Streptococcal superantigens: biological properties and potential role in disease, in. Consequences of exercise at exhaustion levels include increased number of leukocytes due to the damage of muscle fibers and connective tissue (Morillas-Ruiz and Hernndez-Snchez, 2015) as well as elevated lipid-peroxidation marker MDA in the plasma (Pingitore et al., 2015). Surfactant modified zeolites as a drug-carrier and the release of chloroquin. Still, presented studies provide intriguing data on positive medical effects for this type of materials, especially effects on the immune system and detoxification, all substantiated by so far presented safe profile. PMC legacy view All these documented effects are due to the clinoptilolite capacity to adsorb harmful substances in the gastrointestinal tract that are not confined only to micotoxins and ammonia but include heavy metals and organic compounds as well. However, other types of zeolites (e.g., phillipsite, chabazite) and clay minerals may dominate the mineral tuff assemblage, and properties of such materials may vary in the widest sense with respect to the final mineral content (Cejka, 2005). (2017). Cutovic M., Lazovic M., Vukovic-Dejanovic V., Nikolic D., Petronic-Markovic I., Cirovic D. (2017). Reactive oxygen species: role in the development of cancer and various chronic conditions. Even though the exact mechanisms remain elusive, one may speculate that clinoptilolite silica or released silica acts as a superantigen that promotes the formation of IgA producing plasma cells, which is dependent on the presence of superantigen-reactive T cells. In the paper by Kraljevi Paveli et al. Paveli K., Hadzija M., Bedrica L., Paveli J., Diki I., Kati M., et al. (2001b). Other studies on detoxification properties of clinoptilolite materials in vivo performed so far have mainly been done on animals and they provide strong evidence on alleviating effects during exposure to different toxicants upon clinoptilolite supplementation. This veterinary application showed that mineral levels in the blood were not affected by clinoptilolite supplementation which may be relevant for human applications as well. Kraljevi Paveli S., Micek V., Filoevi A., Gumbarevi D., urga P., Bulog A., et al. (2007). Due to a number of positive effects on health, including detoxification properties, the usage of clinoptilolite-based products in vivo has increased enormously. Removal of methelyne blue by natural and Ca and K-exchanged zeolite treated with hydrogen peroxide. (2008). Similarly, clinoptilolite supplementation of Enterex, approved by the Cuban Drug Quality Control Agency, showed to be highly efficient in ameliorating diarrhea symptoms in several clinical studies on humans with acute diarrhea of different etiologies. A critical reconsideration of biomedical and veterinary applications of natural zeolites. A well-known and complex relationship between exercise and oxidative stress depends on many diverse factors. Safety of the material was also proven by Ivkovic et al. The In addition, EDTA and clinoptilolite supplementation exerted a protective effect on the brain tissue of mice intoxicated with lead by inducing antioxidant mechanisms and greater activity levels of catalase, SOD, glutathione peroxidase, and glutathione (Basha et al., 2013). The superantigens generally encompass some bacterial exotoxins and viral products with a potent non-specific immuno-stimulatory effect on large T-cells fractions. Ghiara M. R., Petti C., Franco E., Lonis R., Luxoro S., Gnazzo L. (1999). The role of Na/K-ATPase signaling in oxidative stress related to obesity and cardiovascular disease. Paveli K., oli M., Suboti B. As a consequence of fluoride-intoxication, inhibition of antioxidant enzymes occurred in pups along with lipid peroxidation. These changes in the M-cells then affect the Peyers patches as well. (2001a). (1994). Documented properties and effects of clinoptilolite relevant for biomedical applications and effects in animals and humans. Silicic acid in drinking water prevents age-related alterations in the endothelium-dependent vascular relaxation modulating eNOS and AQP1 expression in experimental mice: an immunohistochemical study. (1990), or as Co2+> Cu2+> Zn2+> Mn2+ by Erdem et al. Adsorption of divalent lead Ions by zeolites and activated carbon: effects of pH, temperature, and ionic strength. The authors show changes on the clinoptilolite surface upon activation that resulted in an improved Ni-ions