Long-term Pilocarpine Treatment Improves Salivary Flow in Irradiated Mice

Taniguchi, Akie; Susa, Taketo; Kogo, Hiroshi; Iizuka-Kogo, Akiko; Yokoo, Satoshi; Matsuzaki, Toshiyuki

doi:10.1267/ahc.19006

Cited by 14 publications

(14 citation statements)

References 41 publications

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“…Decrease in AQP1 expression within the endothelium as well as AQP5 in acinar and ductal cells has been observed along with decreased saliva secretion [ 29 , 98 , 101 ]. Long-term administration of pilocarpine to irradiated mice has a beneficial effect in terms of saliva secretion [ 102 ]. Alpha-lipoic acid also rescued radiation-induced SG hypofunction in rats [ 97 ].…”

Section: Involvement Of Aqps In Sg Pathologiesmentioning

confidence: 99%

Insight into Salivary Gland Aquaporins

D’Agostino

Elkashty

Chivasso

et al. 2020

Cells

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The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.

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Section: Involvement Of Aqps In Sg Pathologiesmentioning

confidence: 99%

Insight into Salivary Gland Aquaporins

D’Agostino

Elkashty

Chivasso

et al. 2020

Cells

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“…Activation of the muscarinic acetylcholine M3 receptor can induce aquaporin-5 transport through the transcellular pathway in parotid acinar cells and increase intracellular calcium levels and water secretion through aquaporin-5 [41]. The aquaporin-5 water channel plays a critical role in saliva secretion, as it is expressed in the apical membrane and partially in the basolateral membrane of acinar epithelial cells in the parotid and submandibular glands [42,43]. Radiation was shown to significantly decrease aquaporin-5 fluorescence intensity at the apical membrane of the submandibular acinar cells from 1 to 28 days post-irradiation [44].…”

Section: Discussionmentioning

confidence: 99%

“…As M3 receptor agonists, carbachol and pilocarpine can increase paracellular transport and cause morphological changes in the structure of the tight junctions in the rat submandibular epithelium [48,49]. Daily treatment with pilocarpine from 5 days before to 63 days after irradiation can also inhibit hyposecretion in irradiated mice | 11 of 13 IPC AND RADIATION DAMAGE TO RAT SMGS and improve secretory function [43]. This suggests that the change or disturbance in salivary tight junctions may influence both the permeability of the paracellular pathway and the production of saliva.…”

Section: Discussionmentioning

confidence: 99%

Effect of ischemic preconditioning on radiation damage to the submandibular gland in rats

Yao

Liu

Song

et al. 2021

European J Oral Sciences

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To investigate the effects of radiation on rat submandibular glands and the possible protective effects of ischemic preconditioning, the submandibular glands of Wistar rats were subjected to in situ radiation after ischemic preconditioning. The glands were exposed to X-radiation at a single dose of 20 Gy. Ischemic preconditioning was achieved by three min of ischemia and three min of reperfusion, repeated three times before irradiation. Salivary secretion, histological changes, alterations in tight junctions, and the levels of oxidative stress, pro-inflammatory cytokines, and water secretion proteins mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 weeks post-irradiation. In glands subjected to irradiation only, the secretion, superoxide dismutase activity, tight junction width, acinar cell number, and M3 receptor and aquaporin-5 levels were lower at 1 and 12 weeks than seen in the ischemically preconditioned irradiated glands. In contrast, tumor necrosis factor-α, malondialdehyde, myeloperoxidase activity, and the expression of the tight junction protein claudin-4 were significantly higher in the irradiated only glands. Our study revealed that radiation caused a series of injury-stress responses, especially damage to the water secretion pathway mediated by the M3 receptor that ultimately led to hyposecretion, which might play an important role in the dysfunction of the irradiated only glands. Ischemic preconditioning reduced the radiation-induced injury to submandibular glands and ameliorated salivary hyposecretion.

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“…The sections were deparaffinized and used for staining with hematoxylin-eosin (H&E) or immunohistochemistry. IHC was performed as described previously [27] with some modifications. The primary antibodies used in immunohistochemistry are shown in Table 1.…”

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

Differential Localization and Invasion of Tumor Cells in Mouse Models of Human and Murine Leukemias

Mashima

Azuma

Fujiwara

et al. 2020

Acta Histochem. Cytochem

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Leukemias are refractory hematopoietic malignancies, for which the development of new therapeutic agents requires in vivo studies using tumor-bearing mouse models. Although several organs are commonly examined in such studies to evaluate the disease course, the effectiveness of interventions and the localization of tumor cells in the affected organs are still unclear. In this study, we histologically examined the distribution of leukemia cells in several organs using two leukemic mouse models produced by the administration of two cell lines (THP-1, a human myelomonocytic leukemia, and A20, a mouse B cell leukemia/ lymphoma) to severe immunodeficient mice. Survival of the mice depended on the tumor burden. Although A20 and THP-1 tumor cells massively infiltrated the parenchyma of the liver and spleen at 21 days after transplantation, A20 cells were hardly found in connective tissues in Glisson's capsule in the liver as compared with THP-1 cells. In the bone marrow, there was more severe infiltration of A20 cells than THP-1 cells. THP-1 and A20 cells were widely spread in the lungs, but were rarely observed in the small intestine. These findings suggest that each leukemia model has a unique localization of tumor cells in several affected organs, which could critically affect the disease course and the efficacy of therapeutic agents, including cellular immunotherapies.

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Long-term Pilocarpine Treatment Improves Salivary Flow in Irradiated Mice

Cited by 14 publications

References 41 publications

Insight into Salivary Gland Aquaporins

Insight into Salivary Gland Aquaporins

Effect of ischemic preconditioning on radiation damage to the submandibular gland in rats

Differential Localization and Invasion of Tumor Cells in Mouse Models of Human and Murine Leukemias

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