Altered redox homeostasis in human diabetes saliva.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of diabetes mellitus (DM). Levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-epi-prostaglandin-F(2α) (8-epi-PGF2α), and total protein carbonyls were measured to assess whether DM is associated with altered salivary redox homeostasis. METHODS: A total of 215 patients with diabetes and 481 healthy controls were recruited from the Department of Endocrinology at the Jewish General Hospital in Montreal. Levels of oxidative biomarkers were assayed using enzyme-linked immunosorbent assay (ELISA) in whole unstimulated saliva. Associations of the redox data with exposure to insulin, metformin and dietary control were assessed by logistic regression analyses. RESULTS: We observed (i) significantly higher mean levels of 8-OHdG and protein carbonyls in whole unstimulated saliva of patients with diabetes compared to controls, (ii) higher mean levels of protein carbonyls in type 1 diabetes as well as higher mean levels of 8-OHdG and protein carbonyls in type 2 diabetes compared to controls, (iii) elevated levels of protein carbonyls in diet-controlled patients and in patients with diabetes on insulin and metformin, (iv) elevated levels of 8-OHdG in patients on metformin, and (v) significant associations between subjects with DM and salivary 8-OHdG and protein carbonyls. CONCLUSION: DM is associated with increased oxidative modification of salivary DNA and proteins. Salivary redox homeostasis is perturbed in DM and may inform on the presence of the disease and efficacy of therapeutic interventions.

Altered salivary redox homeostasis in patients with systemic sclerosis.

OBJECTIVE: Oxidative stress has been implicated in the pathogenesis of systemic sclerosis (SSc). Our objective was to determine whether SSc is associated with altered redox homeostasis in human saliva. METHODS: Study participants were 70 women with SSc and 120 female controls. 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-epi-prostaglandin F 2alpha (8-epi-PGF2alpha), and total protein carbonyls were assayed by ELISA to quantify oxidative damage to nucleic acids, lipids, and proteins, respectively, in whole nonstimulated saliva. RESULTS: We observed a significantly positive association between salivary log protein carbonyls and SSc in a crude statistic (OR 9.06, p < 0.0001), and multivariable model adjusted for log 8-OHdG, log 8-epi-PGF2alpha, and antioxidant exposure (OR 9.26, p < 0.0001). No significant association was noted between SSc and salivary log 8-epi-PGF2alpha or log 8-OHdG. CONCLUSION: Salivary redox homeostasis is perturbed in patients with SSc and may inform on the pathophysiology and presence of the disease (biomarkers) and efficacy of therapeutic interventions.

Salivary DNA, lipid, and protein oxidation in nonsmokers with periodontal disease.

Reactive oxygen species (ROS) are implicated in the destruction of the periodontium during periodontitis. The imbalance in oxidant activity may be a key factor. The aim of this paper is to determine whether periodontitis is associated with increased oxidative damage to DNA, lipids, and proteins and modification of total antioxidant capacity (TAC) in saliva. Saliva was collected from 58 periodontitis patients and 234 healthy controls, all nonsmokers. Periodontal disease status was characterized using the Community Periodontal Index of Treatment Needs (CPITN). Assays for 8-OHdG (ELISA), 8-epi-PGF2alpha (ELISA), and total protein carbonyls (ELISA), and oxy-blotting (Western)/mass spectrometry were performed to quantify oxidative damage to nucleic acids, lipids, total and individual proteins, respectively, in whole nonstimulated saliva. Salivary TAC was measured by inhibition of ABTS oxidation by metmyoglobin. We observed (i) significantly higher levels of 8-OHdG, 8-epi-PGF2alpha, and carbonylated proteins in saliva of periodontal patients as compared with controls (P=0.0003, <0.0001 and <0.0001); (ii) 8-OHdG, 8-epi-PGF2alpha, and carbonylated proteins were independently negatively associated with CPITN (P=0.004, 0.02, and <0.0001); (iii) a positive correlation between salivary TAC and periodontal disease status in the study group (P<0.0001); and (iv) specific oxidation of transferrin, human IgG1 heavy chain fragment, and salivary amylase in periodontitis. Periodontal disease is associated with increased oxidative modification of salivary DNA, lipids, and proteins. Augmented salivary total antioxidant capacity may represent an adaptive response to oxidative stress. Salivary amylase, transferrin, and human IgG1 heavy chain fragments are particularly prone to enhanced oxidation in periodontitis.