The Biology And Chemistry of Saliva
Saliva
Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivaryglands in the mouth . In humans, saliva iser 99.5% water plus electolytess, mucus , white blood cells, epithelial cells (from which DNA can be extracted), enzymes (such as amylase and lipase), antimicrobial agents such as secretory IgA, and lysosomes.
The enzymes found in saliva are essential in beginning the process of digestion of dietary starches and fats. These enzymes also play a role in breaking down food particles entrapped within dental crevices, thus protecting teeth from bacterial decay. Saliva also performs a lubricating function, wetting food and permitting the initiation of swallowing, and protecting the oral mucosa from drying out.
Various animal species have special uses for saliva that go beyond predigestion. Some swifts use their gummy saliva to build nests. Aerodramusnests form the basis of bird’s nest soup, Cobras, vipers, and certain other members of the venom clade hunt with venomous saliva injected by fangs. Some caterpillars produce silk fibre from silk proteins stored in modified salivary glands.
Composition
Produced in salivary glands, human saliva comprises 99.5% water, but also contains many important substances, including electrolytes, mucus, antibacterial compounds and various enzymes.
Production of Saliva
The production of saliva is stimulated both by the sympathetic nervous system and the parasympathetic.
The saliva stimulated by sympathetic innervation is thicker, and saliva stimulated parasympathetically is more fluid-like.
Sympathetic stimulation of saliva is to facilitate respiration , whereas parasympathetic stimulation is to facilitate digestion .
Parasympathetic stimulation leads to acetylcholine (ACh) release onto the salivary acinar cells. ACh binds to muscarinic receptors, specifically M3, and causes an increased intracellular calcium ion concentration (through the IP3/DAG second messenger system). Increased calcium causes vesicles within the cells to fuse with the apical cell membrane leading to secretion. ACh also causes the salivary gland to release kallikrein, an enzyme that convertskininogen to lysyl-bradykinin. Lysyl-bradykinin acts upon blood vessels and capillaries of the salivary gland to generate vasodilation and increased capillary permeability, respectively. The resulting increased blood flow to the acini allows the production of more saliva. In addition, substance p can bind to TachykininNK-1 receptors leading to increased intracellular calcium concentrations and subsequently increased saliva secretion. Lastly, both parasympathetic and sympathetic nervous stimulation can lead to myoepithelium contraction which causes the expulsion of secretions from the secretory acinus into the ducts and eventually to the oral cavity.
Sympathetic stimulation results in the release of norepinephrine. Norepinephrine binding to a-adrenergic receptors will cause an increase in intracellular calcium levels leading to more fluid vs. protein secretion. If norepinephrine binds β-adrenergic receptors, it will result in more protein or enzyme secretion vs. fluid secretion. Stimulation by norepinephrine initially decreases blood flow to the salivary glands due to constriction of blood vessels but this effect is overtaken by vasodilation caused by various local vasodilators.
Saliva production may also be pharmacologically stimulated by the so-called sialagogues. It can also be suppressed by the so-called antisialagogues.
Behaviour that Stimulate Saliva
Spitting is the act of forcibly ejecting saliva or other substances from the mouth. In many parts of the world, it is considered rude and a social taboo, and has even been outlawed in many countries. In Western countries, for example, it has often been outlawed for reasons of public decency and attempting to reduce the spread of disease; however, these laws are often not strictly enforced. In Singapore, the fine for spitting may be as high as SGD$2,000 for multiple offenses, and one can even be arrested. In some other parts of the world, such as in China, expectoration is more socially acceptable (even if officially disapproved of or illegal), and spittoons are still a common appearance in some cultures. Some animals, even humans in some cases, use spitting as an automatic defensive maneuver. Camels are well known for doing this, though most domestic camels are trained not to.
Because saliva can contain large amounts of virus copies in infected individuals (for example, in people infected with (SARS-CoV-2 )spitting in public places can pose a health hazard to the public.
Glue to construct Bird’s nests
Many birds in the swift family, Apodidae, produce a viscous saliva during nesting season to glue together materials to construct a nest. Two species of swifts in the genus Aerodramus build their nests using only their saliva, the base for bird’s nest soup.
