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

Regueira, Luciana Silva; Baratella-Evêncio, Liriane; Oliveira, Jaciel Benedito de; Silva, Priscilla Suelen Oliveira Carvalho da; Valença, Gabriela Andrade Lima; Conceição, Juliana Cristina Peixoto; Perez, Danyel Elias da Cruz

doi:10.1111/jop.12887

Cited by 12 publications

(16 citation statements)

References 18 publications

(27 reference statements)

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“…Interestingly, the strong PSMA radioligand accumulation in salivary glands does not correspond to high PSMA expression levels in the glands, indicating unspecific PSMA radioligand uptake into SG [19]. BTX-A induces reversible cellular changes in salivary glands with decreased mucosal and serous acini diameter and temporary glandular atrophy [8,20]. These effects are probably due to fully reversible glandular denervation resulting in reduced radiation sensitivity [20].…”

Section: Discussionmentioning

confidence: 99%

“…BTX reduces salivary gland activity in a dose-dependent manner with subsequent and fully reversible ductal and acinar apoptosis [7,8]. However, in a preliminary case series with regular-dose IncoA distributed across the submandibular and parotid glands we observed no reduction of Lutetium-144-PSMA (Lu-PSMA) radioligand uptake in any of the injected glands.…”

Section: Introductionmentioning

confidence: 87%

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Safety of High-Dose Botulinum Toxin Injections for Parotid and Submandibular Gland Radioprotection

Mueller

Langbein

Mishra

et al. 2022

Toxins

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Botulinum Toxin injections into salivary glands (SG) up to a total dose of 100 units IncobotulinumtoxinA (IncoA) represent the treatment of choice for sialorrhea. However, BTX might also protect SG against sialotoxic radioligand cancer therapies. The radioligand Actinium-225-PSMA effectively targets Prostate Cancer (PCa) metastases but inevitably destroys SG due to unintended gland uptake. A preliminary case series with regular-dose IncoA failed to reduce SG PSMA-radioligand uptake. We therefore increased IncoA dosage in combination with transdermal scopolamine until a clinically relevant SG PSMA-radioligand uptake reduction was achieved. Ten consecutive men with metastasized PCa refractory to all other cancer therapies received gradually increasing IncoA dosages as part of a compassionate use PSMA-radioligand-therapy trial. The parotid gland received six and the submandibular gland three injection points under ultrasound control, up to a maximum of 30 units IncoA per injection point. A maximum total dose of 250 units IncoA was applied with up to 170 units per parotid and 80 units per submandibular gland. Treatment was well tolerated and all side-effects were non-serious. The most frequent side-effect was dry mouth of mild severity. No dysphagia, facial weakness, chewing difficulties or systemic side-effects were observed. SG injections with IncoA up to a total dose of 250 units are safe when distributed among several injection-points under ultrasound control by an experienced physician. These preliminary findings lay the basis for future trials including BTX as major component for SG protection in established as well as newly emerging radioligand cancer therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 87%

Safety of High-Dose Botulinum Toxin Injections for Parotid and Submandibular Gland Radioprotection

Mueller

Langbein

Mishra

et al. 2022

Toxins

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“…On the contrary, a later study documented a decrease in parotid acinar size when injected with 2u of BTX-A [19] , however the authors didn't undergo morphometric analysis. In another study, a decrease in the diameter of acini of submandibular and sublingual glands was documented after being injected with BTX-A of a dose 2.5 u [30] . Nevertheless, the authors applied the injection for three times throughout the experiment.…”

Section: Discussionmentioning

confidence: 93%

Influence of Intramasseteric Injection of Botulinum Toxin Type A on the Ipsilateral Submandibular Salivary Gland of Albino Rats

