Search

ABSTRACT: Fluoride is one of the essential trace elements for body. However, excessive fluoride poses a major threat to human and animal health. Fluorosis may cause pathological damage of the duodenum, but the underlying mechanism needs to be further studied. This study was to investigate the effects of long-term exposure to sodium fluoride (0, 500, 1,000, 2,000 mg/kg) on the duodenum of chickens. The results showed that after NaF exposure, intestinal epithelial cells were disarranged, necrotic or even exfoliated, goblet cells and mucus secretion were increased, and inflammatory response was induced in duodenal tissue. Oxidative stress, endoplasmic reticulum stress (ERs), and heat shock proteins (HSPs) are an adaptive response, however long-term, excessive changes are detrimental. Fluorosis activates ERs through IRE1, PERK and ATF6 pathways, increases the expression of HSP60, HSP70 and HSP90, and causes apoptosis and oxidative damage in duodenal tissue. In addition, fluorosis can activate the MAPK signaling pathway. This article can provide a reference for exploring the potential duodenal toxicity of sodium fluoride.

Fluoride is one of the essential trace elements for body. However, excessive fluoride poses a major threat to human and animal health. Fluorosis may cause pathological damage of the duodenum, but the underlying mechanism needs to be further studied. This study was to investigate the effects of long-term exposure to sodium fluoride (0, 500, 1,000, 2,000 mg/kg) on the duodenum of chickens. The results showed that after NaF exposure, intestinal epithelial cells were disarranged, necrotic or even exfoliated, goblet cells and mucus secretion were increased, and inflammatory response was induced in duodenal tissue. Oxidative stress, endoplasmic reticulum stress (ERs), and heat shock proteins (HSPs) are an adaptive response, however long-term, excessive changes are detrimental. Fluorosis activates ERs through IRE1, PERK and ATF6 pathways, increases the expression of HSP60, HSP70 and HSP90, and causes apoptosis and oxidative damage in duodenal tissue. In addition, fluorosis can activate the MAPK signaling pathway. This article can provide a reference for exploring the potential duodenal toxicity of sodium fluoride., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Toxicity dose-response models describe the correlation between dose delivered to an organ and a given toxic endpoint. Duodenal toxicity is a dose limiting factor in the treatment of pancreatic cancer with radiation but the relationship between dose and toxicity in the duodenum is not well understood. While there have been limited studies into duodenal toxicity through investigations of the volume of the organ receiving dose over a specific threshold, both dose-volume and dose-surface histograms lack spatial information about the dose distribution, which may be important in determining normal tissue response. Due to the complex geometry of the duodenum, previous methods for unwrapping tubular organs for spatial modeling of toxicity are insufficient. A geometrically robust method for producing 2D dose surface maps (DSMs), specifically for the duodenum, has been developed and tested in order to characterize the spatial dose distribution. Methods: The organ contour is defined using Delaunay triangulation. The user selects a start and end coordinate in the structure and a path is found by regulating both length and curvature. This path is discretized and rays are cast from each point on the plane normal to the vector between the previous and the next point on the path and the dose at the closest perimeter point recorded. These angular perimeter slices are "unwrapped" from the edge distal to the pancreas to ensure the high dose region (proximal to the tumor) falls in the centre of the dose map. Gamma analysis is used to quantify the robustness of this method and the effect of overlapping planes. Results: This method was used to extract DSMs for 15 duodena, with one esophagus case to illustrate the application to simpler geometries. Visual comparison indicates that a 30×30 map provides sufficient resolution to view gross spatial features of interest. A lookup table is created to store the area (cm²) represented by each pixel in the DSMs in order to allow spatial descriptors in absolute size. The method described in this paper is robust, requires minimal human interaction, has been shown to be generalizable to simpler geometries, and uses readily available commercial software. The difference seen in DSMs due to overlapping planes is large and justifies the need for a solution that removes such planes. Conclusions: This is the first time 2D dose surface maps have been produced for the duodenum and provide spatial dose distribution information which can be explored to create models that may improve toxicity prediction in treatments for locally advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

Copper (Cu) has been widely used in industrial agricultural production, but excess use can lead to toxic effect on host physiology, which poses a threaten to public hygiene. However, the relationship between gut microbiota and Cu-induced intestinal toxicity is unclear. Here, we identified that intestinal flora disturbance was related to duodenal toxicity under Cu exposure. We found that excess Cu disturbed gut microbiota homeostasis, resulting in Cu accumulation and intestinal damage. In addition, Cu considerably increased intestinal permeability by reducing expression of tight junction proteins (Claudlin-1, Occludin, and ZO-1). Meanwhile, Cu could induce endoplasmic reticulum stress, mitophagy, and mitochondria-mediated apoptosis in the duodenum, with the evidence by the elevated levels of GRP78, GRP94, LC3Ⅱ/LC3Ⅰ and Caspase-3 protein expression. Correlation analysis showed that Melainabacteria was closely related to tight junction proteins and endoplasmic reticulum stress of duodenum, indicating that disturbance of intestinal flora may aggravate the toxic effect of Cu. Therefore, our results suggest that the destruction of intestinal flora induced by excessive Cu may further lead to intestinal barrier damage, ultimately leading to endoplasmic reticulum stress, mitophagy and apoptosis. This research provides a new insight into interpretation of the interrelationship between microbiota disorder and duodenal toxicity under Cu exposure. [Display omitted] • Duodenum is the target organ of Cu toxicity. • Cu disturb the duodenal microbiota and increase the potential pathogenicity. • Cu reduce tight junction protein expression and induce Endoplasmic reticulum stress. • Intestinal flora may be involved in the regulation of Cu toxicity to duodenum by regulating mitophagy and apoptosis. [ABSTRACT FROM AUTHOR]