A Case Control Study.

OBJECTIVE: Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH. METHODS: We recruited patients with decompensated cirrhosis (n=69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolar-arterial oxygen gradient (AaDO2) ≥15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient ≥25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXY-adsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a cross-sectional study. RESULTS: Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p=0.037) and higher oxidative index values (p=0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p=0.049). The potential POPH patients exhibited elevated AaDO2, suggesting the presence of pulmonary shunting. CONCLUSION: Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.

Relationship among salivary antioxidant activity, cytokines, and periodontitis: the Nagasaki Island study.

AIM: Antioxidant activities and cytokine levels in human body fluids are considered to be strongly associated with periodontitis. The aim of this study was to elucidate the relationship between salivary antioxidant activities against superoxide or hydroxyl radical, cytokines, and periodontal conditions through a community-based cross-sectional study conducted in Goto city, Japan. MATERIALS AND METHODS: Saliva samples were analysed for superoxide or hydroxyl radical scavenging activities and cytokine levels from 160 participants. We demonstrated that saliva contained superoxide and hydroxyl radical scavenging activities by using electron spin resonance with a spin-trapping agent. The concentrations of eight cytokines were measured using multiplex bead assays. RESULTS: There were significant differences in salivary superoxide or hydroxyl radical scavenging activity, and the levels of Interleukin-1ß, Interleukin-6, and Interleukin-8 between periodontitis classifications. Multivariate stepwise logistic regression model showed that salivary superoxide and hydroxyl radical scavenging activities were significantly associated with the classification of periodontitis. In addition, salivary superoxide scavenging activity was found to have significant association with all periodontal parameters using multiple linear regression analysis. CONCLUSIONS: These findings suggest that the evaluation of salivary antioxidant activities, as assessed by electron spin resonance, are associated with periodontitis and various clinical variables in community-dwelling participants (ClinicalTrials.gov number NCT01742728).

Biological impacts of resveratrol, quercetin, and N-acetylcysteine on oxidative stress in human gingival fibroblasts.

In periodontitis, production of reactive oxygen species (ROS) by neutrophils induces oxidative stress and deteriorates surrounding tissues. Antioxidants reduce damage caused by ROS and are used to treat diseases involving oxidative stress. This study summarizes the different effects of resveratrol, quercetin, and N-acetylcysteine (NAC) on human gingival fibroblasts (HGFs) under oxidative stress induced by hydrogen peroxide. Real-time cytotoxicity analyses reveals that resveratrol and quercetin enhanced cell proliferation even under oxidative stress. Of the antioxidants tested, resveratrol is the most effective at inhibiting ROS production. HGFs incubated with resveratrol and quercetin up-regulate the transcription of type I collagen gene after 3 h, but only resveratrol sustained this up-regulation for 24 h. A measurement of the oxygen consumption rate (OCR, mitochondrial respiration) shows that resveratrol generates the highest maximal respiratory capacity, followed by quercetin and NAC. Simultaneous measurement of OCR and the extracellular acidification rate (non-mitochondrial respiration) reveals that resveratrol and quercetin induce an increase in mitochondrial respiration when compared with untreated cells. NAC treatment consumes less oxygen and enhances more non-mitochondrial respiration. In conclusion, resveratrol is the most effective antioxidant in terms of real-time cytotoxicity analysis, reduction of ROS production, and enhancement of type I collagen synthesis and mitochondrial respiration in HGFs.

Resveratrol improves oxidative stress and prevents the progression of periodontitis via the activation of the Sirt1/AMPK and the Nrf2/antioxidant defense pathways in a rat periodontitis model.

Oxidative stress is a key factor regulating the systemic pathophysiological effects associated with periodontitis. Resveratrol is a phytochemical with antioxidant and anti-inflammatory properties that can reduce oxidative stress and inflammation. We hypothesized that resveratrol may prevent the progression of periodontitis and reduce systemic oxidative stress through the activation of the sirtuin 1 (Sirt1)/AMP-activated protein kinase (AMPK) and the nuclear factor E2-related factor 2 (Nrf2)/antioxidant defense pathways. Three groups of male Wistar rats (periodontitis treated with melinjo resveratrol, periodontitis without resveratrol, and control rats with no periodontitis or resveratrol treatment) were examined. A ligature was placed around the maxillary molars for 3 weeks to induce periodontitis, and the rats were then given drinking water with or without melinjo resveratrol. In rats with periodontitis, ligature placement induced alveolar bone resorption, quantified using three-dimensional images taken by micro-CT, and increased proinflammatory cytokine levels in gingival tissue. Melinjo resveratrol intake relieved alveolar bone resorption and activated the Sirt1/AMPK and the Nrf2/antioxidant defense pathways in inflamed gingival tissues. Further, melinjo resveratrol improved the systemic levels of 8-hydroxydeoxyguanosine, dityrosine, nitric oxide metabolism, nitrotyrosine, and proinflammatory cytokines. We conclude that oral administration of melinjo resveratrol may prevent the progression of ligature-induced periodontitis and improve systemic oxidative and nitrosative stress.