absorption. Dimowa L. T., Petrov S. L., Shivachev B. L. (2013). Furthermore, interesting effects of clinoptilolite supplementation were documented in animals as well. Still, this effect should be evaluated along with factors such as, for example, the applied daily dosage, health status, or lifestyle. The Al3+ in most situations seeks out complexing agents with oxygen-atom donor sites, such as carboxylate or phosphate groups, e.g., from food in the intestine. (2001). Effects of long-term dietary supplementation with clinoptilolite on incidence of parturient paresis and serum concentrations of total calcium, phosphate, magnesium, potassium, and sodium in dairy cows. J1-8155, and the awards to establish the Farr Institute of Health Informatics Research, London, from the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institute for Social Care and Health Research, and Wellcome Trust (Grant No. Another clinical study on human subjects showed detoxifying effectiveness of clinoptilolite. Hayyan M., Hashim M. A., AlNashef I. M. (2016). The majority of natural zeolites are of volcanic origin and have a general formula, M2/n:Al2O3:xSiO2:yH2O, where M stands for the extra-framework cation (Bogdanov et al., 2009). Occurrence of clinoptilolite and modernite in tertiary calc-alkaline pyroclastites from Sardinia (Italy). In these cows, dietary administration of clinoptilolite alleviated the nitrate burden to the body and reduced the negative systemic effects of nitrates (Katsoulos et al., 2015). Question marks (?) The .gov means its official. Oral consumption of this type of zeolite, due to its extreme chemical stability, in EFSAs opinion, does not represent a potential risk for in vivo applications (EFSA Panel on Additives and Products or Substances used in Animal Feed, 2013). Katsoulos P. D., Karatzia M. A., Polizopoulou Z., Florou-Paneri P., Karatzias H. (2015). A study by Katsoulos et al. Modulation of the bifidobacterial communities of the dog microbiota by zeolite. (2005). Krewski D., Yokel R. A., Nieboer E., Borchelt D., Cohen J., Harry J., et al. The clinoptilolite structure is still not destroyed after 12 h of heating at 750C, whereas the heulandite structure is destroyed after 12 h at 450C (Ghiara et al., 1999). Therefore, the up and down test on mice was performed with doses ranging from 60 to 400 mg/mice/day. Indeed, different studies have shown that clinoptilolite materials provide direct detoxifying performance in vivo. This effect may probably be attributed to a direct adhesion of the viral particles on clinoptilolite in vitro, which then inhibits viral entrance in the cells and viral replication. These local effects may have a systemic echo on the whole immune status as well, as observed in some studies. What is the mechanism of formation of hydroxyaluminosilicates? The latter are rich in T cells, macrophages, and clinoptilolite- activated IgA secreting B and plasma cells. For instance, gastric acid in the stomach contains HCl at 0.050.1 M. In such an environment, a certain release of Al species from the clinoptilolite surface may well be hypothesized even though aluminum from the clinoptilolite materials does not enter the blood or accumulate in the body as shown in athletes supplemented with zeolite-clinoptilolite supplement (Lamprecht et al., 2015) or healthy rats supplemented with different clinoptilolite materials (Kraljevi Paveli et al., 2017) where aluminum released into systemic circulation was observed only in rats supplemented with synthetic zeolite A. Therefore, we propose that this clinoptilolite-induced M-cells communication with Peyers patches, as similarly shown by Pavelic et al. 1Department of Biotechnology, Centre for High-Throughput Technologies, University of Rijeka, Rijeka, Croatia, 3Computer Science Department, University College London, London, United Kingdom, 4Juraj Dobrila University of Pula, Pula, Croatia. IgA Response to symbiotic bacteria as a mediator of gut homeostasis. (2015). Indeed, the microbiota-clinoptilolite interaction may also underlie the observed immunomodulatory mechanism as well. Before (2015). Novel, oxygenated clinoptilolite material efficiently removes aluminium from aluminium chloride-intoxicated rats in vivo. Beltcheva M., Metcheva R., Topashka-Ancheva M., Popov N., Teodorova S., Heredia-Rojas J. Leaching of lead from clinoptilolite at acidic conditions. Petrakakis Y., Mylona E., Georgantas D., Grigoropoluou H. (2007). The mineral assemblies of the most