Wound Licking
A common belief is that saliva contained in the mouth has natural disinfectants, which leads people to believe it is beneficial to “lick their wound”. Researchers at the University of Florida at Gainesville have discovered a protein called nerve growth factor (NGF) in the saliva of mice. Wounds doused with NGF healed twice as fast as untreated and unlicked wounds; therefore, saliva can help to heal wounds in some species. NGF has not been found in human saliva; however, researchers find human saliva contains such antibacterial agents as secretory mucin , IgA, lactoferrin, lysozyme and peroxidase.
Classical conditioning
In Pavlov’s experiment, dogs were conditioned to salivate in response to a ringing bell, this stimulus is associated with a meal or hunger. Salivary secretion is also associated with nausea.
Saliva is usually formed in the mouth through an act called gleeking, which can be voluntary or involuntary.
Making alcoholic beverages
Some old cultures chewed grains to produce alcoholic beverages, such as chicha, kasiri or sake.
functions of Saliva
1. Immune functions
The components like lysozyme, lactoferrin, salivary peroxidase, myeloperoxidase, and thiocyanate concentrations act as a defense mechanism in the whole saliva. The natural defense properties of salivary secretions through clinical modalities such as the development of (1) diagnostic reagents and tests for local and systemic disease, (2) artificial salivas for the treatment of salivary dysfunction, and (3) topical vaccines to combat against oral diseases. Salivary mucins are well recognized as an important factor in the preservation of the health of the oral cavity and are of significance to the processes occurring within the epithelial perimeter of mucosal defense. Human saliva contains a number of physical, physicochemical, and chemical agents that protect oral tissues against noxious compounds. It effectively removes exogenous and endogenous microorganisms and their products into the gut and continuous presence of both nonimmune and immune factors in the mouth. Salivary mucosal pellicle forms the structural basis of the local innate immune defense mechanism of the oral mucosa.
2. Saliva proteome analysis
The salivary flow rate influences to a high degree the rate of oral and salivary clearance of bacterial substrates included in foods and snacks. Salivary IgA and lysozyme were inversely correlated with self-perceived work-related stress. As these salivary biomarkers are reflective of the mucosal immunity, results support the inverse relation between stress and mucosal immunity.There was an inverse relationship between the presence of hyaluronidase and the presence of hyaluronidase inhibitors particularly in relation to intraoral wound healing and periodontal disease. Human salivary α-amylase (HSA) is a major secretory protein component of saliva and has important biological functions, including the initial digestion of starch. The collagen-cleaving enzyme matrix metalloproteinase-8 (MMP-8) is present in saliva and acts as measurable indicator of periodontal disease.
Amylase present in human saliva was one of the first enzymes to be recognized and molecular mechanisms involved in amylolysis of starch and even of the physiological role of the salivary amylase itself. Lactoferrin in saliva represents an important defense factor against bacterial injuries including those related toStreptococcus mutans and periodontopathic bacteria through its ability to decrease bacterial growth, biofilm development, iron overload, reactive oxygen formation, and inflammatory processes. Some defense proteins, like salivary immune globulins and salivary chaperokine HSP70/HSPAs, are involved in both innate and acquired immunities. Lactoferrin is a major component of biologically important mucosal fluids and is essential for mucosal-mediated immunity
The antimicrobial in vitro effects of the salivary proteins lactoferrin and lysozyme on microorganisms is involved in the carious process, obtaining their minimum inhibitory concentration and minimum bactericidal concentration. Salivary alpha-amylase has been proposed as a sensitive noninvasive biomarker for stress-induced changes in the body that reflect the activity of the sympathetic nervous system. Salivary α-amylase levels may therefore serve as an effective indicator in the noninvasive assessment of physical stress. Lactoferrin is a multifunctional mammalian immunity protein that limits microbial growth through sequestration of nutrient iron. Lysozyme in saliva is found to have the antibacterial activity against the pathogen, and there is potential for it to serve an antimicrobial role in the specific application of medical industry.
