α-Lipoic Acid Supplementation Salivary Glands in the Hyperglycaemic Rats.

BACKGROUND/AIMS: The aim of the present study was to investigate whether α-lipoic acid (ALA) could reverse/prevent high fat diet (HFD) -induced salivary gland dysfunction and oxidative damage in the salivary glands of rats, and strengthen their antioxidant defense. METHODS: The enzymatic and non-enzymatic antioxidants as well as their redox status, oxidative damage products and salivary flow rate were investigated in the parotid (PG) and submandibular (SMG) glands of Wistar rats exposed to a high-fat diet and then supplemented with ALA for a period of 4 weeks. The rats in the study were divided into 4 groups of 10 animals each: C (control), HFD,C + ALA, HFD + ALA. RESULTS: The HFD + ALA group in comparison to the HFD group showed normalization of the activity of antioxidant enzymes to the levels observed in the C group only in the case of the SMG. Additionally, ALA supplementation was more effective in reducing the value of oxidative damage products in the PG compared to the SMG. ALA supplementation in the HFD group was not able to restore the disturbed total antioxidant capacity (TAC) of the salivary glands to the level observed in the C group. In the group of HFD + ALA rats, both unstimulated and stimulated salivation and the protein concentration in the SMG did not differ significantly from the parameters recorded in the group fed with HFD. CONCLUSION: ALA supplementation by rats fed the HFD diet prevents/reverses oxidative damage in the PG to a greater extent than in the SMG and is unable to completely restore disturbed TAC to the levels seen in C rats. Moreover, we observed that ALA supplementation did not improve the impaired secretory function of the salivary glands.

Effect of streptozotocin-induced diabetes on lipids metabolism in the salivary glands.

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.

Impact of morbid obesity and bariatric surgery on antioxidant/oxidant balance of the unstimulated and stimulated human saliva.

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.

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

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.

Antioxidant Defense, Oxidative Modification, and Salivary Gland Function in an Early Phase of Cerulein Pancreatitis.

Acute pancreatitis (AP) is a multifactorial disease characterized by necroinflammatory changes of the pancreas. Our study is the first study which evaluated the relationship between the free radical production, enzymatic and nonenzymatic antioxidants, oxidative damage, and secretory function of the salivary glands of AP rats. Male Wistar rats were divided equally into 2 groups: control (n = 9) and AP (n = 9). AP was induced by intraperitoneal injection with cerulein and confirmed by higher serum amylase and lipase. We have demonstrated that the superoxide dismutase and glutathione reductase activities, as well as reduced glutathione concentration, were significantly decreased in both the parotid and submandibular glands of AP rats as compared to the control rats. The production of free radicals evidenced as dichlorodihydrofluorescein assay and the activity of NADPH oxidase and xanthine oxidase and IL-1ß concentration were significantly higher in the parotid and submandibular glands of AP rats compared to the controls. In AP rats, we also showed a statistical increase in oxidation modification products (advanced glycation end products and advanced oxidation protein products), salivary amylase activity, and significant decrease in the total protein content. However, we did not show apoptosis and any morphological changes in the histological examination of the salivary glands of AP rats. To sum up, cerulein-induced AP intensifies production of oxygen free radicals, impairs the redox balance of the salivary glands, and is responsible for higher oxidative damage to these glands. Interestingly, oxidative modification of proteins and dysfunction of the antioxidant barrier are more pronounced in the submandibular glands of AP rats.

Effect of N-Acetylcysteine on Antioxidant Defense, Oxidative Modification, and Salivary Gland Function in a Rat Model of Insulin Resistance.

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.

Eight-Week Consumption of High-Sucrose Diet Has a Pro-Oxidant Effect and Alters the Function of the Salivary Glands of Rats.

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.

Salivary lipids: A review.

Saliva is produced by both large and small salivary glands and may be considered one of the most important factors influencing the behavior of oral cavity homeostasis. Secretion of saliva plays an important role in numerous significant biological processes. Saliva facilitates chewing and bolus formation as well as performs protective functions and determines the buffering and antibacterial prosperities of the oral environment. Salivary lipids appear to be a very important component of saliva, as their qualitative and quantitative composition can be changed in various pathological states and human diseases. It has been shown that disturbances in salivary lipid homeostasis are involved in periodontal diseases as well as various systemic disorders (e.g. cystic fibrosis, diabetes and Sjögren's syndrome). However, little is known about the role and composition of salivary lipids and their interaction with other important ingredients of human saliva, including proteins, glycoproteins and salivary mucins. The purpose of this review paper is to present the latest knowledge on salivary lipids in healthy conditions and in oral and systemic diseases.

Oxidative Modification in the Salivary Glands of High Fat-Diet Induced Insulin Resistant Rats.

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.

Insulin Resistance and Obesity Affect Lipid Profile in the Salivary Glands.

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.

Antioxidant profile, carbonyl and lipid oxidation markers in the parotid and submandibular glands of rats in different periods of streptozotocin induced diabetes.

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.