A new approach to prevent radiation-induced xerostomia using intraglandular injection of mitochondria-boosting agents.

Radiotherapy in patients with head and neck cancer fairly leads to xerostomia, profoundly affecting their quality of life. With limited effective preventive and therapeutic methods, attention has turned to exploring alternatives. This article outlines how intraglandular injection of mitochondria-boosting agents can serve as a potential strategy to reduce salivary acinar damage. This method can contribute to the thoughtful development of study protocols or medications to reduce radiation-induced salivary glands damage.

Reversal of Valproate-Induced Major Salivary Gland Changes By Moringa Oleifera Extract in Rats.

This study aimed to explore the potential protective impacts of Moringa oleifera extract on major alteration in salivary glands of rats exposed to sodium valproate (VA). Groups were defined as control, control+moringa extract, sodium valproate, and sodium valproate+moringa extract. Antioxidant and oxidant status, activities of digestive and metabolic enzymes were examined. VA treatment led to various biochemical changes in the salivary glands, including decreased levels of antioxidants like glutathione, glutathione-S-transferase, and superoxide dismutase (except for sublingual superoxide dismutase). Conversely, a decrease in alpha-amylase, alkaline and acid phosphatase, lactate dehydrogenase, protease, and maltase activities were observed. The study also demonstrated that VA induces oxidative stress, increases lipid peroxidation, sialic acid, and nitric oxide levels in the salivary glands. Total oxidant capacity was raised in all glands except in the sublingual gland. The electrophoretic patterns of proteins were similar. Moringa oleifera extract exhibited protective properties, reversing these VA-induced biochemical changes due to its antioxidant and therapeutic attributes. This research suggests that moringa extract might serve as an alternative treatment approach for individuals using VA and experiencing salivary gland issues, although further research is necessary to confirm these findings in human subjects.

Transdermal pilocarpine on the skin over salivary glands to increase salivation: an in vivo study.

BACKGROUND: Hyposalivation is treated using oral cholinergic drugs; however, systemic side effects occasionally lead to discontinuation of treatment. We aimed to investigate the effects of transdermal pilocarpine on the salivary gland skin on saliva secretion and safety in rats. METHODS: Pilocarpine was administered to rats orally (0.5 mg/kg) or topically on the salivary gland skin (5 mg/body). Saliva volume, the number of sweat dots, and fecal weight were measured along with pilocarpine concentration in plasma and submandibular gland tissues. RESULTS: Saliva volume significantly increased 0.5 h after oral administration and 0.5, 3, and 12 h after topical administration. Fecal weight and sweat dots increased significantly 1 h after oral administration; however, no changes were observed after topical application. The pilocarpine concentration in the submandibular gland tissues of the topical group was higher than that in the oral group at 0.5, 3, and 12 h of administration. CONCLUSIONS: Pilocarpine application to salivary gland skin persistently increased salivary volume in rats without inducing sweating or diarrhea. Transdermal pilocarpine applied to the skin over the salivary glands may be an effective and safe treatment option for hyposalivation.

The Usefulness of Salivary Gland Organoids for Evaluation of the Potency of Botulinum Neurotoxin.

BACKGROUND AND OBJECTIVES: Botulinum neurotoxin (BoNT) is a substance used to treat chronic sialorrhea, muscle dystonia, and is used in cosmetic applications. Measuring the potency of BoNT is crucial because it acts even with a small amount. However, the current methods for measuring the potency of BoNT involve using two-dimensional neuroblastoma cell line-based methods. In this study, we aimed to develop a new method to measure the potency of BoNT using a three-dimensional organoid culture system. MATERIALS AND METHOD: We established the optimal conditions for coculturing N2a neuronal cells with murine salivary gland organoids (SGOs). After determining the appropriate chemical concentrations, we treated the SGOs cocultured with N2a cells with BoNT type A (BoNT/A). We confirmed the expression of salivary gland-related genes and proteins using real-time polymerase chain reaction (PCR) and immunofluorescence staining. RESULTS: The SGOs cocultured with N2a cells showed that the dendrites or axons of neuronal cells were in contact with the outermost layer of the SGOs. When we applied acetylcholine and neostigmine to the coculture systems, the mRNA expression of Aqp5 and Bhlha15, associated with salivary gland secretory cells, increased. However, this effect was reversed when BoNT/A was applied, as confirmed through real-time PCR. CONCLUSION: We found that the coculture system of SGOs and N2a neuronal cells can potentially serve as a potency testing platform for BoNT. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2697-2704, 2024.

