Structural and functional injury in minipig salivary glands following fractionated exposure to 70 Gy of ionizing radiation: an animal model for human radiation-induced salivary gland injury

2003 ◽  
Vol 96 (3) ◽  
pp. 267-274 ◽  
Author(s):  
Lida Radfar ◽  
David A Sirois
Keyword(s):  
Animal Model ◽  
Salivary Gland ◽  
Ionizing Radiation ◽  
Salivary Glands ◽  
Radiation Induced

Bone Marrow-Derived Stem Cells Reduce Radiation-Induced Damage to Salivary Glands.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1194-1194
Author(s):  
Pieter K. Wierenga ◽  
Isabelle Lombaert ◽  
Willy Visser ◽  
Harm H. Kampinga ◽  
Gerald de Haan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Salivary Gland ◽  
Salivary Glands ◽  
Laser Fluorescence ◽  
Egfp Expression ◽  
Confocal Laser ◽  
Optimal Time ◽  
Similar Amount ◽  
Radiation Induced

Abstract The salivary glands are often included in the field of irradiation during radiotherapy of head and neck cancer. This can result in severe side-effects that reduces the quality of life of the patient and may even limit the treatment dose. Late damage to the salivary glands is mainly caused by exhaustion of the tissue specific stem cells. Post-irradiation replacement of salivary gland stem cells with donor stem cells may ameliorate radiation-induced complications. Bone marrow-derived stem cells (BMSC) have been shown to be multipotent and thereby able to engraft in many tissues after injury. In this study, we assessed the potential of BMSC to reduce irradiation-induced salivary gland damage. C57BL/6 mice were transplanted with bone marrow from eGFP transgenic animals. After two months the salivary glands of these chimeric mice were locally irradiated with 15 Gy. BMSC were mobilized 10, 30 and/or 60 days after irradiation by s.c. injection of rHu-PEG-G-CSF. Saliva secretion (μl/15 minutes) was measured up to 90 days after irradiation by pilocarpine induction. Hereafter, the glands were extirpated and examined for eGFP-expression. From every individual animal one parotid and one submandibular gland was used to prepare single cell suspensions in order to detect eGFP-positve cells by flow cytometry. The other parotid and submandibular glands were analyzed using confocal laser fluorescence scanning microscopy and light microscopy. G-CSF treatment yielded in an increase of saliva flow for all time points. The optimal time-point for mobilization, however, was 30 days after irradiation as is demonstrated by an improvement of salivary flow from 5 to 30% when compared to radiation alone. FACS analysis showed that up to 10% of the isolated cells were eGFP-positive. Microscopic analysis revealed a similar amount of positive cells and an improved morphology. Immuno-histochemistry using anti-SM-actin antibodies showed the close vicinity of actin and eGFP within the cells, demonstrating the occurence of BMSC derived myoepithelial cells in irradiated salivary glands. Furthermore, using cell-type specific antibodies, the meyoepethilial nature of the eGFP positive was revealed. In conclusion, the results show that BMSC home to severely damaged salivary glands after mobilization. Hence, BMSC mobilization could become a promising modality to ameliorate radiation-induced complications in salivary glands after radiotherapy.

scholarly journals Integration of metabolomics and transcriptomics reveals convergent pathways driving radiation-induced salivary gland dysfunction

2021 ◽  
Author(s):  
Lauren Gayle Meeks ◽  
Diogo De Oliveira Pessoa ◽  
Jessica Anne Martinez ◽  
Kirsten H. Limesand ◽  
Megha Padi
Keyword(s):  
Salivary Gland ◽  
Energy Metabolism ◽  
Head And Neck ◽  
Salivary Glands ◽  
Metabolic Phenotype ◽  
Glutathione Metabolism ◽  
Metabolic Reaction ◽  
Salivary Gland Dysfunction ◽  
Damage Response ◽  
Radiation Induced

