Secretory Function Of Salivary Glands Research Articles

Salivary Gland Dysfunction in Patients with Chronic Heart Failure Is Aggravated by Nitrosative Stress, as Well as Oxidation and Glycation of Proteins.

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.

Salivary Gland Function, Antioxidant Defence and Oxidative Damage in the Saliva of Patients with Breast Cancer: Does the BRCA1 Mutation Disturb the Salivary Redox Profile?

Oxidative stress plays a key role in breast cancer progression. However, little is still known about the relationship between the BRCA1 mutation, the incidence of breast cancer and oral homeostasis. This is the first study to evaluate the secretory function of salivary glands, biomarkers of redox balance, and oxidative damage to proteins and lipids in the saliva of subjects with the BRCA1 mutation. Ninety eight women were enrolled in the study and allocated to four groups based on molecular DNA testing: generally healthy patients without the BRCA1 mutation, patients with breast cancer but without the BRCA1 mutation, generally healthy patients with the BRCA1 mutation, and patients with both breast cancer and the BRCA1 mutation. We demonstrated that saliva from breast cancer patients with the BRCA1 mutation is characterized by enhanced antioxidant capacity and a higher degree of oxidative damage to proteins and lipids. The BRCA1 mutation can cause a predisposition to early salivary gland dysfunction, both in patients with breast cancer and in healthy individuals, leading to a decrease in salivary proteins. Using cluster analysis, we showed that salivary peroxidase, advanced glycation end-products (AGE), total antioxidant status (TAS) and malondialdehyde (MDA) may have particular clinical significance in non-invasive diagnostics of breast cancer.

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.

The method of assessment of salivary glands secretory function

Aim. To develop a method for the assessment of the secretory function of salivary glands. Methods. BK-300.1 («MASSA-K», Russia) weighting machine (presicion ±0,01 g), two standard cotton swabs and two absorbent dental pads «Dry Tips» («Mölnlycke Health Care», Sweden) were used for the assessment of the secretory function of salivary glands. Each absorbent pad and cotton swabs were weighted before the procedure. The examination was performed at morning hours on a fasting patient seated on a dentist’s chair without salivation stimulation. Absorbent pads were placed on the buccal mucosa with parotid orifice at the centre of the pad. Absorbent pads and cotton swabs soaked with saliva were re-weighted after 5 minutes. The examination was repeated thrice at different visits, the mean weight of saliva from major salivary glands was calculated. Salivary function of submandibular and sublingual salivary glands was also assessed. Saliva weight was assessed for each parotid gland separately. Results. The advantages of the offered method are: ease of use, opportunity to assess each parotid, submandibular and sublingual gland separately, express evaluation, good tolerance. Conclusion. The developed method allows to get the precise result and to assess the secretory function of salivary glands accurately.

Radioprotective Effect of Lidocaine on Neurotransmitter Agonist-Induced Secretion in Irradiated Salivary Glands

BackgroundPreviously we verified the radioprotective effect of lidocaine on the function and ultrastructure of salivary glands in rabbits. However, the underlying mechanism of lidocaine's radioprotective effect is unknown. We hypothesized that lidocaine, as a membrane stabilization agent, has a protective effect on intracellular neuroreceptor-mediated signaling and hence can help preserve the secretory function of salivary glands during radiotherapy.Methods and MaterialsRabbits were irradiated with or without pretreatment with lidocaine before receiving fractionated radiation to a total dose of 35 Gy. Sialoscintigraphy and saliva total protein assay were performed before radiation and 1 week after the last radiation fraction. Isolated salivary gland acini were stimulated with either carbachol or adrenaline. Ca2+ influx in response to the stimulation with these agonists was measured using laser scanning confocal microscopy.ResultsThe uptake of activity and the excretion fraction of the parotid glands were significantly reduced after radiation, but lidocaine had a protective effect. Saliva total protein concentration was not altered after radiation. For isolated acini, Ca2+ influx in response to stimulation with carbachol, but not adrenaline, was impaired after irradiation; lidocaine pretreatment attenuated this effect.ConclusionsLidocaine has a radioprotective effect on the capacity of muscarinic agonist-induced water secretion in irradiated salivary glands.

