Salivary Gland Dysfunction in Stroke Patients Is Associated with Increased Protein Glycoxidation and Nitrosative Stress

Stroke is one of the leading causes of disability and death worldwide. Despite intensive medical care, many of the complaints directly threatening the patient’s life marginalize their dental needs after the stroke. Recent studies indicate reduced saliva secretion in stroke patients in addition to the increased incidence of caries and periodontal disease. Since oxidative stress plays a vital role in the pathogenesis of salivary gland hypofunction and neurodegenerative disorders (including stroke), this is the first to evaluate the relationship between salivary gland activity and protein glycoxidation and nitrosative damage. The content of glycation and protein oxidation products and nitrosative stress was assessed in nonstimulated (NWS) and stimulated (SWS) whole saliva of stroke patients with normal salivary secretion and hyposalivation (reduced saliva production). The study included 30 patients in the stroke’s subacute phase and 30 healthy controls matched by age and sex. We have shown that stroke patients with hyposalivation show increased contents of protein glycation (↑Amadori products and ↑advanced glycation end products), glycoxidation (↑dityrosine), and nitration (↑nitrotyrosine) products compared to stroke cases with normal salivary secretion and control group. Interestingly, higher oxidative/nitrosative stress was found in NWS, which strongly correlates with salivary flow rate, total protein content, and salivary amylase activity. Such relationships were not observed in the control group. Summarizing, oxidative and nitrosative stress may be one of the mechanisms responsible for the impairment of saliva secretion in stroke patients. However, extraglandular sources of salivary oxidative stress in stroke patients cannot be excluded. Further studies to assess salivary gland hypofunction in stroke cases are necessary.

Download Full-text

NAC Supplementation of Hyperglycemic Rats Prevents the Development of Insulin Resistance and Improves Antioxidant Status but Only Alleviates General and Salivary Gland Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/8831855 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Anna Zalewska ◽

Sara Zięba ◽

Paula Kostecka-Sochoń ◽

Agnieszka Kossakowska ◽

Małgorzata Żendzian-Piotrowska ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Salivary Gland ◽

High Fat Diet ◽

Antioxidant Status ◽

High Fat ◽

Protein Levels ◽

Saliva Secretion ◽

Whole Saliva ◽

Oxidative Modifications

Previous studies based on animal models demonstrated that N-acetylcysteine (NAC) prevents oxidative stress and improves salivary gland function when the NAC supplementation starts simultaneously with insulin resistance (IR) induction. This study is the first to evaluate the effect of a 4-week NAC supply on the antioxidant barrier and oxidative stress in Wistar rats after six weeks of high-fat diet (HFD) intake. Redox biomarkers were evaluated in the parotid (PG) and submandibular (SMG) salivary glands and stimulated whole saliva (SWS), as well as in the plasma and serum. We demonstrated that the activity of salivary peroxidase and superoxide dismutase and total antioxidant capacity were significantly higher in PG, SMG, and SWS of IR rats treated with NAC. It appears that in PG and SMG of rats fed an HFD, N-acetylcysteine supplementation abolishes oxidative modifications to proteins (evidenced by decreased content of advanced oxidation protein products (AOPP) and advanced glycation end products (AGE)). Simultaneously, it does not reverse oxidative modifications of lipids (as seen in increased concentration of 8-isoprostanes and 4-hydroxynonenal vs. the control), although it reduces the peroxidation of salivary lipids in relation to the group fed a high-fat diet alone. NAC administration increased protein levels in PG and SMG but did not affect saliva secretion, which was significantly lower compared to the controls. To sum up, the inclusion of NAC supplementation after six weeks of HFD feeding was effective in improving the general and salivary gland antioxidant status. Nevertheless, NAC did not eliminate salivary oxidative stress and only partially prevented salivary gland dysfunction.

Download Full-text

Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction

Scientific Reports ◽

10.1038/s41598-021-86927-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xibao Liu ◽

Krishna P. Subedi ◽

Changyu Zheng ◽

Indu Ambudkar

Keyword(s):

