Wetting the whistle: neurotropic factor improves salivary function

Swick, Adam D.; Kimple, Randall J.

doi:10.1172/jci77194

Cited by 5 publications

(6 citation statements)

References 18 publications

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“…Xerostomia is a common side effect of numerous medications and other therapies, especially found in patients that have received radiotherapy for the treatment of head and neck cancer and in elderly individuals [21,22]. Current treatments for xerostomia include salivary substitutes, hyperbaric oxygen and gene therapy as well as salivary stimulants such as pilocarpine (a non-selective muscarinic receptor agonist) [23][24][25]. However, these treatments still have the potential risk for undesirable adverse effects [26].…”

Section: Discussionmentioning

confidence: 99%

“…These suggests that cordycepin especially at low concentrations did not display a toxic effect to the HSG. In addition, the cell viability at different time points (24,48, and 72 h) showed that % cell viability of HSG remains unchanged at various time points, indicating that cordycepin had no proliferative effects on HSG cells (Figure 1B). The percentage of viable HSG cells was considerably decreased upon exposure to H2O2 (Figure 1C), indicating cytotoxicity.…”

Section: Cordycepin Prevents Against H 2 O 2 -Induced Toxicity In Hsg Cellsmentioning

confidence: 97%

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Cordycepin attenuates Salivary Hypofunction through the Prevention of Oxidative Stress in Human Submandibular Gland Cells

et al. 2020

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Xerostomia (dry mouth) is a significant age-related condition. Meanwhile, cordycepin, the natural therapeutic agent, has demonstrated an anti-aging effect. Therefore, the present study aimed to investigate the preventive effects of cordycepin on secretory function in an in vitro model of hydrogen peroxide (H 2 O 2 )-induced salivary hypofunction. After being exposed to H 2 O 2 , human submandibular gland (HSG) cells were treated with various concentrations of cordycepin (6.25-50 µM) for 24, 48, and 72h. To evaluate cell proliferation and reactive oxygen species (ROS) generation, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and 2, 7'-dichlorodihydrofluorescein diacetate assays were performed. The amylase activity was kinetically measured by 2-chloro- p -nitrophenol linked with maltotrioside. The expression of salivary, antioxidant and apoptotic markers at mRNA and protein levels were performed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence analysis, respectively. We demonstrated that cordycepin (6.25-25 µM) contributed to significant increases in expression of the salivary marker genes, alpha-amylase 1 (AMY1A) and aquaporin-5 (AQP5), and in amylase secretion without changes in cell viability. Under oxidative stress, HSG cells showed remarkable dysfunction. Cordycepin rescued the protective effects partially by decreasing ROS generation and restoring the expression of the salivary proteins, AMY and AQP5 via anti-oxidant and anti-apoptotic activity. In addition, the amount of amylase that was secreted from HSG cells cultured in cordycepin was increased. In conclusion, cordycepin demonstrated a protective effect on H 2 O 2 - induced HSG cells by decreasing ROS generation and upregulating the salivary function markers, AMY1A and AQP5 , at both the transcriptional and translational levels.

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Section: Discussionmentioning

confidence: 99%

Section: Cordycepin Prevents Against H 2 O 2 -Induced Toxicity In Hsg Cellsmentioning

confidence: 97%

Cordycepin attenuates Salivary Hypofunction through the Prevention of Oxidative Stress in Human Submandibular Gland Cells

et al. 2020

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“…Hence, despite the understandablyalarming, at first and for some, suggestion to exogenously administer/supply cytokines and growth factors to sites of cancer, the recent years have indeed witnessed a noteworthy increase in the study of growth factors as cytoprotectants including their use as radioprotectors for salivary glands, and to reduce RT-induced symptoms, such as oral mucositis. To date, various growth factors have emerged as potential radioprotectors, including neurotrophic factors [108,109], epidermal growth factor (EGF), fibroblast growth factor (FGF) [51,110], keratinocyte growth factor (KGF) [111,112] and the afore-mentioned insulin-like growth factor-1 or IGF-1 [55,113,114]. Meyer et al, [113], for example, investigated and determined the radioprotectant and therapeutic effect of IGF-1, in a murine model.…”

Section: Surgical Intervention Alternative-to Prevent Rt-induced Hyposalivationmentioning

confidence: 99%

Salivary Gland Radio-Protection, Regeneration and Repair: Innovative Strategies

Haidar¹

2021

Biomechanics and Functional Tissue Engineering

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Saliva has a critical role in the maintenance of oral, dental and general health and well-being. Alteration(s) in the amount/quantity and/or quality of secreted saliva may induce the development of several oro-dental variations, thereby negatively-impacting overall quality of life. Diverse factors may affect the process of saliva production and quantity/quality of secretion, including medications, systemic or local pathologies and/or reversible/irreversible damage. Indeed, chemo- and/or radio-therapy, particularly, in cases of head and neck cancer, for example, are well-documented to induce serious damage and dysfunction to the radio-sensitive salivary gland tissue, resulting in hypo-salivation, xerostomia (dry mouth) as well as numerous other adverse intra−/extra-oral, medical and quality-of-life issues. Although a single governing mechanism of radiation-induced salivary gland tissue damage and dysfunction has not been yet elucidated, the potential for a synergy in radio-protection (mainly, and possible -reparation) via a combinatorial approach of mechanistically distinct strategies, has been suggested and explored over the years. This is, undoubtfully, in parallel to the ongoing efforts in improving the precision, safety and efficacy of radiotherapy protocols/outcomes, as well as in developing new technological and pharmaceutical alternatives, topics covered in this chapter.

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“…Dry mouth syndrome or xerostomia is a common radiationinduced side effect resulting from damage to salivary glands (SGs) which severely affects cancer patients' quality of life [1][2][3] Xerostomia is a multi-faceted syndrome which manifests in oral dryness and infections, dental caries, and difficulties with food mastication [1]. Currently, no cure is available therefore the main focus is optimizing regenerative potential of the gland postirradiation.…”

mentioning

confidence: 99%

“…However, knowledge on the molecular cues underlying the maintenance of mSGSCs after therapeutic irradiation is scarce. Recently, it was suggested that GDNF may play an important role in survival of mSGSCs and therefore could be used as a tool for SG function restoration after irradiation-induced damage [2,12]. GDNF is a member of GDNF family ligands, which belongs to the transforming growth factorb (TGF-b) superfamily [20].…”

mentioning

confidence: 99%