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Alzheimer's disease (AD) is associated with the deposition of β-amyloid in the brain. AD accounts for over 50% of cases of dementia which results from disturbances in redox homeostasis. Indeed, increased intensity of protein oxidation and nitration as well as lipid peroxidation is observed in brain areas with considerable amounts of amyloid plaques and neurofibrillary tangles. However, little is known about the oxidoreductive balance of salivary glands in AD patients. Therefore, the aim of this study was to evaluate the antioxidant barrier and oxidative/nitrosative stress biomarkers in stimulated saliva and blood of AD patients. The study was participated by 25 AD patients and 25 non-demented controls without neurological diseases or cognitive impairment, matched by age and gender to the study group. The number of patients was determined based on a previous pilot study (test power = 0.9). We found a significant decrease in the activity of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx), increased activity of catalase (CAT) and reduced concentration of plasma non-enzymatic antioxidants (uric acid, UA and reduced glutathione, GSH). In contrast, in the stimulated saliva of AD patients we observed significantly decreased activity of all antioxidant enzymes (SOD, CAT and GPx) as well as concentration of GSH compared to the control group. The content of lipid (malondialdehyde, MDA) and protein (advanced oxidation protein products, AOPP; advanced glycation end-products, AGE) oxidation products as well as biomarkers of nitrosative stress (peroxynitrite, nitrotyrosine) was significantly higher in both saliva and plasma of AD patients compared to the controls. In AD patients, we also observed a considerable decrease in stimulated saliva secretion and salivary total protein content, and an increase in salivary β-amyloid concentration. In conclusion, AD results in redox imbalance towards oxidative reactions, both at the level of the oral cavity and the entire body. General redox balance disturbances do not coincide with salivary redox balance disturbances. Reduction in stimulated saliva secretion in AD patients reflects secretory dysfunction of the parotid glands., (© 2021. The Author(s).)

Chronic heart failure (HF) is an important clinical, social, and economic problem. A key role in HF progression is played by oxidative stress. Free oxygen radicals, formed under the conditions of hypoxia and reperfusion, participate in myocardial stunning and other forms of post-reperfusion damage. HF patients also suffer from disorders connected with saliva secretion. However, still little is known about the mechanisms that impair the secretory function of salivary glands in these patients. In the presented study, we were the first to compare the antioxidant barrier, protein glycoxidation, and nitrosative/nitrative stress in non-stimulated (non-stimulated whole saliva (NWS)) and stimulated (SWS) saliva of HF patients. The study included 50 HF patients with normal saliva (NS) secretion ( n = 27) and hyposalivation (HS) ( n = 23), as well as an age- and gender-matched control group ( n = 50). We demonstrated that, in NWS of HF patients with HS, the concentration of low-molecular-weight non-enzymatic antioxidants decreased (↓total polyphenols, ↓ascorbic acid, ↓reduced glutathione, ↓albumin) compared to HF patients with normal saliva (NS) secretion, as well as the control group (except albumin). We also observed increased content of protein glycoxidation products (↑dityrosine, ↑kynurenine, ↑glycophore) in NWS and SWS of HF patients with HS compared to healthy controls. Interestingly, the content of dityrosine, N-formylkynurenine, and glycophore in NWS was also significantly higher in HF patients with HS compared to those with NS secretion. The concentration of NO was considerably lower, while the levels of peroxynitrite and nitrotyrosine were significantly higher in NWS and SWS of HF subjects with HS compared to the controls. Salivary gland dysfunction occurs in patients with chronic HF with the submandibular salivary glands being the least efficient. Oxidative/nitrosative stress may be one of the mechanisms responsible for the impairment of salivary gland secretory function in HF patients.

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Mateusz Maciejczyk et al.)

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Anna Zalewska et al.)

This is the first study to assess the effect of N-acetylcysteine (NAC) on the mitochondrial respiratory system, as well as free radical production, glutathione metabolism, nitrosative stress, and apoptosis in the salivary gland mitochondria of rats with high-fat diet (HFD)-induced insulin resistance (IR). The study was conducted on male Wistar rats divided into four groups of 10 animals each: C (control, rats fed a standard diet containing 10.3% fat), C + NAC (rats fed a standard diet, receiving NAC intragastrically), HFD (rats fed a high-fat diet containing 59.8% fat), and HFD + NAC (rats fed HFD diet, receiving NAC intragastrically). We confirmed that 8 weeks of HFD induces systemic IR as well as disturbances in mitochondrial complexes of the parotid and submandibular glands of rats. NAC supplementation leads to a significant increase in the activity of complex I, II + III and cytochrome c oxidase (COX), and also reduces the ADP/ATP ratio compared to HFD rats. Furthermore, NAC reduces the hydrogen peroxide production/activity of pro-oxidant enzymes, increases the pool of mitochondrial glutathione, and prevents cytokine formation, apoptosis, and nitrosative damage to the mitochondria in both aforementioned salivary glands of HFD rats. To sum up, NAC supplementation enhances energy metabolism in the salivary glands of IR rats, and prevents inflammation, apoptosis, and nitrosative stress.