Longitudinal relationship between plasma reactive oxygen metabolites and periodontal condition in the maintenance phase of periodontal treatment.

AIM: The present cohort study describes the longitudinal relationship between plasma oxidative status and periodontitis progression during the maintenance phase of treatment. MATERIALS AND METHODS: Forty-five patients (mean age 58.8 years) were monitored from 2008 to 2013. Periodontal conditions, including probing pocket depth (PPD) and clinical attachment level (CAL), were recorded. Measurements of plasma reactive oxygen metabolites (ROM) and biologic antioxidant potential (BAP) were performed to evaluate plasma oxidative status. The patients were assigned into 2 groups as low and high plasma ROM level using a cut-off value which was median of plasma ROM level at baseline. RESULTS: In the subjects with low plasma ROM level at baseline, changes in mean CAL were positively correlated with changes in plasma ROM levels, bleeding on probing, and plaque control record, but not with PPD. In the subjects with high plasma ROM at baseline, changes in CAL were significantly associated with only PPD at baseline. On the other hands there were no significant associations between changes in CAL and those in plasma BAP levels. CONCLUSIONS: When plasma ROM level in periodontitis patients was low, increases in plasma ROM level were associated with those in CAL during the maintenance phase of treatment.

Anti-ageing effects of dentifrices containing anti-oxidative, anti-inflammatory, and anti-bacterial agents (Tomarina®) on gingival collagen degradation in rats.

OBJECTIVE: Previous studies have demonstrated the relationship between ageing and oxidative stress. In this study, we examined the effects of topical application of a dentifrice containing anti-oxidative, anti-inflammatory, and anti-bacterial agents (Tomarina®) to the gingival surface on gingival collagen degradation in rats. DESIGN: Fischer 344 male rats (4 or 8 months old) were divided into two groups: experimental group and control group. Tomarina® (the experimental group) or control dentifrice (the control group) was applied 5 days per week for 2 months. RESULTS: In the control group, gingival collagen density decreased with ageing. In the experimental group, the collagen density did not change with ageing, and was greater than that in the control group at 10 months of age (p < 0.0083). In addition, the control group showed an increase in serum oxidative stress with ageing. The experimental group also showed increased serum oxidative stress, but the value was lower than the control group at 10 months of age (p < 0.0083). Furthermore, low expressions of protein oxidative damage in the periodontal tissue were observed in the experimental group, compared to the control group at 6 months and 10 months. CONCLUSION: These findings indicate that Tomarina® might suppress the effects of ageing on gingival collagen degradation, by decreasing oxidative stress in the rat model.

Association of gingival recession and other factors with the presence of dentin hypersensitivity.

Dentin hypersensitivity (DH) may be present in association with gingival recession. The aim of this study was to determine quantitatively the association of gingival recession and other factors with the presence of DH. One hundred and four Japanese subjects with or without gingival recession were randomly selected. Intact canines and/or first premolars in both maxillary and mandibular quadrants were analyzed. Gingival recession was measured as a vertical length at the buccal site of the teeth. DH was recorded as an ordered categorical variable registering four increasing levels of pain after cold stimulation; from no discomfort to severe pain during and after stimulation (DH1, 2, 3, and 4). Association of DH with periodontal parameters and daily lifestyle was also investigated. Tooth-based analysis of 446 teeth from 104 subjects revealed that DH level was significantly higher in recessive teeth (1, 2, 3, and 4-8 mm) than in non-recessive teeth (0 mm). DH-positive rate in non-recessive teeth was only 18 % (DH1; 14 %, DH2; 3 %, and DH3; 1 %). Highest DH level was observed in teeth with severe recession (4-8 mm), showing DH0; 21 %, DH1; 33 %, DH2; 31 %, and DH3; 15 %. Recession-dependent increase in DH was observed, showing 18, 49, 52, 60, and 79 % DH-positive in teeth with 0, 1, 2, 3, and 4-8 mm recession, respectively. Plaque-free teeth showed a higher DH level than plaque-stained teeth, suggesting that good plaque control may be associated with the presence of DH. There were no significant differences in DH of teeth on the basis of smoking, probing depth, and bleeding on probing. Multiple logistic regression analysis revealed that gingival recession [odds ratio (OR) = 10.2, 95 % confidence interval (CI) = 5.5-18.9] and plaque deposition (OR = 0.3, 95 % CI = 0.2-0.5) were significant contributors to DH. Multilevel modeling analysis revealed that not only gingival recession and plaque deposition but also V-shaped cervical notch and tooth brushing frequency were associated with DH. These results demonstrate that the progression of gingival recession, plaque-free teeth, V-shaped cervical notch, and frequent brushing may be significant predictors of DH in canines and first premolars.