Lactoferrin may be a useful agent to prevent irradiation effects in salivary glands. LTF is examined as a first-line mediator in immune defense and response to pathogenic and nonpathogenic injuries as well as a molecule critical for control of oxidative cell function. Salivary and pancreatic amylases hydrolyze starch and involvement of amylase in adiposity and starch metabolism. Lactoferrin is a secretory protein with various physiological functions, and oral lactoferrin may mitigate psychological stress in humans.
3. Role of lubrication
The complex mix of salivary constituents provides an effective set of systems for lubricating and protecting the soft and hard tissues. The lubricating and antimicrobial functions of saliva are maintained mainly by resting; saliva results in a flushing effect and the clearance of oral debris and noxious agents. Saliva is a complex fluid, which influences oral health through specific and nonspecific physical and chemical properties. Saliva contains numerous antimicrobial proteins that help protect the oral ecosystem from infectious agent. Proteins can move from blood circulation into salivary glands through active transportation, passive diffusion, or ultrafiltration; some of which are then released into saliva and hence can potentially serve as biomarkers for diseases. Saliva covers the oral hard and soft tissues with a conditioning film which governs the initial attachment of microorganisms, a crucial step in the setup of the oral microflora.
4. Role of digestion
A high quality of saliva is an essential factor to protect the dental elements against attrition and promote the digestion process. Saliva is the principal fluid component of the external environment of the taste receptor cells which is involved in the transport of taste substances and protection of the taste receptor. The role of human saliva and its compositional elements in relation to the GI functions of taste, mastication, bolus formation, enzymatic digestion, and swallowing. Salivary nonesterified fatty acids (NEFA) are proposed to play a role in oral health and oral fat detection, and they may hold diagnostic and prognostic potential.
Lingual lipase generates nonesterified fatty acids (NEFA) from dietary fats during oral processing by lipolysis. Linzgual lipase in rodents has strong lipolytic activity and plays a critical role in oral detection of fats. Physiological role of salivary lipolytic activity in the regulation of the basal FFA concentration could be involved in fat taste sensitivity. During chewing, saliva helps in preparing the food bolus by agglomerating the formed particles, and it initiates enzymatic food breakdown. Saliva plays a key role in the eating process and on the perception of flavor. Flavor corresponds to the combined effect of taste sensations, aromatics, and chemical feeling factors evoked by food in the oral cavity.
5. Role of diagnostic properties
Analysis of saliva may be useful for the diagnosis of hereditary disorders, autoimmune diseases, malignant and infectious diseases, and endocrine disorders, as well as in the assessment of therapeutic levels of drugs and the monitoring of illicit drug use. Fluid addition facilitated chewing of dry foods and feeding disorders caused by hyposalivation. Saliva has been demonstrated to be a promising bodily fluid for early detection of diseases, and salivary diagnostics have exhibited tremendous potential in clinical applications. Saliva has the potential to become a first-line diagnostic sample of choice owing to the advancements in detection technologies coupled with combinations of biomolecules with clinical relevance. Saliva is a useful diagnostic fluid for oral-related diseases. Monitoring salivary biomarkers for oral and systemic diseases could become an important complement to clinical examinations in epidemiological surveys.
The high rate of changes in the composition of saliva can be used for the monitoring of various biorhythms in order to study the physiological characteristics of the human body. The significant influences of the oral environment observed in this study increase the current understanding of the salivary microbiome in caries. These results will be useful for expanding research directions and for improving disease diagnosis, prognosis, and therapy.
6. Role of maintenance of health teeth
The role of saliva, the prevalence of oral dryness and the consequent importance of salivary flow as well as the relationship between xerostomia and salivary gland hypofunction amongst the causes of oral dryness. Saliva is the medium that bathes the taste receptors in the oral cavity and in which aroma and taste compounds are released when food is eaten. Moreover saliva contains enzymes and molecules that can interact with food. Saliva is an important fluid in the oral cavity as it bathes the teeth and the soft tissues. The salivary pH, buffer capacity and mineral content of calcium (Ca), phosphate (P), sodium (Na), and potassium (K) are important in the tooth de−/remineralization process and calculus formation. Significant change in the pH depends on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker. Taste perception elicited by food constituents and facilitated by sensory cells in the oral cavity is important for the survival of organisms. In addition to the five basic taste modalities, sweet, umami, bitter, sour, and salty, orosensory perception of stimuli such as fat constituents is intensely investigated.
