Calcium Montmorillonite for the Mitigation of Aflatoxicosis and Gastrointestinal Inflammation

Clays have been used for centuries as ‘ancient medicine’ for their therapeutic benefits. One particular clay, calcium montmorillonite, has historically been used as an anti-caking agent in animal feeds, but has also demonstrated the ability to bind toxins and alleviate infectious diarrhea. The full breadth of therapeutic applications and molecular mechanisms of montmorillonite is still unknown. Therefore, the purpose of this research was to explore novel therapeutic applications for NovaSil (NS), a calcium montmorillonite clay to reduce the risk of aflatoxicosis in farm-raised fish and alleviate gastrointestinal inflammation and dysbiosis in a mouse model of Crohn’s disease (CD). Aflatoxin B_(1) (AFB_(1)) is a fungal mycotoxin that commonly contaminates corn and peanut crops. It is produced by the fungi Aspergillus flavus and A. parasiticus during times of drought or due to improper post-harvest storage. Aflatoxin B_(1) is known to cause hepatocellular carcinoma, immunosuppression and growth stunting in several species. Recently, incorporation of plant-based alternatives into feed for farm-raised fish has become a trend, thereby increasing the risk for mycotoxin contamination. Inexpensive strategies to reduce AFB_(1) exposure are needed. Calcium montmorillonite clay, which is both inexpensive and abundant, has a dioctahedral structure that is known to sequester AFB_(1) in its negatively-charged interlayer, thereby reducing systemic bioavailability. There is also some evidence to suggest that calcium montmorillonite clays may possess gastrointestinal anti-inflammatory properties. NovaSil was used as a strategy to reduce the effects of AFB_(1) in Nile tilapia (Oreochromis niloticus) and red drum (Scieanops ocellatus). Juvenile tilapia and red drum were dosed with AFB_(1) and NS over the course of 10 and 7 weeks, respectively. Additionally, proinflammatory cytokine-clay binding was characterized using isothermal analysis, X-ray diffraction (XRD) and transmission electron microscopy (TEM). Furthermore, a TNBS (2,4,6-Trinitrobenzenesulfonic acid)-colitis gastrointestinal mouse model was employed to study the anti-inflammatory properties of NS and its ability to protect the gut microbiome. Results suggest that NS can prevent aflatoxicosis in red drum at a 2% inclusion level over the course of 7 weeks. NovaSil also prevented some toxicity in Nile tilapia; however, these results were not significant. In vitro results also indicate that NS sorbs proinflammatory cytokines such as TNFα and IL-1β in its interlayers. Additionally, NS was found to reduce serum pro-inflammatory cytokine levels in TNBS-induced mice and reduce gut dysbiosis. These results could positively impact both human and animal populations with AFB_(1) exposure and/or chronic gastrointestinal inflammation

The Effect of Aflatoxin-B1 on Red Drum (Sciaenops ocellatus) and Assessment of Dietary Supplementation of NovaSil for the Prevention of Aflatoxicosis

Aflatoxin B1 (AFB1) is a potent carcinogen that causes growth stunting, immunosuppression and liver cancer in multiple species. The recent trend of replacing fishmeal with plant-based proteins in fish feed has amplified the AFB1 exposure risk in farm-raised fish. NovaSil (NS), a calcium montmorillonite clay, has previously been shown to reduce AFB1 bioavailability safely and efficaciously in several mammalian species. This study was designed to: (1) evaluate AFB1 impact on cultured red drum, Sciaenops ocellatus, over the course of seven weeks; and (2) assess NS supplementation as a strategy to prevent aflatoxicosis. Fish were fed diets containing 0, 0.1, 0.25, 0.5, 1, 2, 3, or 5 ppm AFB1. Two additional treatment groups were fed either 5 ppm AFB1 + 1% NS or 5 ppm AFB1 + 2% NS. Aflatoxin B1 negatively impacted red drum weight gain, survival, feed efficiency, serum lysozyme concentration, hepatosomatic index (HSI), whole-body lipid levels, liver histopathological scoring, as well as trypsin inhibition. NovaSil inclusion in AFB1-contaminated diets improved weight gain, feed efficiency, serum lysozyme concentration, muscle somatic index, and intraperitoneal fat ratios compared to AFB1-treated fish. Although not significant, NS reduced AFB1-induced histopathological changes in the liver and decreased Proliferating Cell Nuclear Antigen (PCNA) staining. Importantly, NS supplementation improved overall health of AFB1-exposed red drum

Ozone Inhalation Impairs Coronary Artery Dilation via Intracellular Oxidative Stress: Evidence for Serum-Borne Factors as Drivers of Systemic Toxicity

Photograph used for a newspaper owned by the Oklahoma Publishing Company. Caption: "(Photo of a man on a service truck swepping of the service bed, trash in the background, and more.)

Serum autoantibodies and exploratory molecular pathways in rural miners: A pilot study

Introduction: The Southwestern United States (SWUS) has an extensive history of coal and metal mining, including uranium (U) mining. Lung diseases, including but not limited to, lung cancer and pulmonary fibrosis, have been studied extensively in miners due to occupational, dust-related exposures. However, high-throughput autoimmune biomarkers are largely understudied in miners, despite the fact that ore miners, such as U-miners, are at an increased risk for the development of autoimmune diseases such as systemic sclerosis and systemic lupus erythematosus (SLE). Additionally, there are current gaps in knowledge regarding which signaling pathways may play a role in occupational exposure-associated autoimmunity. Methods: Most current and former miners in the SWUS live close to their previous workplaces, in remote areas, with limited access to healthcare. In this pilot study, by leveraging a mobile clinical platform for patient care and clinical outreach, we recruited 44 miners who self-identified as either U (n = 10) or non-U miners (n = 34) and received health screenings. Serum IgG and IgM autoantibodies against 128 antigens were assessed using a high-throughput molecular technique, as a preliminary health screening opportunity. Results: Even when adjusting for age as a covariate, there was a significant (p < 0.05) association between self-reported U-mining exposure and biomarkers including IgM alpha-actinin, histones H2B, and H4, myeloperoxidase (MPO) and myelin basic protein. However, adjusting for age did not result in significant associations for IgG autoantibody production in U-miners. Bioinformatic pathway analysis revealed several altered signaling pathways between IgM and IgG autoantibodies among both U and non-U miners. Conclusions: Further research is warranted regarding the mechanistic connection between U-exposure and autoantibody development, especially regarding histone-related alterations and IgM autoantibody production