Salivary Gland ◽

Caspase 3 ◽

Salivary Secretion ◽

Initial Increase ◽

Oral Infections ◽

Saliva Secretion ◽

Salivary Gland Secretion ◽

Radiation Induced ◽

Salivary Gland Hypofunction ◽

Gland Function

AbstractA severe consequence of radiation therapy in patients with head and neck cancer is persistent salivary gland hypofunction which causes xerostomia and oral infections. We previously showed that irradiation (IR) of salivary glands in mice triggers initial transient increases in mitochondrial reactive oxygen species (ROSmt), mitochondrial [Ca2+] ([Ca2+]mt), and activated caspase-3 in acinar cells. In contrast, loss of salivary secretion is persistent. Herein we assessed the role of ROSmt in radiation-induced irreversible loss of salivary gland function. We report that treatment of mice with the mitochondrial-targeted antioxidant, MitoTEMPO, resulted in almost complete protection of salivary gland secretion following either single (15 Gy) or fractionated (5 × 3 Gy) doses of irradiation. Salivary gland cells isolated from MitoTEMPO-treated, irradiated, mice displayed significant attenuation of the initial increases in ROSmt, ([Ca2+]mt, and activated caspase-3 as compared to cells from irradiated, but untreated, animals. Importantly, MitoTEMPO treatment prevented radiation-induced decrease in STIM1, consequently protecting store-operated Ca2+ entry which is critical for saliva secretion. Together, these findings identify the initial increase in ROSmt, that is induced by irradiation, as a critical driver of persistent salivary gland hypofunction. We suggest that the mitochondrially targeted antioxidant, MitoTEMPO, can be potentially important in preventing IR-induced salivary gland dysfunction.

Download Full-text

Salivary Gland Dysfunction, Protein Glycooxidation and Nitrosative Stress in Children with Chronic Kidney Disease

Journal of Clinical Medicine ◽

10.3390/jcm9051285 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1285 ◽

Cited By ~ 11

Author(s):

Mateusz Maciejczyk ◽

Julita Szulimowska ◽

Katarzyna Taranta-Janusz ◽

Anna Wasilewska ◽

Anna Zalewska

Keyword(s):

Chronic Kidney Disease ◽

Salivary Gland ◽

Kidney Disease ◽

Nitrosative Stress ◽

Amylase Activity ◽

Salivary Secretion ◽

Oxidation Products ◽

Total Protein Content ◽

Salivary Gland Dysfunction ◽

Saliva Secretion

This study is the first to evaluate protein glycooxidation products, lipid oxidative damage and nitrosative stress in non-stimulated (NWS) and stimulated whole saliva (SWS) of children with chronic kidney disease (CKD) divided into two subgroups: normal salivary secretion (n = 18) and hyposalivation (NWS flow < 0.2 mL min−1; n = 12). Hyposalivation was observed in all patients with severe renal failure (4–5 stage CKD), while saliva secretion > 0.2 mL/min in children with mild-moderate CKD (1–3 stage) and controls. Salivary amylase activity and total protein content were significantly lower in CKD children with hyposalivation compared to CKD patients with normal saliva secretion and control group. The fluorescence of protein glycooxidation products (kynurenine, N-formylkynurenine, advanced glycation end products), the content of oxidative damage to lipids (4-hydroxynonneal, 8-isoprostanes) and nitrosative stress (peroxynitrite, nitrotyrosine) were significantly higher in NWS, SWS, and plasma of CKD children with hyposalivation compared to patients with normal salivary secretion and healthy controls. In CKD group, salivary oxidation products correlated negatively with salivary flow rate, α-amylase activity and total protein content; however, salivary oxidation products do not reflect their plasma level. In conclusion, children with CKD suffer from salivary gland dysfunction. Oxidation of salivary proteins and lipids increases with CKD progression and deterioration of salivary gland function.

Download Full-text

Older age, smoking, tooth loss and denture-wearing but neither xerostomia nor salivary gland hypofunction are associated with low intakes of fruit and vegetables in older Danish adults

Journal of Nutritional Science ◽

10.1017/jns.2021.38 ◽

2021 ◽

Vol 10 ◽

Author(s):

Anne Marie Lynge Pedersen ◽

Anja Weirsøe Dynesen ◽

Berit Lilienthal Heitmann

Keyword(s):

