An Experimental Study on Botulinum Toxin Type A for the Treatment of Excessive Secretion after Submandibular Gland Transplantation in Rabbits

Abstract

Objectives. To investigate whether botulinum toxin type A (BTXA) could control excessive secretion after submandibular gland (SMG) transplantation in rabbits and its possible mechanisms. Methods. A new SMG transplantation model was established in rabbit. 30 successfully constructed models were randomly assigned to five groups including control group and four experimental groups. Secretion outputs were used to analyze the effect of BTXA injection on excessive secretion. Hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), Western blot, and immunofluorescence were performed to analyze its possible mechanisms. Results. After BTXA injection, a significant decrease of excessive secretion after SMG transplantation was found in 2 and 4 weeks groups, but no significant effect on 12 and 24 weeks groups. HE and TEM results showed that BTXA led to morphological and ultrastructural changes of acinar cells of transplanted SMG. Western blot results suggested that BTXA decreased the aquaporin-5 (AQP5) protein expression after BTXA injection for 2 and 4 weeks. Immunofluorescence results showed that AQP5 protein was mainly expressed in the cytoplasm after BTXA injection for 2 and 4 weeks, which might indicate that BTXA promoted AQP5 expression from the cell membrane to cytoplasm. Conclusion. BTXA could effectively control excessive secretion after SMG transplantation in rabbits.

Effects of chronic treatment with botulinum toxin type A in salivary glands of rats: Histological and immunohistochemical analyses

“…The absence of acetylcholine in synapses causes functional chemical denervation, preventing salivary secretion . BoNT‐A also showed water transport system interference in glandular cells by decreasing the availability of aquaporin‐5 channels in submandibular rabbit glands …”

“…6 BoNT-A also showed water transport system interference in glandular cells by decreasing the availability of aquaporin-5 channels in submandibular rabbit glands. 7 Decrease in glandular volume, acinar, and ductal cell counts have been reported as among morphological effects after intraglandular application of BoNT-A. 8 Studies regarding the treatment effects with repeated applications of BoNT-A in salivary glands are limited.…”

Autonomic reinnervation and functional regeneration in autologous transplanted submandibular glands in patients with severe keratoconjunctivitis sicca

“…Moreover, botulinum neurotoxin A (BTXA) inhibits acetylcholine release by binding to an acceptor protein on the presynaptic membrane of the acetylcholine nerve terminal. 32 It has been reported that BTXA was effective in reducing the secretion of the transplanted SMG in patients 33 and rabbits, 34 , 35 which provided additional evidences for the functional reinnervation of the cholinergic nerves in transplanted SMG.…”

The histologic effects of high doses of botulinum toxin a on the rabbit's salivary gland

“…Clinically, botulinum toxin A (neurotoxic protein) has been utilized to manage the increase in the salivary gland secretion, but the exact mechanism of this agent on this gland regarding its function and histology remains unclear (1). In fact, clostridium botulinum bacteria are the source of Botulinum toxin A which was used also in cases of excessive lacrimation, drooling, and hyperhidrosis (2,3). The action of Botulinum toxin A is depending on the inhibitory effect on acetylcholine release at the presynaptic region, as it acts on the parasympathetic nerve terminals (cholinergic nerve terminals) which lead to localized chemical block with neuronal activity loss in the target tissue (4).…”