Oxidative stress plays a crucial role in the salivary gland dysfunction in insulin resistance; however, the cause of increased free radical formation in these conditions is still unknown. Therefore, the aim of the study was to investigate the effect of high-fat diet (HFD) on the mitochondrial respiratory system, prooxidant enzymes, ROS production, and nitrosative/oxidative stress in the submandibular and parotid glands of rats. The experiment was performed on male Wistar rats divided into two groups ( n = 10): control and HFD. The 8-week feeding of HFD affects glucose metabolism observed as significant increase in plasma glucose and insulin as well as HOMA-IR as compared to the control rats. The activity of mitochondrial Complex I and Complex II+III was significantly decreased in the parotid and submandibular glands of HFD rats. Mitochondrial cytochrome c oxidase (COX) activity and the hydrogen peroxide level were significantly increased in the parotid and submandibular glands of the HFD group as compared to those of the controls. HFD rats also showed significantly lower reduced glutathione (GSH) and reduced : oxidized glutathione (GSH : GSSG) ratio, as well as a higher GSSG level in the parotid glands of HFD rats. The activity of NADPH oxidase, xanthine oxidase, and levels of oxidative/nitrosative stress (malonaldehyde, nitric oxide, nitrotyrosine, and peroxynitrite) and inflammation/apoptosis (interleukin-1 β and caspase-3) biomarkers were statistically elevated in the HFD group in comparison to the controls. HFD impairs mitochondrial function in both types of salivary glands by enhancing ROS production, as well as stimulating inflammation and apoptosis. However, free radical production, protein nitration, and lipid peroxidation were more pronounced in the parotid glands of HFD rats.

Whey protein concentrate (WPC) is characterized by powerful antioxidant properties, but its effect on redox homeostasis of salivary glands of aging organisms is still unknown. In this study, we are the first to evaluate the antioxidant barrier of salivary glands of 14-month Wistar rats fed WPC-80. Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) as well as concentrations of reduced glutathione (GSH) are estimated in the submandibular and parotid glands of rats administered WPC-80 intragastrically for a period of 7 and 14 days. We demonstrate a significant increase in GSH, GPx and SOD in the salivary glands of rats fed WPC-80 for 14 days and a significant increase in TAS, GPx and SOD in the parotid glands of rats fed WPC-80 for 7 days compared to control rats. The beneficial effects of WPC-80 on salivary glands are also demonstrated by lower TOS and OSI in the parotid glands of rats fed WPC-80 compared to the submandibular glands. In summary, we demonstrate that WPC-80 improves redox homeostasis in salivary glands, particularly in the parotid glands of old rats.

Oxidative stress plays a crucial role in the salivary gland dysfunction in insulin resistance (IR). It is not surprising that new substances are constantly being sought that will protect against the harmful effects of IR in the oral cavity environment. The purpose of this study was to evaluate the effect of N-acetylcysteine (NAC) on oxidative stress and secretory function of salivary glands in a rat model of insulin resistance. Rats were divided into 4 groups: C-normal diet, C + NAC-normal diet + NAC, HFD-high-fat diet, and HFD + NAC. We have demonstrated that NAC elevated enzymatic (superoxide dismutase, catalase, and peroxidase) and nonenzymatic antioxidants (reduced glutathione (GSH) and total antioxidant capacity (TAS)) in the parotid glands of HFD + NAC rats, while in the submandibular glands increased only GSH and TAS levels. NAC protects against oxidative damage only in the parotid glands and increased stimulated salivary secretion; however, it does not increase the protein secretion in the both salivary glands. Summarizing, NAC supplementation prevents the decrease of stimulated saliva secretion, seen in the HFD rats affected. NAC improves the antioxidative capacity of the both glands and protects against oxidative damage to the parotid glands of IR rats.

