Abstract
BackgroundIn this study the effect of myenteric denervation induced by benzalconium chloride (BAC) on distribution of fibrillar components of extracellular matrix (ECM) and inflammatory cells was investigated in gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rats were divided in four experimental groups: non-denervated (I) and denervated stomach (II) without MNNG treatment; non-denervated (III) and denervated stomachs (IV) treated with MNNG. For histopathological, histochemical and stereological analysis, sections of gastric fragments were stained with Hematoxylin-Eosin, Picrosirius-Hematoxylin, Gomori reticulin, Weigert's Resorcin-Fuchsin, Toluidine Blue and Alcian-Blue/Safranin (AB-SAF).ResultsBAC denervation causes an increase in the frequency of reticular and elastic fibers in the denervated (group II) compared to the non-denervated stomachs (group I). The treatment of the animals with MNNG induced the development of adenocarcinomas in non-denervated and denervated stomachs (groups III and IV, respectively) with a notable increase in the relative volume of the stroma, the frequency of reticular fibers and the inflammatory infiltrate that was more intense in group IV. An increase in the frequency of elastic fibers was observed in adenocarcinomas of denervated (group IV) compared to the non-denervated stomachs (group III) that showed degradation of these fibers. The development of lesions (groups III and IV) was also associated with an increase in the mast cell population, especially AB and AB-SAF positives, the latter mainly in the denervated group IV.ConclusionsThe results show a strong association in the morphological alteration of the ECM fibrillar components, the increased density of mast cells and the development of tumors induced by MNNG in the non-denervated rat stomach or denervated by BAC. This suggests that the study of extracellular and intracellular components of tumor microenvironment contributes to understanding of tumor biology by action of myenteric denervation.
Highlights
In this study the effect of myenteric denervation induced by benzalconium chloride (BAC) on distribution of fibrillar components of extracellular matrix (ECM) and inflammatory cells was investigated in gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
Non-denervated and denervated stomachs treated with MNNG presented changes in tissue architecture and arrangement of the fibers of the extracellular matrix and an increase of the diameter of pyloric glands as well as in relative volume of the stroma (Fig. 1C, D, G and 1H)
Animals with denervated stomachs and treated with MNNG developed precancerous lesions and malign tumors characterized by dysplasia, atrophic gastritis and adenocarcinoma (Fig. 1D and 1H)
Summary
In this study the effect of myenteric denervation induced by benzalconium chloride (BAC) on distribution of fibrillar components of extracellular matrix (ECM) and inflammatory cells was investigated in gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The ENS importance for the regulation of the gastrointestinal functions is observed after the topical application of the cationic surfactant, benzalkonium chloride (BAC), on the serous layer that results in partial and selective destruction of myenteric plexus neurons [6]. The correlation between carcinogenesis and the ENS has been demonstrated in experimental models using the myenteric denervation by BAC and the induction of tumors by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) [7] and 1,2-dimethylhydrazine (DMH) [8] with a reduction in the incidence and size of gastrointestinal tumors
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