common zeolite occurrences in nature are clinoptilolite- and mordenite-containing tuffs, in which the zeolite clinoptilolite and mordenite content is high (80% and over). We present a comprehensive review of clinoptilolite applications in veterinary and human medicine. To our knowledge, no negative effects on immune cells or tissue were documented in the scientific literature so far. Zeolites possess unique and outstanding physical and chemical properties. It can generally be stated that clinoptilolite loaded with potential toxicants in the intestine is then excreted along with toxicants (EFSA Panel on Additives and Products or Substances used in Animal Feed, 2013). Bethesda, MD 20894, Web Policies In addition, earlier in Pond and Yen (1983) published the first study on the clinoptilolite effects on the reproduction and progeny growth in rats with or without cadmium presence. For example, selectivity alignments of the zeolite clinoptilolite cation exchange have been given as Ba2+> Cu2+, Zn2+> Cd2+, Sr2+> Co2+ by Blanchard et al. will also be available for a limited time. Recently, a preliminary efficacy study performed on patients with dyslipidemia has also shown a positive effect of clinoptilolite supplementation on lowering the total lipid count and LDL (low density lipoproteins), which may also be indirectly correlated with its general antioxidative effect (Cutovic et al., 2017). Even though the inspection of limited histopathological sections in this study cannot rule out the suggested hypothesis on clinoptilolite particles or silica particles released from clinoptilolite material (tuff) in activation of Peyer patches, experimental analysis of the observed local immunomodulatory effect should be conducted in more detail. Chen X., Song M., Zhang B., Zhang Y. Similarly, in the study by Fokas et al. These subjects also have increased intestinal wall permeability. La roca magica: uses of natural zeolites in agriculture and industry. Anticancer and antioxidative effects of micronized zeolite clinoptilolite. (2016). Blanchard G., Maunaye M., Martin G. (1984). Sorption hysteresis of Cd(II) and Pb(II) on natural zeolite and bentonite. Even though the efficacy and potential of clinoptilolite materials in medicine seems high, questions have been raised on to possible clinoptilolite effects on physiologically relevant elements, i.e., micronutrients and trace elements, or effects on important processes in the organism. For example, a proper mining process with adequate cleaning, sieving, de-hydrating, and pre-milling processes, along with elemental and microbiological examination of the clinoptilolite materials, might be considered among essential requirements for ensuring purity and quality (in relation to the high clinoptilolite content in the tuff) of the final materials for in vivo consumption. The authors conducted the study according to the standard procedures, Toxicity Characteristic Leaching Procedure/Environmental protection agency/Resource Conservation and Recovery Act (TCLP/EPA/RCRA) (1311), EPA Methods 1310, 1320 and DIN 38414-S4, and provided evidence of the pH being the main factor affecting Pb leaching from clinoptilolite. Activation may be performed either through chemical treatment, e.g., with an acid, by replacing stabilizing cations, or through mechanical modifications by means of different micronization methods, which may all increase the surface area and change the ion-exchange properties and adsorption capacity (Abdulkerim, 2012; Akimkhan, 2012; Canli et al., 2013b). (2016). For example, the kaolinite structure may change during the ion-exchange processes due to the displacement of H+ ions or due to the swelling of the structure as a consequence of Pb, Zn, or Cd cations absorption, which is opposite to the clinoptilolite constancy during ion-exchange process (Miranda-Trevino and Coles, 2003). Effect of in-feed inclusion of a natural zeolite (clinoptilolite) on certain vitamin, macro and trace element concentrations in the blood, liver and kidney tissues of sows. Learn more The high lead leakage from the material into the body is theoretically possible but this would eventually happen from tuff materials with extremely high content of lead where the theoretical absorption would be subject to many different physiological parameters and health conditions. Potentiated clinoptilolite: artificially enhanced aluminosilicate reduces symptoms associated with endoscopically negative gastroesophageal