CORRECTION OF PATHOLOGICAL CHANGES IN SALIVARY GLANDS OF ANIMALS WITH PACLITAXEL-INDUCED NEUROPATHY.

BACKGROUND: Paclitaxel is a highly effective chemotherapeutic agent used to treat breast, ovarian, and other cancers. At the same time, paclitaxel causes peripheral neuropathy as a side effect in 45%-70% of patients. AIM: The aim of the study was to investigate the effect of paclitaxel-induced peripheral neuropathy on the development of pathological changes in the salivary glands of animals and to explore the possibility of correction of the identified changes with vitamin B/ATP complex. MATERIALS AND METHODS: To simulate toxic neuropathy, animals were injected i/p with paclitaxel 2 mg/kg for 4 days. In order to correct the identified changes, rats were injected i/m with vitamin B/ATP complex (1 mg/ kg) for 9 days. In the homogenate of the submandibular salivary glands, α-amylase activity, total proteolytic activity, total antitryptic activity, the content of medium mass molecules, thiobarbituric acid reactive substances (TBARS), oxidatively modified proteins, and catalase activity were determined. RESULTS: A significant increase in the content of oxidatively modified proteins, medium mass molecules, and the content of TBARS and significant decrease in the activity of catalase and amylase were determined in the salivary glands of animals with toxic neuropathy compared to these parameters in intact animals. Administration of vitamin B/ATP complex for 9 days against the background of paclitaxel-induced neuropathy led to normalization of antitryptic activity and amylase activity, a significant decrease in the content of oxidatively modified proteins, medium mass molecules, and TBARS along with a significant increase in catalase activity in the salivary glands of animals compared to the untreated rats with neuropathy. CONCLUSION: Paclitaxel-induced neuropathy caused the development of pathological changes in the salivary glands of rats, which was evidenced by a carbonyl- oxidative stress and impaired protein synthetic function. The correction with vitamin B/ATP complex restored the protein-synthetic function and the proteinase-inhibitor balance, suppressed the oxidative stress and normalized free radical processes in the salivary glands of rats.

Salivary toxicity from PSMA-targeted radiopharmaceuticals: What we have learned and where we are going.

Clinical trials of prostate-specific membrane antigen (PSMA) targeted radiopharmaceuticals have shown encouraging results. Some agents, like lutetium-177 [177Lu]Lu-PSMA-617 ([177Lu]Lu-PSMA-617), are already approved for late line treatment of metastatic castration-resistant prostate cancer (mCRPC). Projections are for continued growth of this treatment modality; [177Lu]Lu-PSMA-617 is being studied both in earlier stages of disease and in combination with other anti-cancer therapies. Further, the drug development pipeline is deep with variations of PSMA-targeting radionuclides, including higher energy alpha particles conjugated to PSMA-honing vectors. It is safe to assume that an increasing number of patients will be exposed to PSMA-targeted radiopharmaceuticals during the course of their cancer treatment. In this setting, it is important to better understand and mitigate the most commonly encountered toxicities. One particularly vexing side effect is xerostomia. In this review, we discuss the scope of the problem, inventories to better characterize and monitor this troublesome side effect, and approaches to preserve salivary function and effectively palliate symptoms. This article aims to serve as a useful reference for prescribers of PSMA-targeted radiopharmaceuticals, while also commenting on areas of missing data and opportunities for future research.

Evaluation of photobiomodulation in the salivary production of patients with hyposalivation induced by antihypertensive drugs - A blind, randomized, controlled clinical trial.

BACKGROUND: Arterial hypertension is a systemic condition that affects about 35% of the world population. The drugs that are used for its control can produce hyposalivation. This work evaluated the effect of photobiomodulation on salivary flow rate, salivary pH, total protein concentration, and calcium concentration in individuals using antihypertensive medications. MATERIAL AND METHODS: 41 subjects were randomly allocated in one of two groups: control (placebo) and photobiomodulation. The subjects had their salivary glands (20 sites) irradiated with a laser emitting at 808 nm, 4J/site once a week for 4 weeks and had their salivary flow measured before and after the whole treatment. RESULTS: The intragroup analysis (before and after treatment) shows a significant difference for both non-stimulated and stimulated salivary flow in the photobiomodulation group (p = 0.0007 and p = 0.0001, respectively). Comparing the placebo with the photobiomodulation group, significant differences were found for both non-stimulated (p = 0.0441) and stimulated salivary flow (p = 0.0441) after the treatment. No significant differences were found in pH, total protein concentration, calcium concentration. CONCLUSION: Despite the usage of drugs that influence the nervous system and typically result in a reduction of saliva production, photobiomodulation demonstrated a remarkable ability to enhance saliva production by a significant 75%.