Unilateral maxillary molar extraction influences AQP5 expression and distribution in the rat submandibular salivary gland

ObjectiveMastication has been regarded as a crucial factor for maintaining the morphology and function of secretion in salivary glands. Although it is known that occlusion affects mastication, the detailed process for how occlusal changes affect the secretory function of salivary glands is still unknown. Aquaporin 5 (AQP5) is a membrane protein that forms water channels, and plays an important role in water transport. In this study, we investigated the structural changes and alterations in the expression and distribution of AQP5 in the rat submandibular salivary gland (SMG) under occlusal hypofunction after unilateral molar extraction. MethodsSeven-week-old male Wistar rats (n=36) were used in the study. In the experimental group, all of the right maxillary molars were extracted. Rats with no molar extraction were used as the control group. The rats were euthanized at 7, 14 or 28 days after the procedure, and the right SMGs were isolated and subjected to histological analyses. The expression and distribution of AQP5 were detected by immunohistochemistry. ResultsMorphological analyses revealed hypertrophic changes in the acinar cells in the experimental group. Immunohistochemical staining of AQP5 was detected in the apical membrane (APM) and intercellular secretory canaliculi of acinar cells in both groups. On the other hand, the AQP5 expression in the APM and intercellular secretory canaliculi of acinar cells was less prominent in the experimental group than in the control group. ConclusionsThe present findings suggest that unilateral molar extraction has significant influences on the function of water transport in the rat SMG.

The Effect of Low-Level Laser Therapy on Salivary Glands in Patients with Xerostomia

The aim of this study was to investigate the effect of low-level laser irradiation on the secretory function of salivary glands in 34 patients with xerostomia (dry mouth). Xerostomia, a common complaint of oral dryness within the elderly population, is caused by a reduction in normal salivary secretion due to different causes. Treatment is aimed at increasing salivary flow, although in most cases it remains palliative. In this study, laser light from a pulsed Ga-As laser operating at 904 nm was applied bilaterally on each salivary gland area: extraorally on the parotid and submandibular gland areas and intraorally on the sublingual gland area. The operational probe distance from the irradiated area was 0.5 cm resulting in an irradiance of 246 mW/cm(2). The exposure time was 120 sec per daily treatment during 10 consecutive days. The average energy density per exposure was 29.5 J/cm(2). The control group consisted of 16 patients who were treated with 15 mL of a 2% citric acid solution applied as a mouth rinse for 30 sec. The average difference in the amount of salivation (dQ-sal, mL/min) before and after laser therapy increased linearly from dQ-sal = 0.05 mL/min on the first day, up to dQ-sal = 0.13 mL/min on the last (10th) day of therapy. In the control group, the average dQ-sal initially demonstrated a gradual increase, with a reversal of the trend toward the end of the therapy period and eventually yielding no correlation between the duration of therapy and dQ-sal. The results of our study indicate that the effects of low-level laser therapy on salivary glands are not only stimulating, but also regenerative to a degree since the glandular response to the same amount of applied laser energy increased linearly over time.

Sympathetic and parasympathetic interaction in vascular and secretory control of salivary glands in anaesthetised dogs

The present study was undertaken to examine sympathetic–parasympathetic interactions in the regulation of salivary gland function, with special reference to the possible role of the sympathetic cotransmitter neuropeptide Y (NPY). In dogs anaesthetised with pentobarbitone, electrical stimulation of the parasympathetic nerve to the submandibular gland evoked an increase in glandular blood flow and salivary secretion. Sympathetic nerve stimulation evoked a significant prolonged attenuation of vasodilator and secretory responses to subsequent parasympathetic stimulation. This attenuation was not significantly altered by α- and β-adrenoceptor blockade. Systemic administration of the sympathetic cotransmitter, NPY, mimicked the effect of the sympathetic stimulation by significantly attenuating vasodilatation and salivary secretion. The NPY Y 1 receptor agonist, [Leu 31, Pro 34]NPY and the specific NPY Y 2 receptor agonist N-acetyl[Leu 28, Leu 31]NPY 24–36 both significantly attenuated the vasodilatation and salivary secretion evoked by stimulation of the parasympathetic nerve. The NPY Y 1 receptor antagonist, GR231118 significantly antagonised the attenuation of vasodilatation caused by both sympathetic stimulation and the NPY Y 1 receptor agonist. GR231118 also inhibited the pressor response of NPY. Intra-arterial injection of methacholine and stimulation of the parasympathetic nerve both caused local vasodilatation in the gland which was significantly attenuated by pretreatment with sympathetic stimulation or the NPY Y 1 agonist. The NPY Y 2-specific agonist did not attenuate methacholine-induced vasodilatation but did attenuate vasodilatation evoked by parasympathetic stimulation. The results indicate that NPY as a sympathetic cotransmitter may have a role in the regulation of vascular secretory function of salivary glands.