Objective: Chronic high protein intake leads to an increase in reactive oxygen species (ROS) generation. However, there is no data on the impact of high-protein diet on the antioxidant barrier, oxidative stress and secretory function in the salivary glands of healthy individuals., Design: 16 male Wistar rats were randomly divided into 2 groups (n=8): normal protein (C) and high-protein diet (HP) for 8 weeks. Salivary antioxidants: peroxidase (Px), catalase (CAT), superoxide dismutase 1 (SOD 1), uric acid (UA), total antioxidant status (TAS), total oxidant status (TOS) and the oxidative stress index (OSI), as well as protein carbonyls (PC), 4-hydroxynonenal protein adduct (4-HNE protein adduct), 8-isoprostanes (8-isoP), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and protein content were determined in the salivary glands and plasma. Salivary unstimulated and stimulated flow rates were examined., Results: Parotid Px, TAS, UA, TOS, OSI, PC were significantly higher, the total protein content was statistically lower in the HP group as compared to the control. Submandibular UA, TOS, OSI, 8-isoP, 4-HNE-protein adduct, 8-OHdG were statistically elevated, SOD 1 and Px were significantly lower in the HP group as compared to the control rats. The unstimulated salivary flow rate was significantly depressed in the HP group as compared to the controls., Conclusions: Higher antioxidant capacity in the parotid glands of HP rats vs. control rats seems to be a response to a higher ROS formation. In the submandibular glands severe oxidative modification of almost all cellular components was observed. Administration of HP resulted in the weakening of the salivary gland function., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Diabetes is one of the most common metabolic diseases. Moreover, previous studies indicate that diabetes may cause changes in the salivary glands phenotype and in the composition of saliva itself. Therefore, the main objective of this study was to determine the effects of streptozotocin induced diabetes on lipid profile of the rat salivary glands., Methods: Male Wistar rats were divided into two groups: control and STZ-induced diabetes. At the end of the experiment all animals were sacrificed and samples of the parotid and submandibular salivary glands were excised. Major lipid fractions concentrations were determined by means of chromatography (TLC and GC)., Results: We observed a significant increase (∼3.5 fold) in the level of triacylglycerol in both the parotid and submandibular salivary glands of diabetic rats. The abovementioned changes were accompanied by significant, although less dramatic (i.e. from -60% to -90%), decrements in the levels of other lipid classes (phospholipids, free fatty acids and diacylglycerol)., Conclusions: In our study we have showed, presumably for the first time, that streptozotocin induced diabetes causes decrement in PH content with subsequent atrophy and malfunction in both parotid and submandibular salivary glands. Another novel finding of our research is that diabetic rats were characterized by an increased TG accumulation in both parotid and submandibular salivary glands. The later one could be a clinical manifestation of diabetes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Matrix metalloproteinases (MMPs) belong to a family of structurally related zinc-dependent proteolytic enzymes that are known to play a key role in the catabolic turnover of extracellular matrix (ECM) components. Research studies to date have indicated that MMPs regulate the activity of several non-ECM bioactive substrates, including growth factors, cytokines, chemokines and cell receptors, which determine the tissue microenvironment. Disruption of the balance between the concentration of active matalloproteinases and their inhibitors (TIMPs) may lead to pathological changes associated with uncontrolled ECM turnover, tissue remodeling, inflammatory response, cell growth and migration. This brief review presents some information on MMPs' role in inflammatory, metabolic and cancer abnormalities related to the salivary glands, as well as MMP-related aspects that lead to the formation of human dentinal caries lesions. In oral diseases, the most relevant biological fluid commonly used for diagnosing periodontal diseases is saliva. In diseased patients with significantly higher levels of MMPs in their saliva than healthy people, most extracellular matrix components undergo digestion to lower molecular weight forms. Conventional treatment successfully reduces the levels of MMPs inhibits the progressive breakdown of gingival and periodontal ligament collagens. Beside inflammatory abnormalities like Sjögren's syndrome (SS), a large group of disorders is comprised of cancers, most of them involving the parotid gland.

