Optimum dose range for the amelioration of long term radiation-induced hyposalivation using prophylactic pilocarpine treatment

Burlage, Fred Ronald; Roesink, Judith M.; Faber, Hette; Vissink, Arjan; Langendijk, Johannes A.; Kampinga, Harm H.; Coppes, Rob P.

doi:10.1016/j.radonc.2007.10.011

« Previous Next »Radiotherapy & Oncology
Volume 86, Issue 3 , Pages 347-353, March 2008

Optimum dose range for the amelioration of long term radiation-induced hyposalivation using prophylactic pilocarpine treatment

Fred Ronald Burlage
- Department of Radiation Oncology, University of Groningen, The Netherlands
- Corresponding author. Fred Ronald Burlage, Department of Radiation Oncology, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
- These authors contributed equally.
Judith M. Roesink
- Department of Radiotherapy, University Hospital Utrecht, The Netherlands
- These authors contributed equally.
Hette Faber
- Department of Radiation Oncology, University of Groningen, The Netherlands
- Department of Cell Biology, University of Groningen, The Netherlands
Arjan Vissink
- Department of Oral and Maxillofacial Surgery, University of Groningen, The Netherlands
Johannes A. Langendijk
- Department of Radiation Oncology, University of Groningen, The Netherlands
Harm H. Kampinga
- Department of Cell Biology, University of Groningen, The Netherlands
Rob P. Coppes
- Department of Radiation Oncology, University of Groningen, The Netherlands
- Department of Cell Biology, University of Groningen, The Netherlands

Received 25 July 2007; received in revised form 5 October 2007; accepted 11 October 2007. published online 16 November 2007.

Abstract

Background

To determine dose and time dependency of pilocarpine pre-treatment protection from late damage after unilateral irradiation of the rat parotid gland.

Methods and materials

The right parotid gland of saline (1mg/ml) or pilocarpine (4mg/kg) pre-treated rats was irradiated with 10, 15 and 20Gy. Saliva was collected from the irradiated and shielded parotid before, 30, 60, 120 and 240 days after irradiation. The number of acinar cells/gland was determined 30, 120 and 240 days after irradiation by histological examination.

Results

Pilocarpine pre-treated rats, protection of parotid gland function was seen in the early-intermediate phase (0–120 days) after 15Gy and in the late phase (>120 days) after 10 and 15Gy. Although no protection was observed after 20Gy, a stimulatory effect of pilocarpine on the non-irradiated gland resulted in a significant increase in total saliva secretion.

The increase in function after pilocarpine treatment was paralleled by a significant increase in the number of acinar cells in both the irradiated and shielded glands.

Conclusions

Pre-irradiation treatment with pilocarpine induces compensatory response, at lower doses, in the irradiated and at higher doses in the non-irradiated gland reducing late damage, due to stimulation of unirradiated or surviving cells to divide.

Keywords: Pilocarpine, Parotid gland, Radiation-induced damage, Radioprotection