Radioprotective effect of lidocaine on neurotransmitter agonist-induced secretion in irradiated salivary glands.

Previously we verified the radioprotective effect of lidocaine on the function and ultrastructure of salivary glands in rabbits. However, the underlying mechanism of lidocaine's radioprotective effect is unknown. We hypothesized that lidocaine, as a membrane stabilization agent, has a protective effect on intracellular neuroreceptor-mediated signaling and hence can help preserve the secretory function of salivary glands during radiotherapy. Rabbits were irradiated with or without pretreatment with lidocaine before receiving fractionated radiation to a total dose of 35 Gy. Sialoscintigraphy and saliva total protein assay were performed before radiation and 1 week after the last radiation fraction. Isolated salivary gland acini were stimulated with either carbachol or adrenaline. Ca(2+) influx in response to the stimulation with these agonists was measured using laser scanning confocal microscopy. The uptake of activity and the excretion fraction of the parotid glands were significantly reduced after radiation, but lidocaine had a protective effect. Saliva total protein concentration was not altered after radiation. For isolated acini, Ca(2+) influx in response to stimulation with carbachol, but not adrenaline, was impaired after irradiation; lidocaine pretreatment attenuated this effect. Lidocaine has a radioprotective effect on the capacity of muscarinic agonist-induced water secretion in irradiated salivary glands

Scintigraphic results of parotid glands before and one week after irradiation.

<p>(A) Uptake index. (B) Ejection fraction.</p

Confocal microscopic view of isolated acini loaded with Fluo-4 AM.

<p>(A) Before carbachol stimulation; (B) After carbachol stimulation.</p

Effects on tissue ultrastructure examined by transmission electron microscopy.

<p>(A) Normal basolateral membrane in the control group (arrow). (B) In the irradiated/sham-treated group, thickening and irregular plump formations of basolateral membrane were observed (arrow). (C) In the irradiated/lidocaine-pretreated group, no obvious basolateral membrane alteration was observed (arrow).</p

Saliva total protein concentration before and one week after irradiation.

<p>Saliva total protein concentration before and one week after irradiation.</p

Confocal microscopic study of fluorescence alteration before and after carbachol stimulation of the acini.

<p>(A-C) Rabbit No. 3 in the control group; (D-F) Rabbit No. 3 in the irradiated/sham-treated group. (G-I) Rabbit No. 3 in the irradiated/lidocaine-pretreated group. (A, D and G) Laser scanning confocal microscopic views of regions of interest before stimulation. (B, E and H) Laser scanning confocal microscopic views of regions of interest after stimulation. (C, F and I) Quantitative dynamic analysis of fluorescence. Cch: carbachol.</p