Salivary Gland ◽

Tooth Loss ◽

Vegetable Intake ◽

Community Dwelling ◽

Older Age ◽

Fruit And Vegetables ◽

Fruit And Vegetable ◽

Flow Rates ◽

Whole Saliva ◽

Salivary Gland Hypofunction

Abstract Xerostomia and salivary gland hypofunction are prevalent conditions in older people and may adversely influence the intake of certain foods, notably fruit and vegetables. Here, we aimed to investigate whether xerostomia and salivary gland hypofunction were associated with a lower intake of fruit and vegetables. The study included 621 community-dwelling adults, mean age 75⋅2 ± 6⋅4 years, 58⋅9 % female, who had participated in the Copenhagen City Heart Study follow-up, and undergone interviews regarding food intake (preceding month), oral and general health (xerostomia, taste alterations, diseases, medication, alcohol consumption and smoking), clinical oral examination and measurements of unstimulated and chewing-stimulated whole saliva flow rates. The average total energy intake (8⋅4 ± 2⋅7 MJ) and protein energy percentage (14⋅8 ± 3⋅1 %) were slightly below recommendations. The average fruit (234⋅7 ± 201⋅2 g/d) and vegetables (317⋅3 ± 157⋅4 g/d) intakes were within recommendations. Xerostomia and hyposalivation were more prevalent in women than in men (16⋅4 v. 7⋅1 %, P < 0⋅001 and 40⋅7 v. 27⋅5 %, P < 0⋅001). Multiple linear regression analyses revealed that older age (β −0⋅009, se 0⋅003, P = 0⋅005), smoking (β −0⋅212, se 0⋅060, P = 0⋅0005) and wearing complete dentures/being partially or fully edentulous (β −0⋅141, se 0⋅048, P = 0⋅003), but neither xerostomia nor salivary flow rates were associated with an inadequate fruit and vegetable intake, after adjustment for covariates. Older age, smoking, tooth loss and denture-wearing were stronger determinants of low fruit and vegetable intakes than xerostomia and salivary hypofunction supporting the importance of dietary counselling and maintenance of oral health and an adequate masticatory performance.

Download Full-text

Choline Acetyltransferase Induces the Functional Regeneration of the Salivary Gland in Aging SAMP1/Kl -/- Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22010404 ◽

2021 ◽

Vol 22 (1) ◽

pp. 404

Author(s):

Nguyen Khanh Toan ◽

Nguyen Chi Tai ◽

Soo-A Kim ◽

Sang-Gun Ahn

Keyword(s):

Salivary Gland ◽

Choline Acetyltransferase ◽

Salivary Flow ◽

Salivary Secretion ◽

Functional Markers ◽

Tooth Structure ◽

Saliva Secretion ◽

Gland Function ◽

The Impact

Salivary gland dysfunction induces salivary flow reduction and a dry mouth, and commonly involves oral dysfunction, tooth structure deterioration, and infection through reduced salivation. This study aimed to investigate the impact of aging on the salivary gland by a metabolomics approach in an extensive aging mouse model, SAMP1/Klotho -/- mice. We found that the salivary secretion of SAMP1/Klotho -/- mice was dramatically decreased compared with that of SAMP1/Klotho WT (+/+) mice. Metabolomics profiling analysis showed that the level of acetylcholine was significantly decreased in SAMP1/Klotho -/- mice, although the corresponding levels of acetylcholine precursors, acetyl-CoA and choline, increased. Interestingly, the mRNA and protein expression of choline acetyltransferase (ChAT), which is responsible for catalyzing acetylcholine synthesis, was significantly decreased in SAMP1/Klotho -/- mice. The overexpression of ChAT induced the expression of salivary gland functional markers (α–amylase, ZO-1, and Aqua5) in primary cultured salivary gland cells from SAMP1/Klotho +/+ and -/- mice. In an in vivo study, adeno-associated virus (AAV)-ChAT transduction significantly increased saliva secretion compared with the control in SAMP1/Klotho -/- mice. These results suggest that the dysfunction in acetylcholine biosynthesis induced by ChAT reduction may cause impaired salivary gland function

Download Full-text

Hyperglycemia Induces Generation of Reactive Oxygen Species and Accelerates Apoptotic Cell Death in Salivary Gland Cells

Pathobiology ◽

10.1159/000512639 ◽

2021 ◽

pp. 1-8

Author(s):

Naoyuki Matsumoto ◽

Daisuke Omagari ◽

Ryoko Ushikoshi-Nakayama ◽

Tomoe Yamazaki ◽

Hiroko Inoue ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Salivary Gland ◽

