Preservation of the rat parotid gland function after radiation by prophylactic pilocarpine treatment: Radiation dose dependency and compensatory mechanisms

Purpose: To study the ability of a prophylactic pilocarpine administration to preserve the rat parotid gland function after unilateral irradiation wit h graded doses of X-rays. Methods: The right parotid gland of male albino Wistar rats was irradiated with single doses of X-rays (10-30 Gy, at 1.5 Gy min(-1)). Pilocarpine (4 m g/kg) was administered intraperitoneally, 1 hour prior to irradiation. Sali va samples of both left and right parotid gland were collected by means of miniaturized Lashley cups 4 days before and 3, 7, 10, and 30 days after irr adiation. The parotid salivary flow rate (mu l/min) was used as a parameter for the assessment of parotid gland function. Results: Our data confirm that a single prophylactic treatment of pilocarpi ne can attenuate radiation-induced loss of gland function. Surprisingly, th e effect of pilocarpine was not restricted to the irradiated gland only. Pi locarpine also enhanced the how rate in the contralateral, nonirradiated gl and. The latter effect was found for all doses above 10 Gy and became appar ent around 7 days after the radiation treatment. The effectiveness of piloc arpine to attenuate function loss in the irradiated gland decreased with in creasing dose and was lost after single doses of 30 Gy. Conclusions: Our data provide direct evidence that increasing the compensat ory potential of the nondamaged gland, at least in part, underlies the "rad ioprotective effect" of pilocarpine in case of unilateral radiation. The ab ility of pilocarpine to ameliorate the early radiation-induced impairment o f the parotid gland function in the irradiated gland may therefore be depen dent on the remaining number of functional cells, and thus on the volume of the gland that lies within the radiation portal. (C) 1999 Elsevier Science Inc.