Retroductal dexamethasone administration promotes the recovery from obstructive and inflammatory salivary gland dysfunction.

Introduction: Salivary gland dysfunction, often resulting from salivary gland obstruction-induced inflammation, is a prevalent condition. Corticosteroid, known for its anti-inflammatory and immunomodulatory properties, is commonly prescribed in clinics. This study investigates the therapeutic implications and potential side effects of dexamethasone on obstructive sialadenitis recovery using duct ligation mice and salivary gland organoid models. Methods: Functional and pathological changes were assessed after administering dexamethasone to the duct following deligation 2 weeks after maintaining ligation of the mouse submandibular duct. Additionally, lipopolysaccharide- and tumor necrosis factor-induced salivary gland organoid inflammation models were established to investigate the effects and underlying mechanisms of action of dexamethasone. Results: Dexamethasone administration facilitated SG function restoration, by increasing salivary gland weight and saliva volume while reducing saliva lag time. Histological evaluation revealed, reduced acinar cell atrophy and fibrosis with dexamethasone treatment. Additionally, dexamethasone suppressed pro-inflammatory cytokines IL-1ß and TNF expression. In a model of inflammation in salivary gland organoids induced by inflammatory substances, dexamethasone restored acinar markers such as AQP5 gene expression levels, while inhibiting pro-inflammatory cytokines TNF and IL6, as well as chemokines CCL2, CXCL5, and CXCL12 induction. Macrophages cultured in inflammatory substance-treated media from salivary gland organoid cultures exhibited pro-inflammatory polarization. However, treatment with dexamethasone shifted them towards an anti-inflammatory phenotype by reducing M1 markers (Tnf, Il6, Il1b, and Cd86) and elevating M2 markers (Ym1, Il10, Cd163, and Klf4). However, high-dose or prolonged dexamethasone treatment induced acino-ductal metaplasia and had side effects in both in vivo and in vitro models. Conclusions: Our findings suggest the effectiveness of corticosteroids in treating obstructive sialadenitis-induced salivary gland dysfunction by regulating pro-inflammatory cytokines.

Types I and III parotid collagen variations and serum biochemical parameters in obese rats exposed to monosodium glutamate / Variaciones de colágeno parotídeo tipos I y III y parámetros bioquímicos séricos en ratas obesas expuestas a glutamato monosódico

SUMMARY: The objective of this study was to describe the effects of monosodium glutamate on the collagen of the parotid gland in an obesity model. 18 newborn male Sprague Dawley rats were used (first control group; second group of MSG1: 4 mg/g of monosodium glutamate weight, 5 doses, and third group of MSG2: 4 mg/g of monosodium glutamate, 5 doses, maintained for 8 and 16 weeks respectively). The content and type of collagen were analyzed, in addition to the levels of cholesterol, glucose, triglycerides and uric acid. Monosodium glutamate produced an increase in the obesity rates of the MSG2 group, in addition to an increase in blood cholesterol, glucose and uric acid levels compared to the control group. Type III collagen in the MSG2 group showed a statistically significant increase. Monosodium glutamate induced obesity, in addition to an increase in type III collagen fibers.

RESUMEN: El objetivo de este estudio fue describir los efectos del glutamato monosódico sobre el colágeno de la glándula parótida en un modelo de obesidad. Se utilizaron 18 ratas Sprague Dawley machos recién nacidas (primer grupo control; segundo grupo MSG1: 4 mg/g de peso de glutamato monosódico, 5 dosis, y tercer grupo MSG2: 4 mg/g de glutamato monosódico, 5 dosis, mantenidas durante 8 y 16 semanas respectivamente). Se analizó el contenido y el tipo de colágeno, además de los niveles de colesterol, glucosa, triglicéridos y ácido úrico. El glutamato monosódico produjo un aumento en las tasas de obesidad del grupo MSG2, además de un aumento en los niveles de colesterol en sangre, glucosa y ácido úrico en comparación con el grupo control. El colágeno tipo III en el grupo MSG2 mostró un aumento estadísticamente significativo. La obesidad inducida por glutamato monosódico, además de un aumento en las fibras de colágeno tipo III.