Objective: The aim of this study was to estimate the antioxidants barrier, and the oxidative stress in the salivary glands of rats in different periods of streptozotocin induced diabetes., Design: Rats were divided in: 4 control (C2/4/10/14) and 4 experimental (DM2/4/10/14) groups. Salivary glands were removed 2/4/10/14 weeks after streptozotocin injection. Peroxidase (Px), uric acid (UA), total antioxidant status (TAS), superoxide dismutases (SODs), catalase (CAT), malonylodialdehyde (MDA), advanced glycation end products (AGE) concentrations were examined., Results: TAS, Px were lower in the parotid diabetic glands throughout the whole experiment. TAS in the submandibular diabetic glands was lower in 2nd and 4th and higher in 14th week. Px in the submandibular diabetic glands was reduced in 4th and increased in 14th week. UA was lower in parotid, elevated in submandibular diabetic glands in 4th, 10th, 14th weeks. In the submandibular as compared to parotid glands an increase in TAS and UA was observed in 10th and 14th, Px in 14th week. In all periods, a significant increase in AGE was observed in both diabetic salivary glands. An increase in MDA was observed in the parotid diabetic glands in the 4th, 10th, 14th of the study. In the submandibular glands this increase was observed in the 2nd, 4th, 10th week, in the 14th week, the MDA level was significantly reduced in comparison to the control., Conclusion: The antioxidants of parotid glands are deficient throughout the whole experiment. In the last period submandibular glands copy with free radicals, becoming the main antioxidant's source., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: The aim of the present study was to evaluate the possibility of making use of the specific activity of N-acetyl-β-hexosaminidase, its isoenzymes and β-glucuronidase--potential indicators of salivary gland damage--in the detection of early onset of salivary gland impairment in RA, which is also demonstrated by xerostomia., Material/methods: For this purpose RA xerostomic salivary patients (unstimulated salivary flow >0.1 mL/min) were compared with RA xerostomic hyposalivary patients (unstimulated salivary flow ≤0.1 mL/min), RA patients without xerostomia (unstimulated salivary flow >0.1 mL/min) and generally healthy controls (unstimulated salivary flow >0.1 mL/min, without xerostomia). Salivary N-acetyl-β-hexosaminidase, its isoenzymes A and B, and β-glucuronidase specific activity were determined according to the Marciniak et al. method. The protein content in the unstimulated saliva was determined by the bicinchoninic acid method., Results: In xerostomic rheumatoid arthritis patients, the specific activity of salivary β-glucuronidase and isoenzyme A was significantly higher than in the healthy controls but the specific activity of salivary N-acetyl-β-hexosaminidase, its isoenzyme B and β-glucuronidase was significantly lower than in xerostomic hyposalivary rheumatoid arthritis patients., Conclusions: We suggest a simple, safe and cheap method for the determination of exoglycosidases as a useful tool for the diagnosis of early stages of salivary gland involvement in rheumatoid arthritis.

Ethanol diffuses rapidly into saliva during the drinking, and immediately after its salivary concentration is temporarily much higher than in plasma. Within 30 minutes, salivary ethanol concentration equilibrates with the plasma level, thus suggesting that ethanol easily penetrates the whole body, including oral cavity tissues and salivary glands. After alcohol intake, the level of acetaldehyde in saliva strikingly exceeds the level in systemic blood. From saliva, acetaldehyde and ethanol easily reach all local tissues. Damage to the oral tissues seems to be ascribed mostly to the action of acetaldehyde, although some acute effects depend on a direct action of ethanol and formation of reactive oxygen species (ROS) and fatty acid ethyl esters (FAEEs). It is known that the oral mucosal surface is the home of numerous normal flora microorganisms and is the portal of entry for the majority of pathogens. The oral cavity and salivary antimicrobial immune defense systems eliminate pathogens and prevent massive overgrowth of microorganisms. An oral defense system participate in the protection of not only oral tissues, but also in the protection of upper digestive and respiratory tracts, against a number of microbial pathogens. Saliva plays the role in the oral cavity lubrication, maintenance of mucosal and tooth integrity, esophageal physiology, digestion and gastric cytoprotection. As alcohol abuse affects the structure and function of oral cavity mucosa, salivary glands and saliva, the maintenance of oral and general health under normal conditions is seriously impaired during the drinking. The severe tissue damage occurs in particular when alcohol abuse coincides with smoking.