Effect of sympathectomy on isoproterenol-induced expression of the cysteine proteinase inhibitor gene, cystatin S, in rat submandibular glands

The autonomic nervous system regulates the secretory function of salivary glands. The volume, rate of secretion and composition of saliva are regulated by both sympathetic ( α 1-, α 2and β 1-adrenergic) and parasympathetic (muscarinic and cholinergic) receptor systems. The rat cystatin S gene, a member of family 2 of the cysteine proteinase inhibitor superfamily, has a very defined pattern of expression during the postnatal development of the rat submandibular gland. Its expression is not detected in the fetus or in rats up to three weeks of age. After this time, the amount of cystatin S mRNA increases, reaching a conspicuously high concentration at 28 days, and then it declines to a barely detectable level at 32 days of age; cystatin S mRNA is not detectable in the glands of adult animals. However, the β-adrenoreceptor agonist isoproterenol (IPR) induces high concentrations of cystatin S mRNA in the submandibular gland in vivo. This paper reports experiments analysing the participation of the sympathetic nervous system in the IPR-induced expression of the cystatin S gene. Sympathetic denervation (unilateral and bilateral) by removing the superior cervical ganglion 14 days before a single injection of IPR reduced the expression of the cystatin S gene. Chemical denervation by reserpine (a drug that depletes neurotransmitters in sympathetic nerve terminals) also reduced IPR-induced expression of the gene. Morphological analyses of sympathectomized and reserpine-treated glands showed that the structure of the gland was similar to that of glands of intact animals and to those not treated with reserpine. The hypertrophic response to IPR was less obvious in the sympathectomized glands, but was similar in reserpine treated animals. Collectively, these data suggest that even in the presence of a functional β 1-adrenergic receptor pathway, factor(s) from the sympathetic nervous system may be required for IPR-induced expression of the cystatin S gene.

Esophagoprotective potential of cisapride. An additional benefit for gastroesophageal reflux disease.

Cisapride is a novel prokinetic agent that releases acetylcholine at the level of the myenteric plexus. Acetylcholine also plays a role in the secretory function of salivary glands evoked by intraesophagal mechanical and chemical stimulation, mediated through the esophagosalivary reflex. The impact, however, of cisapride on salivary protective components mediated by esophagosalivary reflex remains unknown. Therefore, we have studied salivary pH, bicarbonate, nonbicarbonate, glycoconjugate, protein, EGF, TGF-alpha, and PGE2 before and after the administration of cisapride. The study was conducted in 20 asymptomatic volunteers (9 women and 11 men, mean age 36, range 26-52). Salivary secretions were collected under basal conditions and during masticatory, mechanical, and chemical stimulation before and after four days of cisapride administration (10 or 20 mg four times a day). Cisapride administration resulted in a 45% increase in salivary volume during the basal condition (P < 0.01), a 32% increase during mastication (P < 0.05), a 53% increase during mechanical (P < 0.05), and a 51% increase during chemical (P < 0.01) stimulation. Cisapride administration resulted also in a significant increase in salivary protein output (P < 0.05), salivary bicarbonate (P < 0.05), and nonbicarbonate buffers (P < 0.05), and salivary EGF (P < 0.05). Salivary glycoconjugate significantly increased only during mechanical stimulation with the catheter and at the end of the esophageal perfusion procedure (P < 0.05). Although a similar trend was also recorded during the analysis of salivary PGE2, this difference did not reach statistical significance. Salivary pH and TGF-alpha before and after cisapride administration remained unchanged. The stimulatory impact of cisapride on salivary volume and inorganic (bicarbonate and nonbicarbonate buffers) and organic (protein, glycoconjugate, and EGF) protective components would benefit patients with GERD and would also be potential therapy for xerostomia.