Rat Salivary Gland Function after Fractionated Irradiation

Funegård, Ulrika; Johansson, Ingegerd; Franzén, Lars; Ericson, Thomas; Nyström, Håkan; Henriksson, Roger

doi:10.3109/02841869709109229

Cited by 10 publications

(7 citation statements)

References 31 publications

(12 reference statements)

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“…Part of the increase may be explained by normal growth (see control, Figure 6) the other part may be considered as a response to radiation and the result of tissue replenishment via dividing acinar cells and cells of the intercalated duct. Despite the increase in cell number, the function of the gland deteriorates during this period to about 30% of the nonirradiated situation, which is consistent with previous observations by others (Funegard et al, 1997;Nagler et al, 1998). This probably relates to the abnormal morphology of the (large) acini observed at this time point ( Figure 2D).…”

Section: Late Damage (120-240 Days)supporting

confidence: 91%

Early to late sparing of radiation damage to the parotid gland by adrenergic and muscarinic receptor agonists

et al. 2001

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Summary Damage to salivary glands after radiotherapeutic treatment of head and neck tumours can severely impair the quality of life of the patients. In the current study we have investigated the early-to-late pathogenesis of the parotid gland after radiation. Also the ability to ameliorate the damage using pretreatment with adrenergic or muscarinic receptor agonists is studied. Rats were locally irradiated with or without i.p. pretreatment with phenylephrine (α-adrenoceptor agonist, 5 mg kg ) (muscarinic receptor agonists) or methacholine plus phenylephrine. Parotid salivary flow rate, amylase secretion, the number of cells and gland histology were monitored sequentially up to 240 days postirradiation. The effects were described in 4 distinct phases. The first phase (0-10 days) was characterised by a rapid decline in flow rate without changes in amylase secretion or acinar cell number. The second phase (10-60 days) consists of a decrease in amylase secretion and is paralleled by acinar cell loss. Flow rate, amylase secretion and acinar cell numbers do not change in the third phase (60-120 days). The fourth phase (120-240 days) is determined by a further deterioration of gland function but an increase in acinar cell number, albeit with poor tissue morphology. All drug pretreatments used could reduce radiation effects in phase I and II. The protective effects were lost during phase IV, with the exception of methacholine plus phenylephrine pretreatment. The latter combination of drugs ameliorated radiation-damage throughout the entire follow-up time. The data show that combined pre-irradiation stimulation of muscarinic acetylcholine receptors with methacholine plus α-adrenoceptors with phenylephrine can reduce both early and late damage, possibly involving the PLC/PIP2 second messenger pathways. This opens perspectives for the development of clinical applicable methods for long-term sparing of parotid glands subjected to radiotherapy of head and neck cancer patients.

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Section: Late Damage (120-240 Days)supporting

confidence: 91%

Early to late sparing of radiation damage to the parotid gland by adrenergic and muscarinic receptor agonists

et al. 2001

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“…Various studies have revealed an over 50% reduction in parotid gland function within a few days following low irradiation doses of 2.5–10 Gy to the head and neck region. Eventually, the hypofunction exceeds 90% and the residual secreted whole‐saliva obtains mucous‐like properties (Funegard et al , 1994; Cooper et al , 1995; Liem et al , 1996; Funegard et al , 1997; Guchelaar, Vermes and Meerwaldt, 1997; Fox, 1998; Rode et al , 1999; Roesink et al , 1999; Taylor and Miller, 1999). Numerous morphological studies have demonstrated the destruction of serous cells with sparing of mucous cells (Cherry and Glucksmann, 1959; Glucksmann and Cherry, 1962; Dreizen et al , 1976; Stern et al , 1976).…”

Section: Introductionmentioning

confidence: 99%

The enigmatic mechanism of irradiation‐induced damage to the major salivary glands

2002

Oral Diseases

125

106

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Irradiation is a central treatment modality administered for head and neck malignancies. Its major and most devastating side-effect is an induced damage to the major salivary glands. This article aims at suggesting a comprehensive explanation for the underlying mechanism of this damage, which has been considered as enigmatic throughout the 90 years since it was first described in 1911. The mechanism suggested is based on the considerable literature concerning this enigma in rat salivary glands. According to this proposed mechanism, the irradiation results in a sublethal DNA damage, which manifests and becomes lethal at a delayed phase. Thus, when the acinar progenitor cells are going through a reproductive phase when parenchylmal replenishment is required, they die. The injurious agents, which result in this delayed reproductive cell death, appear to be highly redox-active transition metal ions, such as iron and copper. These metal ions, which seem to be associated with secretion granules, are not necessarily contained within the granules as previously suggested, but rather are probably located at sites more proximal to the DNA.

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“…In 2 other studies, long-term parotid function was partially protected against irradiation by the preirradiation administration of desferoxamine (Zn DFO), a very potent intracellular chelator of iron, and also by the antioxidant enzyme manganese superoxide dismutase (MnSOD). 7,8 The potential role of antioxidants in protecting salivary glands is supported by the work of Funegard et al 9 The authors showed that preirradiation administration of alpha tocopherol and beta carotene, the antioxidant vitamins, reduced the adverse effects of irradiation on the salivary glands of rats. Furthermore, in different human double-blind, placebo-controlled, randomized phase 3 trials, it was shown that the radical scavenger amifostine reduced both acute and chronic postirradiation xerostomia.…”

Section: Promentioning

confidence: 60%

“…The parotid glands normally contribute only about 20% of the total volume of unstimulated saliva, whereas the submandibular salivary glands contribute 65% and the sublingual salivary glands 7% to 8%. 8,9 At high flow rates during mastication, the parotid becomes the dominant gland, contributing about 50% of the whole saliva. 8 However, we believe that the unstimulated saliva (resting state) is far more important in the subjective feeling of xerostomia.…”

Section: Chemopreventionmentioning

confidence: 99%

Prophylactic Treatment Reduces the Severity of Xerostomia Following Radiation Therapy for Oral Cavity Cancer

Nagler¹,

Baum²

2003

Arch Otolaryngol Head Neck Surg

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Rat Salivary Gland Function after Fractionated Irradiation

Cited by 10 publications

References 31 publications

Early to late sparing of radiation damage to the parotid gland by adrenergic and muscarinic receptor agonists

Early to late sparing of radiation damage to the parotid gland by adrenergic and muscarinic receptor agonists

The enigmatic mechanism of irradiation‐induced damage to the major salivary glands

Prophylactic Treatment Reduces the Severity of Xerostomia Following Radiation Therapy for Oral Cavity Cancer

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