Tissue Injury ◽

Ros Production ◽

Oxygen Species ◽

Saliva Secretion ◽

Salivary Gland Tissue ◽

Gland Tissue

Introduction: Type-2 diabetes mellitus (T2DM) is associated with several systemic vascular symptoms and xerostomia. It is considered that hyperglycemia-induced polyuria and dehydration cause decreased body-water volume, leading to decreased saliva secretion and, ultimately, xerostomia. In T2DM, increased production of reactive oxygen species (ROS) causes tissue damage to vascular endothelial cells as well as epithelial tissue, including pancreas and cornea. Hence, a similar phenomenon may occur in other tissues and glands in a hyperglycemic environment. Methods: Salivary gland tissue injury was examined, using T2DM model mouse (db/db). Transferase‐mediated dUTP nick‐end labeling (TUNEL) was conducted to evaluate tissue injury. The levels of malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine, Bax/Bcl-2 ratio were measured as indicator of oxidative stress. Moreover, in vitro ROS production and cell injury was evaluated by mouse salivary gland-derived normal cells under high-glucose condition culture. Results: In vivo and in vitro analysis showed a higher percentage of TUNEL-positive cells and higher levels of MDA and 8-hydroxy-2′-deoxyguanosine in salivary gland tissue of db/db mice. This suggests damage of saliva secretion-associated lipids and DNA by hyperglycemic-induced oxidative stress. To analyze the mechanism by which hyperglycemia promotes ROS production, mouse salivary gland-derived cells were isolated. The cell culture with high-glucose medium enhanced ROS production and promotes apoptotic and necrotic cell death. Conclusion: These findings suggest a novel mechanism whereby hyperglycemic-induced ROS production promotes salivary gland injury, resulting in hyposalivation.

Download Full-text

Evaluation of Salivary and Serum Total Antioxidant Capacity and Lipid Peroxidation in Postmenopausal Women

International Journal of Dentistry ◽

10.1155/2020/8860467 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Fatemeh Zovari ◽

Hadi Parsian ◽

Ali Bijani ◽

Ameneh Moslemnezhad ◽

Atena Shirzad

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Antioxidant Capacity ◽

Postmenopausal Women ◽

Total Antioxidant Capacity ◽

Premenopausal Women ◽

Control Group ◽

Antioxidant Power ◽

Whole Saliva ◽

Total Antioxidant

Objective. In menopause, reduction of estrogen hormone affects oxidative stress process in serum. Oxidative stress in saliva plays a significant role in the pathogenesis of oral diseases. The aim of this study was to investigate the total antioxidant capacity and lipid peroxidation in the serum and saliva of premenopausal and postmenopausal women. Methods. In this case control study, 50 postmenopausal women (case group) and 48 premenopausal women (control group) were selected. The unstimulated whole saliva and serum of the postmenopausal and premenopausal women were collected. The total antioxidant capacity (TAC) of the saliva and serum was measured by ferric reducing antioxidant power (FRAP). Also, malondialdehyde (MDA) was measured by thiobarbituric acid reactive substance (TBARS) method for serum and saliva. Then, the obtained data were analyzed by SPSS 17, whereby Mann–Whitney test and Spearman’s correlation test were used. P < 0.05 was considered statistically significant. Results. The postmenopausal group had significantly lower mean serum TAC and higher mean serum MDA than the control group ( P < 0 < 001 and P < 0.01 , respectively). The mean salivary TAC and MDA, however, did not differ significantly between the case and control group ( P = 0.64 and P = 0.08 , respectively). Conclusion. In postmenopausal women, with elevation of serum MDA and reduction of serum TAC, the extent of serum oxidative stress grows, but MDA and TAC levels of saliva do not change.

Download Full-text

Dysfunction of Salivary Glands, Disturbances in Salivary Antioxidants and Increased Oxidative Damage in Saliva of Overweight and Obese Adolescents

Journal of Clinical Medicine ◽

10.3390/jcm9020548 ◽

2020 ◽

Vol 9 (2) ◽

pp. 548 ◽

Cited By ~ 9

Author(s):

Anna Zalewska ◽

Agnieszka Kossakowska ◽

Katarzyna Taranta-Janusz ◽

Sara Zięba ◽

Katarzyna Fejfer ◽

...