Investigation of the effect of GnRH (deslorelin) on the histochemical structure of salivary glands in rats / Investigación del efecto de la GnRH (deslorelina) sobre la estructura histoquímica de las glándulas salivales en ratas

This study was planned to determine the histochemical alterations of the submandibular gland by implantation of long-term GnRH (deslorelin 4.7 mg). Eighteen Wistar albino rats were used in the study. Alcian blue (AB; pH: 2.5), periodic acid-Schiff (PAS) staining was performed to determine the microscopic structure and histochemical structure of the GI submandibular gland. The Avidin-Biotin Complex (ABC) method was used to determine the immunohistochemical reactivity of lectin. After GnRH implantation, the organs were examined and atrophies were observed in organs. In the group in which the implants were removed, it was determined that there was no atrophy; organ structures and microscopic examination were similar to the control group. At the end of the study, submandibular gland was fixed in 10 % buffered formaldehyde. In three groups, PAS and AB histochemical staining revealed similar reactions. Immunohistochemically, lectin activity was found to react positively.

Este estudio se planificó para determinar las alteraciones histoquímicas de la glándula submandibular mediante la implantación de GnRH a largo plazo (deslorelina 4,7 mg). Dieciocho ratas Wistar albinas se utilizaron en el estudio. Para determinar la estructura microscópica e histoquímica de la glándula submandibular, se realizó una tinción con azul alcián (AA; pH: 2.5) y ácido peryódico de Schiff (PAS). El método Avidin-Biotin Complex (ABC) se utilizó para determinar la reactividad inmunohistoquímica de la lectina. Después de la implantación de GnRH, se examinaron los órganos y se observó atrofia en ellos. En el grupo en el que se retiraron los implantes, no se observó atrofia. Las estructuras orgánicas y el examen microscópico fueron similares al grupo control. Al final del estudio, la glándula submandibular se fijó en formaldehído tamponado al 10 %. En tres grupos, la tinción histoquímica de PAS y AA reveló reacciones simila4res. Inmunohisto-químicamente, se encontró que la actividad de la lectina reaccionó positivamente.

Xerostomia em pacientes com HIV/ Aids: revisão sistemática de literatura

Introdução: a transmissão do vírus da imunodeficiênciahumana (HIV) leva à redução da resposta imunológicado indivíduo, podendo ocorrer alterações na cavidadebucal, entre elas, a xerostomia. Objetivo: por meio deuma revisão sistemática, este trabalho objetiva analisara presença e as correlações da presença de xerostomiaem pacientes HIV positivos ou com Aids. Métodos: foifeita busca nas bases de dados PubMed, SciELO e Lilacsutilizando os descritores "oral manifestations", "HIV","Aids" e "xerostomia", sendo os critérios de inclusãotrabalhos epidemiológicos descritivos e observacionaiscom no máximo 10 anos de publicação e em línguainglesa, portuguesa ou espanhola. Resultados: foramencontrados 162 artigos que, após critérios exclusivos,foram reduzidos a 15 trabalhos desenvolvidos em setepaíses, nos quais se encontraram valores variando entre2% e 76,2% na presença de xerostomia em pacientescom HIV/Aids, a maioria homens entre a terceira e aquarta década de vida. Conclusão: a xerostomia em pacientescom HIV/Aids necessita de diversas pesquisasclínicas, devido aos inúmeros fatores que podem ocasionara etiologia, além da grande divergência de resultadosencontrados. Estudos afirmam que patologias queacometem as glândulas salivares podem levar à sensaçãode boca seca nesses indivíduos e são decorrentesda utilização prolongada da terapia antirretroviral altamenteativa (Haart). (AU)

Introduction: the human immunodeficiency virus transmission reduces the immune response of individuals and may cause changes in the oral cavity, such as xerostomia. Objective: by means of a systematic review, the present study aims to analyze the presence and correlations of the presence of xerostomia in HIV+ patients or those living with AIDS. Methods: the databases PubMed, SciELO, and Lilacs were searched using the descriptors "oral manifestations", "HIV", "AIDS", and "xerostomia". Inclusion criteria consisted of observational descriptive epidemiological studies with up to 10 years of publication, in English, Portuguese, or Spanish. Results: a total of 162 articles were found, which after exclusive criteria were reduced to the quantity of 15 studies from seven countries. These studies found varying values in the presence of xerostomia in HIV/ AIDS patients, ranging from 2% to 76.2%, most of them in men between the third and fourth decades of life. Conclusion: xerostomia in HIV/AIDS patients requires several clinical studies due to the numerous factors that may cause the etiology, besides the great divergence of results found. Studies indicate that pathologies affecting the salivary glands may cause dry mouth sensation in these patients, which derives from the prolonged use of Highly Active Antiretroviral Therapy (HAART). (AU)