Radiation therapy for head and neck cancer causes damage to the surrounding salivary glands, resulting in salivary gland hypofunction and xerostomia. Current treatments do not provide lasting restoration of salivary gland function following radiation; therefore, a new mechanistic understanding of the radiation-induced damage response is necessary for identifying therapeutic targets. The purpose of the present study was to investigate the metabolic phenotype of radiation-induced damage in parotid salivary glands by integrating transcriptomic and metabolomic data. Integrated data were then analyzed to identify significant gene-metabolite interactions. Mice received a single 5 Gy dose of targeted head and neck radiation. Parotid tissue samples were collected 5 days following treatment for RNA sequencing and metabolomics analysis. Altered metabolites and transcripts significantly converged on a specific region in the metabolic reaction network. Both integrative pathway enrichment using rank-based statistics and network analysis highlighted significantly coordinated changes in glutathione metabolism, energy metabolism (TCA cycle and thermogenesis), peroxisomal lipid metabolism, and bile acid production with radiation. Integrated changes observed in energy metabolism suggest that radiation induces a mitochondrial dysfunction phenotype. These findings validated previous pathways involved in the radiation-damage response, such as altered energy metabolism, and identified robust signatures in salivary glands, such as reduced glutathione metabolism, that may be driving salivary gland dysfunction.

scholarly journals Sensitivity of Salivary Glands to Radiation: from Animal Models to Therapies

2009 ◽  
Vol 88 (10) ◽  
pp. 894-903 ◽  
Author(s):  
O. Grundmann ◽  
G.C. Mitchell ◽  
K.H. Limesand
Keyword(s):  
Quality Of Life ◽  
Head And Neck Cancer ◽  
Salivary Gland ◽  
Animal Models ◽  
Salivary Glands ◽  
Clinical Implications ◽  
Future Directions ◽  
Radiation Induced ◽  
Secondary Side

Radiation therapy for head and neck cancer causes significant secondary side-effects in normal salivary glands, resulting in diminished quality of life for these individuals. Salivary glands are exquisitely sensitive to radiation and display acute and chronic responses to radiotherapy. This review will discuss clinical implications of radiosensitivity in normal salivary glands, compare animal models used to investigate radiation-induced salivary gland damage, address therapeutic advances, and project future directions in the field.

scholarly journals Sox9+ Cell is Required for Salivary Gland Regeneration after Radiation Damage via Wnt/β-Catenin Pathway

2021 ◽  
Author(s):  
Xiuyun Xu ◽  
Xiong Gan ◽  
Ming Zhang ◽  
Jiaxiang Xie ◽  
Shuang Chen ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Cell Lineage ◽  
Term Treatment ◽  
Sequencing Data ◽  
Long Term Treatment ◽  
Radiation Induced ◽  
Gland Function ◽  
Salivary Gland Regeneration

Abstract Background: Radiotherapy for head and neck cancer can cause serious side effects, including severe damage to the salivary glands, resulting in symptoms such as xerostomia, dental caries, oral infectious and so on. Due to lack of long-term treatment for the symptoms of saliva barren, current research has focused on finding endogenous stem cells that can differentiate into various cell lineage to replace lost tissue and restore function. Results: In our study, we identified Sox9+ cells can differentiate into various salivary epithelial cell lineages under homeostatic conditions. After ablating Sox9+ cells, the salivary glands of irradiated mice showed more severe phenotypes and reduced proliferative capacity. Analysis of online single cell RNA-sequencing data revealed enrichment of the Wnt/β-catenin pathway in Sox9+ cell population. Furthermore, treatment of Wnt/β-catenin inhibitor to irradiated mice inhibited the regenerative capability of Sox9+ cells. Finally, we showed that Sox9+ cells were able to form organoids in vitro and transplanting these organoids into salivary glands after radiation restored part of salivary gland function. Conclusions: In short, our research indicated that regenerative therapy targeting Sox9+ cells is a promising method to solve the radiation induced salivary gland injury.