Hussein

2020

Egyptian Journal of Histology

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Background: Botulinum toxins are used in treating involuntary muscle contraction such as hemifacial spasm and facial nerve palsy, hyperhidrosis or excessive saliva production. Minor side effects are reported like local hematoma, pain, dry mouth and viscous saliva. However; major complications may occur such as loss of motor head control and aspiration pneumonia. Some animal studies showed minimal histological changes. While, some authors have demonstrated significant structural and functional changes in the parotid gland of rats and the submandibular gland of rabbits after being injected with botulinum toxin type-A (BTX-A). Aim of the Study:To evaluate the effect of intramasseteric injection of BTX-A on the ipsilateral submandibular gland in Albino rats. Materials and Methods: Fifty six adult male Albino rats were divided into four groups. Rats of group (I) and group (II) received intramasseteric injection of 0.05 ml or 0.1 ml of 0.9% sodium chloride solution respectively. Rats of group (III) and group (IV) received intra-masseteric injection of 2.5 units or 5 units of BTX-A respectively. Each group was further subdivided into two subgroups according to the time of sacrifice which was at three or fourteen days. Sections of glands were stained by H&E and S100 protein antibody. Results: Glands' acini of group III and IV showed cytoplasmic vacuolations. Acini of group IV at fourteen days showed irregular outline with areas of complete degeneration. Duct system of both groups showed signs of degeneration. Using immunohistochemical staining, group III and IV showed increased area percentage of positive reaction than control groups. Statistical analysis of acini diameter and area percentage of anti-S100 protein revealed significant increase in botox injected subgroups. Conclusion: Intramasseteric injection with BTX-A was able to induce histological changes in submandibular gland of the ipsilateral side.

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“…Currently, there are no cellular or animal disease models of FBS, making the more basic study of the pathophysiology and pharmacologic mechanism of action difficult. However, we postulate BTA may improve resolution of the disease secondary to decreases in salivary gland weight, cholinergic output, secretory capacity, cellular size, and myoepithelial function after injection (74)(75)(76). Additionally, nerve growth factor (NGF) expression can be increased by BTA (77), which may lead to improved parotid gland sympathetic reinnervation (78).…”

Section: Discussionmentioning

confidence: 99%

Botulinum toxin A for the treatment of first bite syndrome—a systematic review

Shaikh¹,

Jafary²,

Behnke³

et al. 2022

Gland Surg

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Background: First bite syndrome (FBS) is a rare post-surgical complication resulting in peri-parotid pain after the first bite of meals. Intra-parotid Botulinum toxin A may offer relief for these symptoms. There is no consensus on the optimal dosage, timing to symptom improvement, need for repeat injections, and safety of this treatment. The objective of this systematic review was to assess the efficacy and safety of intra-parotid Botulinum toxin A injection in treating FBS. Methods: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar were searched from the inception until July 2020. Case reports, case series, prospective and retrospective trials in which patients with post-surgical FBS were treated with intra-parotid botulinum toxin A injection were included. The primary outcome was improvement of FBS symptoms. Secondary outcomes were time to symptom improvement and complications. Risk of bias was assessed with National Institute of Health (NIH) Quality Assessment Tools.Results: Search results yielded 41 studies. Thirty-three articles were excluded after screening titles, abstracts, and full texts, yielding eight studies, from which 22 patients were included. No studies included a control. All studies were of lower quality and had at least moderate risk of bias. The initial botulinum toxin A injection dose ranged from 10-75 U. Time from surgical treatment to injection ranged from 1 month to 3 years. Seven studies, containing 17 patients, reported individual patient outcomes. Clinical improvement was reported in 16 patients lasting between 1-30 months post injection. Eight of 8 (100%) patients receiving at least 40 U botulinum toxin A had symptom improvement. Ten of 22 (45.5%) patients received a second botulinum toxin A injection due to return of pain at a mean of 3.8 months after the first injection. Seven of 22 (38.1%) patients had complete symptom resolution at a mean of 12.1 months. There were no reported injection complications, including: facial paralysis, infection, injection site reaction, and allergic reaction.Discussion: There are no controlled studies comparing intra-parotid botulinum toxin A to observation for FBS. However, botulinum toxin A appears to be a potentially safe, effective treatment.

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

Cited by 12 publications

References 18 publications

Safety of High-Dose Botulinum Toxin Injections for Parotid and Submandibular Gland Radioprotection

Safety of High-Dose Botulinum Toxin Injections for Parotid and Submandibular Gland Radioprotection

Influence of Intramasseteric Injection of Botulinum Toxin Type A on the Ipsilateral Submandibular Salivary Gland of Albino Rats

Botulinum toxin A for the treatment of first bite syndrome—a systematic review

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