Drugs or disease: evaluating salivary function in RA patients

Abstract Oral complications of RA may include temporomandibular joint disorders, mucosa alterations and symptoms of dry mouth. The aim of this study was to evaluate the salivary gland function of subjects with rheumatoid arthritis (RA) comparing it to healthy controls. Subjects with other systemic conditions known to affect salivary functions were excluded. A questionnaire was applied for the evaluation of xerostomia. Resting and chewing-stimulated salivary flow rates (SFR) were obtained under standard conditions. There were 145 subjects included of the study (104 RA and 38 controls). About 66.7% of the RA subjects and 2.4% in control group presented xerostomia. The median resting SFR were 0.24 ml/min for RA subjects and 0.40 mL/min for controls (p = 0.04). The median stimulated SFR were 1.31 mL/min for RA subjects and 1.52 ml/min for controls (p = 0.33). No significant differences were found between resting and stimulated SFR of RA subjects not using xerogenic medications and controls. There was significantly higher number of subjects presenting hyposalivation in the RA group than among controls, even when subjects using xerogenic medications were eliminated from the analysis. In conclusion, hyposalivation and xerostomia were more frequent among RA subjects not using xerogenic medication than among controls, although there were no significant differences in the median SFR between groups.

5-Bromo-2’-deoxyuridine induces visible morphological alteration in the DNA puffs of the anterior salivary gland region of Bradysia hygida (Diptera, Sciaridae)

5-Bromo-2’-deoxyuridine (BrdUrd) has long been known to interfere with cell differentiation. We found that treatment ofBradysia hygida larvae with BrdUrd during DNA puff anlage formation in the polytene chromosomes of the salivary gland S1 region noticeably affects anlage morphology. However, it does not affect subsequent metamorphosis to the adult stage. The chromatin of the chromosomal sites that would normally form DNA puffs remains very compact and DNA puff expansion does not occur with administration of 4 to 8 mM BrdUrd. Injection of BrdUrd at different ages provoked a gradient of compaction of the DNA puff chromatin, leading to the formation of very small to almost normal puffs. By immunodetection, we show that the analogue is preferentially incorporated into the DNA puff anlages. When BrdUrd is injected in a mixture with thymidine, it is not incorporated into the DNA, and normal DNA puffs form. Therefore, incorporation of this analogue into the amplified DNA seems to be the cause of this extreme compaction. Autoradiographic experiments and silver grains counting showed that this treatment decreases the efficiency of RNA synthesis at DNA puff anlages.

Dissociation between vasodilation and Leishmania infection-enhancing effects of sand fly saliva and maxadilan

In this study, the ability of maxadilan and Lutzomyia longipalpis salivary gland lysate to enhance the infection of CBA mice by Leishmania major and of BALB/c mice by L. braziliensis was tested. No difference was observed between sizes of lesion in CBA mice infected with L. major and treated or not with salivary gland lysate or maxadilan, although they were injected in concentrations that induced cutaneous vasodilation. Although parasites were more frequently observed in foot pads and spleens of animals treated with maxadilan than in the animals treated with salivary gland lysate or saline, the differences were small and not statistically significant. The lesions in BALB/c mice infected with L. braziliensis and treated with maxadilan were slightly larger than in animals that received Leishmania alone. Such differences disappeared 14 weeks after infection, and were statistically significant only in one of two experiments

Influência do oleato de sódio ministrado por intubagem gástrica na incidência de cárie em ratos intactos e com os ductos das glândulas salivares atados / The influence of sodium oleate administrated by gastric intubation on the incidence of dental caries in rats with intact and ligated salivary gland ducts

O efeito do oleato de sódio ministrado por intubagem gástrica sobre a incidência de cárie em ratos intactos e com seus ductos das glândulas salivares atados foi estudado. Ratos intactos que receberam o oleato de sódio apresentaram um aumento na incidência de cárie comparado aos controles que receberam soluçäo fisiológica de cloreto de sódio. Por outro lado, ratos que tiveram seus ductos glandulares atados e que receberam oleato de sódio, apresentaram uma diminuiçäo na incidência de cárie. O atamento dos ductos das glândulas salivares aumentou a incidência de cárie, independentemente da ministraçäo gástrica de oleato de sódio. Conclue-se que a açäo anticariogênica descrita anteriormente para o oleato de sódio quando ministrado na dieta cariogênica de rato seja devido à inibiçäo da fermentaçäo bacteriana da placa dentária. A razäo pela qual o oleato de sódio diminuiu a incidência de cárie em ratos com os ductos glandulares atados ainda näo é conhecida