reflux disease and nonsteroidal anti-inflammatory drug induced gastritis. and transmitted securely. In the gastric juice, fluoride anions are converted into hydrofluoride acid. Moreover, a study in humans showed the ability of tribomechanically micronized clinoptilolite to decrease the absorption of ingested ethanol by reducing blood alcohol levels at a dose of 5 g (Federico et al., 2015). When ROS production exceeds antioxidant capacity, we usually perceive the process as oxidative stress that leads to organic damage. (2004), a significant increase in specific immunity cell counts, B lymphocite CD19+, T-helper cells CD4+, and activated T-lymphocytes HLA-DR+ were observed in subjects treated with tribomechanically micronized clinoptilolite. Effects of long-term feeding dairy cows on a diet supplemented with clinoptilolite on certain serum trace elements. In a study performed by Ivkovic et al. (2012). Beardmore J., Lopez X., Mujika J. I., Exley C. (2016). Some concerns were raised in public on the possible lead leakage from the natural clinoptilolite materials into the intestine. This is a well-known process in industrial applications, while for the in vivo applications it may also hold certain relevance. Enterex: anti-diarrheic drug based on purified natural clinoptilolite. Katsoulos P. D., Roubies N., Panousis N., Karatzias H. (2005b). The second option is through adsorption by forming a dipoldipol interaction between the polar channel and/or the zeolite surface and fluorine, or on the acid. sharing sensitive information, make sure youre on a federal The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile. For instance, it is well-known that tumor cells have increased hydrogen peroxide levels that regulate specific signaling pathways and hydrogen peroxide may modify cysteine residues on antioxidative enzymes (Lennicke et al., 2015). They are interconnected with ROS and activity of Nrf2 (Paveli et al., 2001b; Katic et al., 2006). Again, standard blood count parameters of patients remained within normal referent values (Ivkovic et al., 2004). A., et al. Miranda-Trevino J. C., Coles C. A. Mojzis J., Nistiar F., Kovac G., Mojzisova G. (1994). (2003). (2002), increases the immune response either through particle intake or microbiota effect as recently shown in dogs supplemented with the zeolite chabazite (Sabbioni et al., 2016), and in particular, stimulates IgA producing B lymphocytes (plasma cells), a defensive mechanism of the intestinal tract against pathogenic bacteria (Round and Mazmanian, 2009). Sung H. K., Jeung W., Choi I. D., Jeong J. W., Lee D. E., Huh C. S., et al. DG performed the literature search, participated in writing of the manuscript related to oxidative stress and immune system, and participated in shaping of the hypothesis of zeolite molecular effects in vivo. These cavities contain metal cations, which are exchangeable, or they may also host neutral guest molecules that can also be removed and replaced. A detailed explanation of the clinoptilolite structure is given in the Database of Zeolite Structures (http://europe.iza-structure.org/IZA-SC/ftc_table.php). No use, distribution or reproduction is permitted which does not comply with these terms. SKP generated the main idea and wrote the manuscript, generated and shaped presented hypotheses, performed literature search and analysis, prepared the figures and tables, discussed and systematized all literature data. et al., 2013). Toxicological evaluation of clay minerals and derived nanocomposites: a review. The name zeolite originates from the Greek words zeo(to boil) and litos (a stone). This will fill in the current gaps in research presented so far as similarly suggested by Colella (2011). A controlled production of ROS is indeed essential to the bodys homeostasis (Covarrubias, 2008), while an excessive production of ROS is known to cause damage to the DNA, proteins, and lipids (Gulam and Ahsan, 2006). Fluoride induced neuronal oxidative stress and its amelioration by antioxidants in developing rats. Emmer A., Staege M. S., Kornhuber M. E. (2014). Removal of ammonia ions and uremic toxins (urea, uric acid, creatinine, serotonergic 5-hydroxytryptamine receptors in the brain, 3[H]8-hydroxy-2-(di-n-propylamino)tetralin, Organization for Economic Cooperation and Development, Toxicity Characteristic Leaching Procedure/Environmental protection agency/Resource Conservation and Recovery Act. (2010). Therefore, this observed antidiarrheal