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Redox Homeostasis ◽

Salivary Secretion ◽

Control Group ◽

Total Protein Content ◽

Parotid Glands ◽

Obese Adolescents ◽

Total Antioxidant ◽

And Gender

Obesity is inseparably connected with oxidative stress. This process may disturb the functioning of the oral cavity, although the effect of oxidative stress on salivary gland function and changes in the qualitative composition of saliva are still unknown. Our study is the first to evaluate salivary redox homeostasis in 40 overweight and obese adolescents and in the age- and gender-matched control group. We demonstrated strengthening of the antioxidant barrier (superoxide dismutase, catalase, peroxidase, uric acid, total antioxidant capacity (TAC)) with a simultaneous decrease in reduced glutathione concentration in saliva (non-stimulated/stimulated) in overweight and obese teenagers compared to the controls. The concentration of the products of oxidative damage to proteins (advanced glycation end products), lipids (malondialdehyde, 4-hydroxynonenal) and DNA (8-hydroxydeoxyguanosine) as well as total oxidative status were significantly higher in both non-stimulated and stimulated saliva as well as plasma of overweight and obese adolescents. Importantly, we observed more severe salivary and plasma redox alterations in obese adolescents compared to overweight individuals. In the study group, we also noted a drop in stimulated salivary secretion and a decrease in total protein content. Interestingly, dysfunction of parotid glands in overweight and obese teenagers intensified with the increase of BMI. We also showed that the measurement of salivary catalase and TAC could be used to assess the central antioxidant status of overweight and obese adolescents.

Download Full-text

Effects of Rosiglitazone with Insulin Combination Therapy on Oxidative Stress and Lipid Profile in Left Ventricular Muscles of Diabetic Rats

Experimental Diabetes Research ◽

10.1155/2012/905683 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Servet Kavak ◽

Lokman Ayaz ◽

Mustafa Emre

Keyword(s):

Oxidative Stress ◽

Blood Glucose ◽

Lipid Profile ◽

Nitrosative Stress ◽

Vascular Diseases ◽

Diabetic Rats ◽

Left Ventricular ◽

Control Group ◽

Group B ◽

Group D

Purpose. In this study, we tested the hypothesis that rosiglitazone (RSG) with insulin is able to quench oxidative stress initiated by high glucose through prevention of NAD(P)H oxidase activation.Methods and Materials. Male albino Wistar rats were randomly divided into an untreated control group (C), a diabetic group (D) that was treated with a single intraperitoneal injection of streptozotocin (45 mgkg−1), and rosiglitazone group that was treated with RSG twice daily by gavage and insulin once daily by subcutaneous injection (group B). HbA1c and blood glucose levels in the circulation and malondialdehyde and 3-nitrotyrosine levels in left ventricular muscle were measured.Result. Treatment of D rats with group B resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA1c levels in group B reached the control group D rat values at the end of the treatment period. There was an increase in 3-nitrotyrosine levels in group D compared to group C. Malondialdehyde and 3-nitrotyrosine levels were found to be decreased in group B compared to group D(P<0.05).Conclusion. Our data suggests that the treatment of diabetic rats with group B for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus, in diabetes-related vascular diseases, group B treatment may be cardioprotective.

Download Full-text

Salivary and Serum Antioxidant and Oxidative Stress Markers in Dental Caries

Caries Research ◽

10.1159/000488213 ◽

2018 ◽

Vol 52 (6) ◽

pp. 565-569 ◽

Cited By ~ 5

Author(s):

Fatemeh Ahmadi-Motamayel ◽

Mohammad Taghi Goodarzi ◽

Ali Mahdavinezhad ◽

Zohreh Jamshidi ◽

Mohammad Darvishi

Keyword(s):

Oxidative Stress ◽

Dental Caries ◽

Oral Disease ◽

Healthy Control Group ◽

Oxidative Stress Marker ◽

Control Group ◽

Control Groups ◽

Whole Saliva ◽

Healthy Control ◽

And Control

Dental caries is the most common, chronic, noncommunicable, preventable oral disease worldwide. Oxidation may play an important role in dental caries initiation and progression. Antioxidants in body fluids protect cells. The aim of this study was to evaluate salivary and serum total antioxidant capacity (TAC) and malondialdehyde (MDA) levels in dental caries. A total of 118 healthy caries-free and caries-active male and female students participated. Caries was detected clinically. Unstimulated whole-saliva samples and blood samples were obtained. Sialochemical analysis was carried out by spectrophotometric assay. Data were analyzed with the Student t test using STATA 11. Salivary and serum TAC levels in the case and control groups did not show any significant differences. Mean salivary MDA levels in the case and control groups were 0.71 ± 0.1 and 0.35 ± 0.06 nmol/mL, respectively. The results showed significantly higher levels of salivary and serum MDA in the case group compared to the healthy control group. The oxidative stress marker was significantly higher in the caries group compared to the healthy control group. Antioxidants were not significantly different between the two groups. MDA can be produced by dental caries, resulting in a decrease in antioxidant levels, causing disease progression. Further studies are necessary to determine whether MDA is the cause or effect of the disease.

Download Full-text