Intraglandular application of botulinum toxin leads to structural and functional changes in rat acinar cells.
OBJECTIVE
Intraglandular injection of botulinum toxin (BoNT) leads to a transient denervation of the submandibular gland and this is associated with reduced salivary secretion. The purpose of the present study was to verify whether temporary acinar atrophy occurs simultaneously with chemical denervation of the glands.


METHODS
Tissue specimens of the right submandibular gland taken from 18 Wistar rats after intraglandular injection of BoNT A, BoNT B, or a combination of both were examined. As a sham control, an equivalent volume of saline was injected into the left submandibular gland. Morphometric measurements, immunohistochemistry, electron microscopy and western blot analysis were used to analyse the morphological and functional changes of the denervated glands.


RESULTS
Morphological and ultrastructural analyses of the cell organelles and secretory granula showed a clear atrophy of the acini, which was more prominent in glands injected with the combination of BoNT/A and B. Morphometric measurements of the glandular acini revealed a significant reduction of the area of the acinar cells after injection of BoNT (P=0.031). The expression of amylase was significantly reduced in BoNT treated glands.


CONCLUSIONS
Intraglandular application of BoNT induces structural and functional changes of the salivary glands indicated by glandular atrophy. These effects may be due to glandular denervation induced by the inhibition of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs) involved in acetylcholine release at the neuroglandular junction and also specially inhibition of those involved in exocytosis of the granula of the acinar cells.
Teymoortash
A
A
Department of Otolaryngology-Head and Neck Surgery, Philipp University, Deutschhausstrasse 4, Marburg 35037, Germany. teymoort@med.uni-marburg.de
Sommer
F
F
Mandic
R
R
Schulz
S
S
Bette
M
M
Aumüller
G
G
Werner
J A
JA
D000681:Amylases / Q000032:analysis; D000818:Animals; D001284:Atrophy; D001905:Botulinum Toxins / Q000633:toxicity*; D019274:Botulinum Toxins, Type A / Q000633:toxicity*; D048429:Cell Size; D008297:Male; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D017764:Parasympathectomy; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013363:Submandibular Gland / Q000187:drug effects* / Q000201:enzymology / Q000294:innervation / Q000648:ultrastructure
C096323:rimabotulinumtoxinB; D000681:Amylases; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A