Radiation-induced surface decomposition

1983 ◽  
Vol 41 ◽  
pp. 368-369
Author(s):  
M. L. Knotek
Keyword(s):  
Ionizing Radiation ◽  
Atomic Structure ◽  
Chemical Bonding ◽  
Neutral Species ◽  
Radiation Induced ◽  
Physical And Chemical ◽  
Surface Decomposition ◽  
The Relationship ◽  
Electron And Photon ◽  
Surface Bond

Modern surface analysis is based largely upon the use of ionizing radiation to probe the electronic and atomic structure of the surfaces physical and chemical makeup. In many of these studies the ionizing radiation used as the primary probe is found to induce changes in the structure and makeup of the surface, especially when electrons are employed. A number of techniques employ the phenomenon of radiation induced desorption as a means of probing the nature of the surface bond. These include Electron- and Photon-Stimulated Desorption (ESD and PSD) which measure desorbed ionic and neutral species as they leave the surface after the surface has been excited by some incident ionizing particle. There has recently been a great deal of activity in determining the relationship between the nature of chemical bonding and its susceptibility to radiation damage.

Amifostine-Loaded Dissolving Armored Microneedles for Long-Term Prevention of Ionizing Radiation-Induced Injury

2020 ◽  
Author(s):  
Xiang Yu ◽  
Minshu Li ◽  
Lin Zhu ◽  
Jingfei li ◽  
Guoli Zhang ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Radiation Induced

Evaluation of the Radioprotective Effects of Melatonin Against Ionizing Radiation-Induced Muscle Tissue Injury

2019 ◽  
Vol 12 (3) ◽  
pp. 247-255 ◽  
Author(s):  
Dheyauldeen Shabeeb ◽  
Mansoor Keshavarz ◽  
Alireza Shirazi ◽  
Gholamreza Hassanzadeh ◽  
Mohammed Reza Hadian ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Gastrocnemius Muscle ◽  
Tissue Injury ◽  
Histopathological Examination ◽  
Compound Action Potential ◽  
Optimal Dose ◽  
Treatment Method ◽  
Major Product ◽  
Muscle Tissues ◽  
Radiation Induced

Background: Radiotherapy (RT) is a treatment method for cancer using ionizing radiation (IR). The interaction between IR with tissues produces free radicals that cause biological damages.As the largest organ in the human body, the skeletal muscles may be affected by detrimental effects of ionizing radiation. To eliminate these side effects, we used melatonin, a major product secreted by the pineal gland in mammals, as a radioprotective agent. Materials and Methods: For this study, a total of sixty male Wistar rats were used. They were allotted to 4 groups: control (C), melatonin (M), radiation (R) and melatonin + radiation (MR). Rats’ right hind legs were irradiated with 30 Gy single dose of gamma radiation, while 100 mg/kg of melatonin was given to them 30 minutes before irradiation and 5 mg/ kg once daily afternoon for 30 days. Five rats in each group were sacrificed 4, 12 and 20 weeks after irradiation for histological and biochemical examinations. Results: Our results showed radiation-induced biochemical, histological and electrophysiological changes in normal rats’ gastrocnemius muscle tissues. Biochemical analysis showed that malondialdehyde (MDA) levels significantly elevated in R group (P<0.001) and reduced significantly in M and MR groups after 4, 12, and 20 weeks (P<0.001), However, the activity of catalase (CAT) and superoxide dismutase(SOD)decreased in the R group and increased in M and MR groups for the same periods of time compared with the C group (P<0.001), while melatonin administration inverted these effects( P<0.001).Histopathological examination showed significant differences between R group for different parameters compared with other groups (P<0.001). However, the administration of melatonin prevented these effects(P<0.001). Electromyography (EMG) examination showed that the compound action potential (CMAP) value in the R group was significantly reduced compared to the effects in the C and M groups after 12 and 20 weeks (P<0.001). The administration of melatonin also reversed these effects (P<0.001). Conclusion: Melatonin can improve biochemical, electrophysiological and morphological features of irradiated gastrocnemius muscle tissues.Our recommendation is that melatonin should be administered in optimal dose. For effective protection of muscle tissues, and increased therapeutic ratio of radiation therapy, this should be done within a long period of time.

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