Prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by X-ray irradiation in rats.
1. In the present study, we investigated the prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by either single (15 Gy) or repeated (8.6 Gy x3 days) X-ray irradiation in rats. Pilocarpine hydrochloride was administered orally 90 min before each irradiation session. Then, 7 days later, salivary volume, amylase activity and protein concentration in the saliva secreted from the right parotid gland were measured before and after a subsequent administration of pilocarpine hydrochloride (intraduodenal). 2. In irradiated no-pretreatment rats, irradiation induced a significant reduction in both spontaneous and pilocarpine hydrochloride-stimulated secretion (both total salivary volume and flow rate), regardless of the protocol used for X-ray exposure. In irradiated, pilocarpine hydrochloride-pretreated rats, salivary secretion was increased after stimulation by pilocarpine hydrochloride (intraduodenal) to a degree that depended on the pretreatment dose of pilocarpine hydrochloride (p.o.) in both xerostomia models. 3. There were no differences in amylase or protein concentrations between irradiated rats pretreated with pilocarpine hydrochloride and irradiated no-pretreatment control rats. 4. A decrease in the weight of the parotid gland was observed in rats exposed to either the single dose or repeated irradiation protocols. Changes in the submandibular gland were less marked than those in the parotid gland. These changes in gland weight were not affected by pilocarpine hydrochloride pretreatment. 5. The responsiveness of the parotid gland to subsequent stimulation with pilocarpine hydrochloride was apparently preserved in both xerostomia models by pretreatment with pilocarpine hydrochloride, which itself increased salivary secretion. This suggests that pilocarpine hydrochloride may exert functional protective effects against xerostomia that occurs following irradiation therapy through a stimulation of salivary secretion.
Asari
T
T
Pharmacology Research and Discovery Research, R&D, Kissei Pharmaceutical Co. Ltd, 4365-1 Kashiwabara, Hotaka, Minamiazumi, Nagano Prefecture 399-8304, Japan. tetsuya_asari@pharm.kissei.co.jp
Komatsu
Y
Y
Misawa
K
K
Hara
K
K
Akahane
M
M
D000818:Animals; D008297:Male; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D010862:Pilocarpine / Q000008:administration & dosage / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D012463:Saliva / Q000378:metabolism; D014965:X-Rays; D014987:Xerostomia / Q000000981:diagnostic imaging / Q000517:prevention & control*
D018721:Muscarinic Agonists; D010862:Pilocarpine