Teeth are exposed to food, drinks, and the microbiota of the mouth and have a high resistance to localized demineralization that is unmatched by bone. The pH of saliva and plaque will result in white spot lesions on the tooth surface which are considered initialization of caries because of demineralization. Saliva is an important biological fluid that aids in mechanically removing food debris and bacteria from the oral cavity and teeth; reduced salivary flow causes ill effects to the oral tissues.
7. Antimicrobial, antiviral, and antifungal functions
A group of salivary proteins like lysozyme, lactoferrin, and lactoperoxidase working in conjunction with other components of saliva can have an immediate effect on oral bacteria, interfering with their ability to multiply or killing them directly. Lysozyme can cause lysis of bacterial cells, especially Streptococcus mutans, by interacting with anions of low charge density chaotropic ions (thiocyanate, perchlorate, iodide, bromide, nitrate, chloride, and fluoride) and with bicarbonate. It has recently been shown that another cationic peptide in saliva the histidine-rich peptide of parotid saliva has growth-inhibitory and bactericidal effects on oral bacteria. The histidine-rich peptides appear to be an effective antifungal agent as well, able to inhibit growth and kill Candida albicans at a very low concentration.
Lactoferrin, the exocrine gland equivalent of transferrin, is effective against bacteria that require iron for their metabolic processes. It can compete with the bacterial iron-chelating molecules and deprive the bacteria of this essential element. Lactoferrin is also capable of a bactericidal effect that is distinct from simple iron deprivation. Salivary peroxidase is part of an antibacterial system which involves the oxidation of salivary thiocyanate by hydrogen peroxide (generated by oral bacteria) to hypothiocyanite and hypothiocyanous acids. These products, in turn, affect bacterial metabolism (especially acid production) by oxidizing the sulfhydryl groups of the enzymes involved in glycolysis and sugar transport. The antimicrobial effect of salivary peroxidase against S. mutans is significantly enhanced by interaction with secretory IgA.
The protective potential of all the antibacterial proteins can be extended by interaction with mucin which can serve to concentrate this defense force at the interface of the mucosa and the inhospitable external environment. When teeth are present, especially if some gingivitis exists, the oral fluids will be augmented by a contribution from the gingival crevice area, the gingival crevicular fluid. This fluid can contribute to the oral defense system by providing (a) serum antibodies against oral bacteria, especially IgG antibodies, (b) phagocytic cells (PMNs), and (c) antibacterial products liberated from the phagocytic cells, e.g., lysozyme, lactoferrin, and myeloperoxidase.
The large number of antibacterial and antiviral proteins is present in human saliva. Of interest, most of these antibacterial proteins display antiviral activity, typically against specific viral pathogens. The review focuses on one protein that interacts with both bacteria and viruses, gp340, originally referred to as salivary agglutinin. In the oral cavity, soluble gp340 binds to and aggregates a variety of bacteria, and this is thought to increase bacterial clearance from the mouth. However, when bound to the tooth surface, gp340 promotes bacterial adherence. In the oral cavity, most gp340 proteins are found soluble in saliva and can function as a specific inhibitor of infectivity of HIV-1 and influenza A. In contrast, in the female reproductive track, most gp340 proteins are bound to the cell surface, where it can promote HIV-1 infection.
The saliva anti-fungal activity against Candida albicans andCryptococcus neoformans. Therefore, the importance of the search for new, broad-spectrum anti-fungals with little or no toxicity cannot be overemphasized. The following properties make histatins promising antifungal therapeutic agents: (1) they have little or no toxicity, (2) they possess high cidal activities against azole-resistant fungal species and most of the fungal species tested, and (3) their candidacidal activity is similar to that of azole-based antifungals. Current research efforts focus on the development of improved histatins with enhanced cidal activity and stability and of suitable and effective histatin delivery systems. These and other approaches may help to outpace the growing list of drug-resistant and opportunistic fungi causing life-threatening, disseminating diseases. The histatins with improved protective properties may also be used as components of artificial saliva for patients with salivary dysfunction.
Acknowledgment