Introduction: Chronic kidney disease (CKD) is a systemic inflammatory disease that leads to multiple organ complications not only in the kidneys and the cardiovascular system, but also in the oral cavity. CKD children experience reduced saliva secretion (hyposalivation), which leads to increased incidence of dental caries and significant impairment of patients' quality of life. However, the causes of salivary gland dysfunction in children with CKD are unknown. The present study is the first to evaluate the inflammatory and anti-inflammatory profile in the saliva of children with CKD at different stages of renal failure with normal and reduced salivary gland function. Methods: Thirty children with CKD (age 9– 16) and thirty age- and gender-matched healthy children were classified for the study. Salivary inflammatory and anti-inflammatory profile were assayed using the multiplex ELISA assay. Results: We demonstrated statistically significant changes in salivary pro-inflammatory (↑TNF-α, ↓IL-7), anti-inflammatory (↑IL-10), Th1 (↑INF-γ, ↑IL-15), Th2 (↑IL-4, ↑IL-5, ↑IL-6, ↑IL-9) and Th17 (IL-17) cytokines as well as chemokines (↑MCP-1/CCL-2, ↑MIP-1α/CCL3, ↓MIP-1β/CCL4, ↓EOTAXIN/CCL11) and growth factors (↑G-CSF, ↑FGF) in unstimulated saliva of children with CKD compared to the controls. Although the evaluation of the salivary inflammatory profile does not indicate a particular dominance of any of the branches of the immune system, we observed a statistically significant increase in the concentration of all Th2 cytokines assayed. The multivariate regression analysis showed that the content of salivary cytokines, chemokines and growth factors depends on the secretory function of the salivary glands, ie, salivary flow, total protein concentration and amylase activity in the saliva. Salivary MIP-1α/CCL3 was the most effective to differentiate children with CKD and hyposalivation from patients with normal saliva secretion. Discussion: Inflammation is involved in salivary gland dysfunction in children with CKD, although further studies on in vitro and in vivo models are necessary to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is one of the leading causes of death worldwide. HF results not only in cardiovascular dysfunction, but also numerous pathologies in the oral cavity and salivary glands. The present study is the first to evaluate whether salivary inflammatory and anti-inflammatory factors may be related with the occurrence of hyposalivation in HF patients. We also evaluated the potential of salivary biomarkers in the diagnostics of HF. The study included 30 women with HF and 30 sex- and age-matched healthy controls. We demonstrated significantly higher levels of pro-inflammatory cytokines, anti-inflammatory cytokines, Th1, Th2, Th17, chemokines and growth factors in unstimulated saliva of HF patients compared to controls. However, the results do not indicate dominance of either branch of the immune response. The concentration of selected biomarkers is significantly higher in patients with HF and salivary gland dysfunction compared to patients with normal saliva secretion and healthy subjects (IL-1b, TNF-a, IL-7, IL-13, INF-g, IL-12, IL-15, IL-5, IL-6, IL-9, IL-17, MCP-1/CCL-2, EOTAXIN/CCL11, RANTES/CCL5, GM-CSF, VEGF, FGF basic, PDFG-BB). Multivariate regression analysis showed that the content of salivary cytokines, chemokines and growth factors is highly dependent on salivary gland function, i.e. salivary flow rate, total protein content and amylase activity. Using receiver operating characteristic (ROC) analysis, we showed that salivary TNF-a, INF-g, IL-12 and EOTAXIN/CCL11 differentiated patients with HF and hyposalivation with the highest sensitivity and specificity compared to patients with normal salivary secretion and controls. Interestingly, the content of some pro- and anti-inflammatory mediators in saliva significantly exceeds their concentration in plasma. In addition, salivary biomarker levels do not reflect their plasma content, which may suggest a different nature/severity of inflammatory changes at the central (blood) and local (salivary) levels. Although our study was purely observational, the significantly higher concentration of inflammatory parameters in saliva compared to plasma, as well as the lack of saliva-blood correlation, may suggest increased production/ secretion of these compounds in salivary cells of HF patients. ROC analysis did not confirm the diagnostic utility of salivary cytokines and chemokines in the differential diagnosis of HF patients. [ABSTRACT FROM AUTHOR]

Diabetes is considered a major public health problem affecting millions of individuals worldwide. Remarkably, scientific reports regarding salivary glands sphingolipid metabolism in diabetes are virtually non-existent. This is odd given the well-established link between the both in other tissues (e.g., skeletal muscles, liver) and the key role of these glands in oral health preservation. The aim of this paper is to examine sphingolipids metabolism in the salivary glands in (pre)diabetes (evoked by high fat diet feeding or streptozotocin). Wistar rats were allocated into three groups: control, HFD-, or STZ-diabetes. The content of major sphingolipid classes in the parotid (PSG) and submandibular (SMSG) glands was assessed via chromatography. Additionally, Western blot analyses were employed for the evaluation of key sphingolipid signaling pathway enzyme levels. No changes in ceramide content in the PSG were found, whereas an increase in ceramide concentration for SMSG of the STZ group was observed. This was accompanied by an elevation in SPT1 level. Probably also sphingomyelin hydrolysis was increased in the SMSG of the STZ-diabetic rats, since we observed a significant drop in the amount of SM. PSG and SMSG respond differently to (pre)diabetes, with clearer pattern presented by the later gland. An activation of sphingomyelin signaling pathway was observed in the course of STZ-diabetes, that is, metabolic condition with rapid onset/progression. Whereas, chronic HFD lead to an inhibition of sphingomyelin signaling pathway in the salivary glands (manifested in an inhibition of ceramide de novo synthesis and accumulation of S1P). [ABSTRACT FROM AUTHOR]

Still little is known about the role of oxidative stress (OS) in the pathogenesis of the salivary gland dysfunction in the course of insulin resistance (IR). To induce IR rats was fed with a high fat diet (HFD) during 8 weeks. Stimulated and non-stimulated salivary flow rate, total protein, as well as oxidative damage markers: 4-HNE protein adduct, 8-isoprostanes (8-isoP), 8-hydroxy-D-guanosine (8-OHdG), advanced oxidation protein product (AOPP), and protein carbonyls (PC) were determined in the plasma and submandibular and parotid glands of IR and control rats. We have shown a significant decrease (45%) of the stimulated salivary flow rate, and in the total protein concentration in the parotid (35%) and submandibular (10%) glands of HFD IR as compared to the control rats. The level of 4-HNE protein adduct (15%) and 8-isoP (20%) in the submandibular glands of IR rats as well as total level of 4-HNE protein adduct (39%), 8-isoP (27%), AOPP (25%), PC (32%), and 8-OHdG (18%) in the parotid glands of IR rats were significantly higher as compared to the control group. We showed no correlation between the assessed OS parameters in the plasma and salivary glands. However, the redox balance in both glands shifted toward the oxidative status, parotid glands of IR rats are exposed to greater intensity OS. Stimulated secretory ability and mechanisms involved in the synthesis/secretion of proteins in the salivary glands are depressed in the course of IR. Oxidative damage in the salivary glands arises independently from the general OS in the course of insulin resistance induced by a high fat diet. [ABSTRACT FROM AUTHOR]