activity may be in correlation with Enterex effect on certain pathogenic bacteria count or the microbiota status in general rather than with a direct antibacterial effect, which would have to be confirmed by additional studies. The superantigen-activated T-lymphocytes provoke the cellular immune response and also the humoral immune response, as postulated by Emmer et al. In that study, the effects associated with increasing exposure times were analyzed in three categories: (1) acute toxic responses up to 1 month in mice and rats, (2) subchronic toxic responses up to 3 months in mice and rats, and (3) chronic toxic responses up to 1 year in rats and 6 months in mice. However, conclusive statements on the exact applications and benefits of clinoptilolite-based materials in humans should be carefully investigated and analyzed for each specific clinoptilolite material as the mechanisms of action may have correlations with the specific materials physical and chemical properties. The effect of the zeolite clinoptilolite on serum chemistry and hematopoiesis in mice. Moreover, hydrochloric acid (HCl) that is also present in the stomach may change clinoptilolite physical chemical properties and has been proven to enhance the clinoptilolite ion-exchange capacity for Cu2+ and Co2+ in a synthetic Cu-Co solution at concentrations relevant for the stomach in vivo (0.1 M) (MambaI et al., 2010). M-cells are found in the GALT of Peyers patches, a rich lymphoid tissue that communicates with intestinal epithelial cells and the microbiome of the intestine by diverse immunomodulation processes as well as in the MALT of other parts of the gastrointestinal tract. Tomasevic-Canovic M., Dumic M., Vukicevic O., Duricic M., Jovanovic S. (1996). The excessive production of ammonia, but also of other gaseous products, including CO2 and H2S, may occur as a consequence of protein-rich or imbalanced diets, or in diverse pathogeneses where excessive protein fermentation occurs, including irritable bowel syndrome, ulcerative colitis, and colorectal carcinogenesis (Hughes and Magee, 2000; Yao et al., 2016). Montinaro M., Uberti D., Maccarinelli G., Bonini S. A., Ferrari-Toninelli G., Memo M. (2013). Martin-Kleiner I., Flegar-Metri Z., Zadro R., Breljak D., Stanovi Janda S., Stojkovi R., et al. (2016). The depletion of hydrogen peroxide and the increased ROS production during hydrogen peroxide reaction with a clinoptilolite surface may change the redox status of the cell, e.g., through inhibition of the transcription factor Nrf2. Finally, clinoptilolites antioxidant effects and restoration of antioxidant defense mechanisms may also be linked to the positive general systemic impact. Some ROS are produced endogenously, while others are derived exogenously, such as those formed by ionizing radiation. Contrary to M-cells, other cells in the intestine cannot perform macropinocytosis and therefore cannot absorb negatively charged clinoptilolite particles or silica particles released from the clinoptilolite material (tuff) due to their rich negatively-charged glycoprotein-polysaccharide covering, glycocalix (Egberts et al., 1984). Studies on free radicals, antioxidants, and co-factors. During treatment with activated clinoptilolite from 7 to 30 days in total, both urine and blood serum were collected and tested for heavy metals and electrolytes. For instance, regular moderate exercise increases the resistance against oxidative stress, while acute and vigorous exercise can generate free radicals in excess. Due to clinoptilolites remarkable ion-exchange and adsorption properties and consequent detoxifying effects, it has proven useful in the elimination of a variety of contaminants from the body or in amelioration of the intestinal status. Beltcheva M., Metcheva R., Popov N., Teodorova S. E., Heredia-Rojas J. Characterization of kaolin dispersion using acoustic and electroacoustic spectroscopy. The latter effect was attributed to the zeolite A lower stability in the acidic pH relevant for the human intestine in comparison to clinoptilolite materials. (2014) So far the word zeolite has been used in the literature for different types of zeolites, tuffs, and clays. (2001b). Sabbioni A., Ferrario C., Milani C., Mancabelli L., Riccardi E., Di Ianni F., et al. Careers, Edited by: Lei Xi, Virginia Commonwealth University, United States, Reviewed by: Panagiotis Dimitrios Katsoulos, Aristotle University of Thessaloniki, Greece; Stephane Nizet, GLOCK Health, