Research Article: Botulinum toxin as a treatment for short bowel syndrome in rats1

Date Published: September 16, 2019

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia

Author(s): Isabela Cristina de Souza Marques, Stefânia Bovo Minto, Mariane Quaglio Marques, Juliana Ribeiro, Paola Castro Moraes, Lourenço Sbragia, Sérgio Britto Garcia.

http://doi.org/10.1590/s0102-865020190070000005

Abstract

The denervation of the intestine with benzalkonium chloride (BAC) reduces mortality and improves weight gain in rats with short bowel syndrome (SBS). Nevertheless, translating these promising findings from bench to bedside is not feasible because BAC promotes peritonitis and irreversible denervation which may be followed by an uncontrolled dilatation of the viscera. The use of botulinum toxin (BT) instead of BAC to achieve the denervation of the remaining small intestine in SBS could be an interesting option because it leads to a mild and transient denervation of the intestine.

Here we evaluated the effects of the ileal denervation with BT in rats with SBS by verifying the body weight variation and intestinal morphological parameters. Four groups with 6 animals each were submitted to enterectomy with an ileal injection of saline (group E) or BT (group EBT). Control groups were submitted to simulated surgery with an ileal injection of BT (group BT) or saline (group C – control).

We observed that the treatment of the remaining ileum with BT completely reversed the weight loss associated to extensive small bowel resection.

This may provide a new promising approach to the surgical treatment of SBS.

Partial Text

Short bowel syndrome (SBS) is an intestinal failure resulting from an insufficient absorption surface of the intestine, usually due to surgical removal of more than 50% of the intestine length. The hallmark symptoms of the SBS are malnutrition and weight loss. Parenteral nutrition, as well as several clinical and surgical procedures have been used on the patients with SBS and in experimental settings. Nevertheless, only limited success has been achieved so far. In fact, morbidity and mortality rates remain disappointedly high in patients with SBS. “The development of new and innovate therapy designed to amplify the intestinal adaptation after extensive resections is required to improve and save human life” has been proposed by Longshore, in 20091. In regard to this, it has been observed that the myenteric denervation of the remaining small intestine was able to reduce mortality in rats with SBS2. In sequence we have confirmed these findings and described that the clinical improvements were due to a massive increase of the intestinal absorptive surface in rats with SBS with the BAC denervation3. We have also found similar results with the denervation of the jejunum4. The effects of BAC denervation in SBS were further confirmed by other authors5. Nevertheless, despite the encouraging preliminary results and the usefulness of the BAC experimental model for the comprehension of the role of the enteric nervous system in intestinal adaptations after extensive resections, translating these promising findings from bench to bedside is not yet a feasible task. In fact, it would be reckless to perform such experiments in humans because BAC promotes peritonitis with further risk of pseudo-obstruction, as well as irreversible denervation followed by uncontrolled dilatation of the viscera6. In this aspect the use of botulinum toxin (BT) instead of BAC as a way of achieving the denervation of the remaining small intestine in SBS could be an interesting option because it leads to a mild and transient denervation of the intestine7. Here, we evaluated the effects of the ileal denervation with BT in rats with SBS by verifying the body weight variation and intestinal morphological parameters.

The study was approved by an institutional ethics committee for animal experimentation (Protocol 016529/2017 – UNESP).

No differences in food intake were observed among the experimental groups, and at the end of the experimental period all the animals were healthy. Both the surgical procedures and the BT injections were well tolerated, and no side effects were seen in the animals. At the end of the experimental period, the group E, that underwent an enterectomy, presented marked weight loss (P<0.05). Interestingly, the EBT group showed an increase in weight similar to that of the control animals (Fig. 1). We observed in all the operated animals that the treatment of the remaining ileum with BT completely reversed the weight loss associated to extensive small bowel resection. The present findings are similar to previous reports in the literature regarding the beneficial effects of denervation with benzalkonium chloride in rats submitted to experimental SBS3,4. The botulinum toxin application may provide a new promising approach to the surgical treatment of SBS.   Source: http://doi.org/10.1590/s0102-865020190070000005

 

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