In today’s world wrong nutritional habits together with a low level of physical activity have given rise to the development of obesity and its comorbidity, insulin resistance. More specifically, many researches indicate that lipids are vitally involved in the onset of a peripheral tissue (e.g., skeletal muscle, heart, and liver) insulin resistance. Moreover, it seems that diabetes can also induce changes in respect of lipid composition of both the salivary glands and saliva. However, judging by the number of research articles, the salivary glands lipid profile still has not been sufficiently explored. In the current study we aim to assess the changes in the main lipid fractions, namely, triacylglycerols, phospholipids, free fatty acids, and diacylglycerols, in the parotid and the submandibular salivary glands of rats exposed to a 5-week high fat diet regimen. We observed that the high caloric fat diet caused a significant change in the salivary glands lipid composition, especially with respect to PH and TG, but not DAG or FFAs, classes. The observed reduction in PH concentration is an interesting phenomenon frequently signifying the atrophy and malfunctions in the saliva secreting organs. On the other hand, the increased accumulation of TG in the glands may be an important clinical manifestation of metabolic syndrome and type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objective: There is no study evaluating the influence of morbid obesity and bariatric surgery on antioxidant/oxidant homeostasis of the unstimulated and stimulated human saliva.Materials and Methods: Salivary flow rate, total antioxidant status (TAS), total oxidant status (TOS), oxidative status index (OSI), the total amount of uric acid (UA), polyphenols (pPh), catalase (CAT), superoxide dismutase 2 (SOD2), specific activity of peroxidase (Px), as well as malondialdehyde (MDA), and advanced glycation end products (AGE) concentrations were determined in the unstimulated (UWS) and stimulated (SWS) whole saliva of patients with morbid obesity before and after bariatric surgery.Results: In both UWS and SWS, the total amount of TOS, OSI, SOD2, and MDA was statistically higher in patients with morbid obesity as compared to the healthy controls, as well as significantly lower in the patients treated surgically as compared to the obese patients. The median values of the total amount of TAS, CAT, UA, pPh, and specific activity of Px were significantly reduced in UWS and SWS in patients with morbid obesity as compared to the control group and also statistically elevated in patients after bariatric surgery as compared to the patients with morbid obesity.Conclusions: In morbid obesity, reduced unstimulated and stimulated salivary flow can be observed. Bariatric surgery restored only unstimulated salivary flow to normal values. Disturbances in oxidant/antioxidant homeostasis may be observed in UWS and SWS of obese patients before and after treatment. [ABSTRACT FROM AUTHOR]

Background However, there are some informations on the salivary glands involvement in systemic sclerosis, and there is a lack of any data about salivary glands function depending on systemic sclerosis subsets. Methods The unstimulated and stimulated salivary flow, the activity of peroxidase, the total amount of lactoferrin, lysozyme and s Ig A were determined in two subgroups of systemic sclerosis and healthy controls. Results In the unstimulated saliva of both patients groups, the salivary flow, the output of total protein and peroxidase activity were significantly lower; the total: s Ig A and lactoferrin were significantly higher as compared with the control. In the stimulated saliva of the patients with limited form, the total lysozyme and peroxidase activity were significantly higher than in the control. In the stimulated saliva of the patients with diffused form, the salivary flow was significantly lower and the total s Ig A and peroxidase activity were significantly higher than in the control. Conclusion Systemic sclerosis regardless of its subset affects salivary defense system of human unstimulated and stimulated saliva. Patients with the limited form experience the same impairment of the submandibular glands function as compared with patients with the diffused form. Only patients with the diffused form are deficient in respect of stimulated saliva secretion; the parotid glands of the patients with the limited form have a good secretory capacity in comparison with the healthy control. [ABSTRACT FROM AUTHOR]

