Oral exposure to inorganic mercury or methylmercury elicits distinct pro-inflammatory and pro-oxidant intestinal responses in a mouse model system
Introduction
Mercury (Hg) is a toxic heavy metal with a significant impact on the environment and human health, present in various foods at levels exceeding recommended limits due to anthropogenic activities. This metal appears in food mainly as divalent inorganic mercury [Hg(II)], found predominantly in fish products and non-alcoholic beverages, and organic mercury [primarily methylmercury; (MeHg)], which is the main form in fish products. Rice can also be a relevant source of mercury exposure, especially in contaminated areas. Chronic exposure to this metal is significant in some parts of the world and for certain population groups with fish-rich diets.
The toxicity of Hg has been extensively studied, with Hg(II) primarily affecting the kidneys, while the neurological damage caused by MeHg is well documented. Although food is the main vehicle of Hg exposure in humans, and thus the gastrointestinal mucosa is in direct contact with Hg, mercurial toxicity at this level has received little attention. Studies in mammals, mainly rodents, have shown histological alterations in the intestine following oral exposure to Hg, such as shortening of colorectal glands, a decrease in the number of goblet cells, inflammatory effects, and increased apoptosis in the colon. Exposure to Hg(II) showed inflammatory effects and increases in apoptosis in the colon. As for MeHg, studies on its effects in the intestine are even scarcer.
The role of Muc2 in this article
Muc2 is a gene that encodes for mucin-2, a glycoprotein primarily secreted by goblet cells in the colon. Mucin-2 plays a crucial role in the formation and maintenance of the mucus layer that protects the intestinal mucosa. This mucus layer acts as a physical and biochemical barrier, preventing direct contact between microorganisms and the epithelial cells of the intestine. Additionally, it contributes to the lubrication and hydration of the mucosa. Mucin-2 is essential for intestinal homeostasis, protecting against infections and reducing inflammation. Alterations in the production or structure of Muc2 are associated with various intestinal diseases, including ulcerative colitis and irritable bowel syndrome.
In the presented study, exposure to Hg(II) and MeHg significantly affected the expression and abundance of Muc2 in the mouse colon. An upregulation of IL13 and Muc2 was observed in animals treated with the highest concentrations of both mercury species, indicating an increase in mucus secretion in response to exposure to these toxic compounds. However, Western blot analysis only detected a significant increase in MUC2 abundance in mice exposed to MeHg. These findings suggest that mucin-2 might be playing a protective role in the intestine by attempting to compensate for mercury-induced damage. Additionally, exposure to MeHg increased the depth of intestinal crypts and the number of PAS+ cells, indicating higher mucus production, while Hg(II) showed the opposite effect.
A polyclonal antibody for the detection of Muc2 via Western Blot
The presence and increase of MUC2 were confirmed using Western blotting. For this, the anti-MUC2 antibody (ABK1-A6853) from Abyntek Research Reagents was used. The detection of MUC2 demonstrated the toxic effects of methylmercury (MeHg) on mucin production in the colon. The results showed that subchronic exposure to MeHg induces a significant increase in the expression and production of MUC2, which is associated with mucus hypersecretion and hyperplasia of mucus-secreting cells in the colon.
For over 15 years, Abyntek Biopharma has offered advice in numerous research studies to select the most suitable biological reagent to ensure optimal results in the analyzed biomarkers. In addition to sharing their knowledge and experience to support research, the biopharmaceutical company provides a wide range of high-quality products from their Abyntek Research Reagents line, specifically designed to meet the needs of researchers involved in such studies.
Conclusion
This study demonstrates that oral exposure to the two most common species of mercury in food, Hg(II) and MeHg, causes significant intestinal damage. Alterations were observed in intestinal barrier function and adverse effects on components crucial for maintaining intestinal homeostasis. Both species of mercury induce proinflammatory responses and increase oxidative stress, although they exhibit differences in specific toxicity mechanisms and affected markers. The results suggest that mercury exposure may compromise intestinal permeability, facilitating the translocation of bacteria and harmful substances into the immune system, exacerbating chronic inflammation, and possibly contributing to systemic pathologies.
This article was published in Food and Chemical Toxicology, on the 1 of May of 2023