Effects of biliverdin administration on acute lung injury induced by hemorrhagic shock and resuscitation in rats.

Hemorrhagic shock and resuscitation induces pulmonary inflammation that leads to acute lung injury. Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects. This study aimed to examine the effects of intravenous biliverdin administration on lung injury induced by hemorrhagic shock and resuscitation in rats. Biliverdin or vehicle was administered to the rats 1 h before sham or hemorrhagic shock-inducing surgery. The sham-operated rats underwent all surgical procedures except bleeding. To induce hemorrhagic shock, rats were bled to achieve a mean arterial pressure of 30 mmHg that was maintained for 60 min, followed by resuscitation with shed blood. Histopathological changes in the lungs were evaluated by histopathological scoring analysis. Inflammatory gene expression was determined by Northern blot analysis, and oxidative DNA damage was assessed by measuring 8-hydroxy-2' deoxyguanosine levels in the lungs. Hemorrhagic shock and resuscitation resulted in prominent histopathological damage, including congestion, edema, cellular infiltration, and hemorrhage. Biliverdin administration prior to hemorrhagic shock and resuscitation significantly ameliorated these lung injuries as judged by histopathological improvement. After hemorrhagic shock and resuscitation, inflammatory gene expression of tumor necrosis factor-α and inducible nitric oxide synthase were increased by 18- and 8-fold, respectively. Inflammatory gene expression significantly decreased when biliverdin was administered prior to hemorrhagic shock and resuscitation. Moreover, after hemorrhagic shock and resuscitation, lung 8-hydroxy-2' deoxyguanosine levels in mitochondrial DNA expressed in the pulmonary interstitium increased by 1.5-fold. Biliverdin administration prior to hemorrhagic shock and resuscitation decreased mitochondrial 8-hydroxy-2' deoxyguanosine levels to almost the same level as that in the control animals. We also confirmed that biliverdin administration after hemorrhagic shock and resuscitation had protective effects on lung injury. Our findings suggest that biliverdin has a protective role, at least in part, against hemorrhagic shock and resuscitation-induced lung injury through anti-inflammatory and anti-oxidant mechanisms.

Serum oxidative-anti-oxidative stress balance is dysregulated in patients with hepatitis C virus-related hepatocellular carcinoma.

AIM: Oxidative stress is associated with progression of chronic liver disease (CLD). This association is best established in chronic hepatitis C. However, the anti-oxidative state is not well characterized. The objective of the present study was to investigate the balance of oxidative and anti-oxidative stress in CLD patients. METHODS: We recruited a study population of 208 patients, including healthy volunteers (HV; n = 15), patients with hepatitis B virus (HBV)-related CLD without or with hepatocellular carcinoma (HBV-non-HCC, n = 25, and HBV-HCC, n = 50, respectively), and patients with hepatitis C virus (HCV)-related CLD without or with HCC (HCV-non-HCC, n = 49, and HCV-HCC, n = 69, respectively). Serum levels of reactive oxygen metabolites (ROM) and anti-oxidative markers (OXY-adsorbent test; OXY) were determined, and the balance of these values was used as the oxidative index. Correlations among ROM, OXY, oxidative index and clinical characteristics were investigated. RESULTS: Patients with CLD exhibited elevated ROM and oxidative index compared to HV. Among patients with CLD, HCV positive status correlated with increased ROM. In CLD, HCV-HCC patients exhibited the highest ROM levels. Among HCV-related CLD patients, lower OXY correlated with HCC positive status, but was recovered by eradication of HCC. In HCV-HCC, lower OXY correlated with high PT-INR. CONCLUSION: HCV positive CLD patients displayed higher oxidative stress and HCV-HCC patients displayed lower anti-oxidative state. Anti-oxidative state depression was associated with liver reservoir-related data in HCV-HCC and could be reversed with HCC eradication.

Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model.

OBJECTIVE: Periodontitis has been causally linked to atherosclerosis, which is mediated by the oxidative stress. As hydrogen-rich water (HW) scavenges reactive oxygen species (ROS), we hypothesized that HW could prevent lipid deposition induced by periodontitis in the aorta. The aim of this study was to investigate the effects of HW on the initiation of atherosclerosis in a rat periodontitis model. DESIGN: Eighteen 8-wk-old male Wistar rats were divided into three groups of six rats; the periodontitis group, periodontitis+HW group and the no treatment (control) group. In the periodontitis and periodontitis+HW groups, periodontitis was induced using a ligature for 4 wk, while the periodontitis+HW group was given water containing 800-1000 µg/L hydrogen during the 4-wk experimental period. RESULTS: In the periodontitis group, lipid deposition in the descending aorta was observed. The periodontitis group also showed significant higher serum levels for ROS and oxidised low-density lipoprotein-cholesterol (ox-LDL) (1.7 and 1.4 times, respectively), and higher aortic expression levels of nitrotyrosine and hexanoyl-lysine (HEL) (7.9 and 16.0 times, respectively), as compared to the control group (p<0.05). In the periodontitis+HW group, lipid deposition was lower. Lower serum levels of ROS and ox-LDL (0.46 and 0.82 times, respectively) and lower aortic levels of nitrotyrosine and HEL (0.27 and 0.19 times, respectively) were observed in the periodontitis+HW group than in the periodontitis group (p<0.05). CONCLUSIONS: HW intake may prevent lipid deposition in the rat aorta induced by periodontitis by decreasing serum ox-LDL levels and aortic oxidative stress.

Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice.

UNLABELLED: Oxidative stress is a strong contributor to the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). Molecular hydrogen is an effective antioxidant that reduces cytotoxic reactive oxygen species. In this study, we investigated the effects of hydrogen-rich water and the drug pioglitazone on the progression of NASH in mouse models. A methionine-choline-deficient (MCD) diet mouse model was prepared. Mice were divided into three experimental groups and fed for 8 weeks as follows: (1) MCD diet + control water (CW group); (2) MCD diet + hydrogen-rich water (HW group); and (3) MCD diet mixed with pioglitazone (PGZ group). Plasma alanine aminotransferase levels, hepatic expression of tumor necrosis factor-α, interleukin-6, fatty acid synthesis-related genes, oxidative stress biomarker 8-hydroxydeoxyguanosine (8-OHdG), and apoptosis marker terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells in the liver were decreased in the HW and PGZ groups. The HW group showed a smaller decrease in hepatic cholesterol; however, stronger antioxidative effects in serum and lower peroxisome proliferator-activated receptor-α expression in the liver were seen in comparison with the PGZ group. We then investigated the effects of hydrogen in the prevention of hepatocarcinogenesis in STAM mice, known as the NASH-related hepatocarcinogenesis model. Eight-week-old male STAM mice were divided into three experimental groups as follows: (1) control water (CW-STAM); (2) hydrogen-rich water (HW-STAM); and (3) pioglitazone (PGZ-STAM). After 8 weeks, hepatic tumors were evaluated. The number of tumors was significantly lower in the HW-STAM and PGZ-STAM groups than in the CW-STAM group. The maximum tumor size was smaller in the HW-STAM group than in the other groups. CONCLUSION: Consumption of hydrogen-rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis.

Stage of hepatocellular carcinoma is associated with periodontitis.

AIM: Periodontitis induces overproduction of reactive oxygen species (ROS). This state increases circulating ROS levels and may affect hepatocellular carcinoma (HCC). The Japan Integrated Stage (JIS) score is a novel staging system for HCC. The objective of the present study was to compare JIS scores in HCC patients with and without periodontitis. MATERIAL AND METHODS: We recruited 64 HCC patients comprising 31 chronic periodontitis subjects (HCC + P) and 33 periodontally healthy controls (HCC + H). Their JIS scores were recorded. Serum levels of reactive oxygen metabolites (ROM) from HCC + P, HCC + H and healthy age- and gender-matched subjects with healthy gingiva (control, n = 15) were also assessed for circulating ROS levels. RESULTS: The HCC + P and HCC + H groups had similar body mass index, habitual drinking and tobacco exposure data. The HCC + P group showed higher JIS scores than the HCC + H group (p = 0.027). Both the HCC + P and HCC + H groups had higher serum levels of ROM than controls (p < 0.001), while serum levels of ROM in the HCC + P group were a further 25.8% higher than those in the HCC + H group (p < 0.001). CONCLUSION: HCC patients with periodontitis had higher JIS score and circulating ROS level than HCC patients without periodontitis.