Introduction: As exoglycosidases have been described as potential markers of salivary gland pathology, we decided to check the possibility of the use of these enzymes in the detection of salivary gland involvement in gestational diabetes. Materials and methods: For this purpose diabetic pregnant women were compared to pregnant and non-pregnant healthy women. The activities of total HEX as well as GLU in the saliva were determined in duplicate according to Marciniak et al. The activities of GAL, FUC, and MAN in the saliva were determined in duplicate according to Zwierz et al. Results: It was found that the specific activities of exoglycosidases in the saliva of diabetic pregnant women significantly increased in comparison to healthy pregnant and non-pregnant women. Conclusion: Increased specific activity of exoglycosidases suggests that gestational diabetes provokes structural/ functional alterations in salivary glands and changes in the salivary glycoconjugates metabolism [ABSTRACT FROM AUTHOR]

This is the first study to assess, comprehensively, the oral health status; salivary glands' function and enzymatic and non-enzymatic antioxidant defense; and oxidative damage to proteins and lipids in the non-stimulated (NWS) and stimulated (SWS) whole saliva of stroke patients. The study included 30 patients in the subacute phase of the stroke and an age and gender-matched control group. We showed that the activity of antioxidant enzymes (catalase and salivary peroxidase) was significantly higher in both NWS and SWS of stroke patients, similarly to uric acid concentration. However, in the study group, the reduced glutathione (GSH) concentration in SWS decreased. The contents of protein glycooxidation products (advanced glycation end products (AGE) and protein oxidation products (AOPP)) and lipid hydroperoxides were significantly higher in NWS and SWS of stroke patients. In the study group there was also a decrease in stimulated saliva secretion and total protein content. Interestingly, products of protein and lipid oxidation correlate negatively with SWS flow. The ROC analysis showed that salivary GSH with 100% specificity and 100% sensitivity differentiates the analyzed groups (AUC = 1.0). To sum up, in subacute stroke patients there are redox imbalances and oxidative damage to proteins and lipids in non-stimulated and stimulated saliva. Stroke patients also suffer from salivary gland dysfunction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the rate of reactive oxygen species (ROS) production, antioxidant barrier, and oxidative damage in non-stimulated (NWS) and stimulated (SWS) saliva as well as plasma/erythrocytes of 50 patients with chronic heart failure (HF) divided into the two subgroups: NYHA II (33 patients) and NYHA III (17 patients). The activity of superoxide dismutase and catalase was statistically increased in NWS of HF patients as compared to healthy controls. The free radical formation, total oxidant status, level of uric acid, advanced glycation end products (AGE), advanced oxidation protein products and malondialdehyde was significantly elevated in NWS, SWS, and plasma of NYHA III patients as compared to NYHA II and controls. We were the first to demonstrate that with the progression of HF, disturbances of enzymatic and non-enzymatic antioxidant defense, and oxidative damage to proteins and lipids occur at both central (plasma/erythrocytes) and local (saliva) levels. In the study group, we also observed a decrease in saliva secretion, total salivary protein and salivary amylase activity compared to age- and gender-matched control group, which indicates secretory dysfunction of salivary glands in patients with HF. Salivary AGE may be a potential biomarker in differential diagnosis of HF. [ABSTRACT FROM AUTHOR]

Psoriasis is the most common inflammatory skin disease, characterized by the release of proinflammatory cytokines from lymphocytes, keratinocytes, and dendritic cells. Although psoriasis is considered an immune-mediated inflammatory disease, its effect on secretory activity of salivary glands and quantitative composition of saliva is still unknown. The aim of this study was to evaluate the secretion of saliva as well as several selected inflammation and nitrosative stress biomarkers in unstimulated and stimulated saliva as well as plasma of psoriasis patients. We demonstrated that, with progressing severity and duration of the disease, the secretory function of the parotid and submandibular salivary glands is lost, which is manifested as decreased unstimulated and stimulated saliva secretion and reduced salivary amylase activity and total protein concentration. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and interferon-gamma (INF-γ) were significantly higher, whereas interleukin-10 (IL-10) content was considerably lower in unstimulated and stimulated saliva of patients with psoriasis compared to the controls, and the changes increased with the disease duration. Similarly, we observed that the intensity of nitrosative stress in the salivary glands of psoriasis patients depended on the duration of the disease. By means of receiver operating characteristic (ROC) analysis, we showed that the evaluation of nitric oxide (NO), nitrotyrosine, and IL-2 concentration in non-stimulated saliva with high sensitivity and specificity differentiated psoriasis patients on the basis of the rate of saliva secretion (normal salivation vs. hyposalivation). In summary, the dysfunction of salivary glands in psoriasis patients is caused by inflammation and nitrosative stress. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This is the first study to investigate the relationship between ceramides, the mitochondrial respiratory system, oxidative stress, inflammation, and apoptosis in the submandibular gland mitochondria of mice with insulin resistance (IR). The experiment was conducted on 20 male C57BL/6 mice divided into two equal groups: animals fed a high-fat diet (HFD; 60 kcal% fat) and animals fed a standard diet (10 kcal% fat). We have shown that feeding mice HFD induces systemic IR. We noticed that HFD feeding was accompanied by a significant increase in ceramide production (C18 1Cer, C18 Cer, C22 Cer, C24 1Cer, C24 Cer), higher activity of pro-oxidant enzymes (NADPH oxidase and xanthine oxidase), and weakened functioning of mitochondrial complexes in the submandibular glands of IR mice. In this group, we also observed a decrease in catalase and peroxidase activities, glutathione concentration, redox status, increased concentration of protein (advanced glycation end products, advanced oxidation protein products) and lipid (malondialdehyde, lipid hydroperoxide) peroxidation products, and enhanced production of tumor necrosis factor alpha (TNFα) and interleukin 2 (IL-2) as well as pro-apoptotic Bax in the submandibular gland mitochondria. In summary, HFD impairs salivary redox homeostasis and is responsible for enhanced oxidative damage and apoptosis in the submandibular gland mitochondria. The accumulation of some ceramides could boost free radical formation by affecting pro-oxidant enzymes and the mitochondrial respiratory chain. [ABSTRACT FROM AUTHOR]

