Pilocarpine improves submandibular gland dysfunction in irradiated rats by downregulating the tight junction protein claudin-4

Objectives: To investigate the effects of radiation on paracellular pathway of rat submandibular glands (SMGs) and the mechanism of increasing secretion following treatment with pilocarpine.

Materials and methods: In situ irradiation models of SMGs in Wistar rats were conducted, and the glands were exposed to X-radiation at a single dose of 20 Gy. Pilocarpine was intraperitoneally injected 60 min prior to radiation and continuous 6 days postirradiation for a total of 7 days. Salivary secretion, histological changes, pro-inflammatory cytokines, alterations in tight junctions (TJs), and functional membrane proteins aquaporin-5 (AQP5) and claudin-4 mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 weeks after irradiation.

Results: Salivary secretion of the irradiated glands was reduced at 1 and 12 weeks. As well, acinar cell numbers, TJ width, and the levels of M3 receptor and AQP5 were decreased. In contrast, tumor necrosis factor-α, interleukin 6, interleukin 1α, and the expression of the TJ protein claudin-4 were significantly increased in irradiated SMGs. Notably, all the alterations were attenuated by pilocarpine treatment.

Conclusions: Pilocarpine could improve the secretory function of irradiated rat SMGs via reducing inflammation, ameliorating the structural injury of TJs, and attenuating the up-regulation of claudin-4 expression.