Dataset Information

Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice.

ABSTRACT:

Objectives

One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO) to restore the secretory function of radiation-damaged salivary glands in mice.

Methods

DFO (50 mg/kg/d) was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy) of submandibular glands. The total 55 mice were randomly divided into: (1) Normal group: mice received no treatment (n?=?5); (2) Irradiation group (IR): mice only received irradiation (n?=?5); (3) Pre-DFO group (D+IR) (n?=?10); (4) Pre+Post DFO group (D+IR+D) (n?=?10); (5) Post-DFO group (IR+D) (n?=?10); (6) For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved) for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n?=?5); sham2: Pre+Post sterilized water group (n?=?5); sham3: Post-sterilized water group (n?=?5). The salivary flow rate (SFR) was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.

Results

The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1? and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR.

Conclusions

Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells.

SUBMITTER: Zhang J

PROVIDER: S-EPMC4245233 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice.

Zhang Junye J Cui Lei L Xu Minhua M Zheng Yuanli Y

PloS one 20141126 11

<h4>Objectives</h4>One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO) to restore the secretory function of radiation-damaged salivary glands in mice.<h4>Methods</h4>DFO (50 mg/kg/d) was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy) of submandibular glands. Th ...[more]

PMID: 25427160

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Project description:PurposeDry eye syndrome is a multifactorial chronic disabling disease mainly caused by the functional disruptions in the lacrimal gland. The treatment involves palliation like ocular surface lubrication and rehydration. Cell therapy involving replacement of the gland is a promising alternative for providing long-term relief to patients. This study aimed to establish functionally competent lacrimal gland cultures in-vitro and explore the presence of stem cells in the native gland and the established in-vitro cultures.MethodsFresh human lacrimal gland from patients undergoing exenteration was harvested for cultures after IRB approval. The freshly isolated cells were evaluated by flow cytometry for expression of stem cell markers ABCG2, high ALDH1 levels and c-kit. Cultures were established on Matrigel, collagen and HAM and the cultured cells evaluated for the presence of stem cell markers and differentiating markers of epithelial (E-cadherin, EpCAM), mesenchymal (Vimentin, CD90) and myofibroblastic (?-SMA, S-100) origin by flow cytometry and immunocytochemistry. The conditioned media was tested for secretory proteins (scIgA, lactoferrin, lysozyme) post carbachol (100 µM) stimulation by ELISA.ResultsNative human lacrimal gland expressed ABCG2 (mean±SEM: 3.1±0.61%), high ALDH1 (3.8±1.26%) and c-kit (6.7±2.0%). Lacrimal gland cultures formed a monolayer, in order of preference on Matrigel, collagen and HAM within 15-20 days, containing a heterogeneous population of stem-like and differentiated cells. The epithelial cells formed 'spherules' with duct like connections, suggestive of ductal origin. The levels of scIgA (47.43 to 61.56 ng/ml), lysozyme (24.36 to 144.74 ng/ml) and lactoferrin (32.45 to 40.31 ng/ml) in the conditioned media were significantly higher than the negative controls (p<0.05 for all comparisons).ConclusionThe study reports the novel finding of establishing functionally competent human lacrimal gland cultures in-vitro. It also provides preliminary data on the presence of stem cells and duct-like cells in the fresh and in-vitro cultured human lacrimal gland. These significant findings could pave way for cell therapy in future.

Dataset Information

Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice.

Objectives

Methods

Results

Conclusions

Publications

Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice.

Similar Datasets

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