A high-sucrose diet (HSD) is widely known for its cariogenic effects and promotion of obesity, insulin resistance, type 2 diabetes, and cancer. However, the impact of the HSD diet on the salivary gland function as well as the level of salivary oxidative stress is still unknown and requires evaluation. Our study is the first to determine both redox balance and oxidative injury in the parotid and submandibular glands of rats fed the HSD diet compared to the control group. We have demonstrated that uric acid concentration and the activity of superoxide dismutase and peroxidase varied significantly in both the submandibular and parotid glands of HSD rats vs. the control group. However, enhanced oxidative damage to proteins, lipids, and DNA (increase in advanced glycation end products, advanced oxidation protein products, 4-hydroxynonenal, and 8-hydroxy-2'-deoxyguanosine) was observed only in the parotid glands of HSD rats. Moreover, the HSD diet also reduced the total protein content and amylase activity in both types of salivary glands and decreased the stimulated salivary flow rate. To sum up, an HSD diet reduces salivary gland function and disturbs the redox balance of the parotid as well as submandibular salivary glands. However, the parotid glands are more vulnerable to both antioxidant disturbances and oxidative damage. [ABSTRACT FROM AUTHOR]

Whey protein concentrate (WPC) is characterized by powerful antioxidant properties, but its effect on redox homeostasis of salivary glands of aging organisms is still unknown. In this study, we are the first to evaluate the antioxidant barrier of salivary glands of 14-month Wistar rats fed WPC-80. Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) as well as concentrations of reduced glutathione (GSH) are estimated in the submandibular and parotid glands of rats administered WPC-80 intragastrically for a period of 7 and 14 days. We demonstrate a significant increase in GSH, GPx and SOD in the salivary glands of rats fed WPC-80 for 14 days and a significant increase in TAS, GPx and SOD in the parotid glands of rats fed WPC-80 for 7 days compared to control rats. The beneficial effects of WPC-80 on salivary glands are also demonstrated by lower TOS and OSI in the parotid glands of rats fed WPC-80 compared to the submandibular glands. In summary, we demonstrate that WPC-80 improves redox homeostasis in salivary glands, particularly in the parotid glands of old rats. [ABSTRACT FROM AUTHOR]

Increasing attention to the importance of saliva testing is not surprising because smoking and alcohol drinking act synergistically on oral tissues, and their metabolite levels, e.g., acetaldehyde, are much higher in saliva than in blood. The activity of salivary alcohol dehydrogenase (ADH) comes from oral microbiota, mucosa, and salivary glands. The purpose of this study was to investigate the involvement of ADH in the oral health pathology of smoking (AS) and non-smoking (ANS) alcohol-dependent males. The results indicated that the AS group had a more significant and longer duration (until the 30th day of alcohol abstinence) decrease in ADH activity and output than the ANS group (until the 15th day of alcohol abstinence) compared to controls (social drinkers; C). The decreased salivary flow (SF) in alcoholics was observed longer in the ANS group (until the 30th day of alcohol abstinence), whereas in the AS group SF normalized at the 15th day, probably due to the irritating effect of tobacco smoke on the oral mucosa. Because saliva was centrifuged to remove cells and debris (including microbial cells), the detected salivary ADH activity was derived from salivary glands and/or oral mucosa. A more profound and longer decrease in ADH activity/output in smoking than non-smoking alcoholics was likely due to the damaged salivary glands and/or oral mucosa, caused by the synergistic effect of alcohol drinking and smoking. The lower values of salivary ADH in smoking than non-smoking alcoholics might also be partly due to the reversed/inhibited ADH reaction by high levels of accumulated acetaldehyde. [ABSTRACT FROM AUTHOR]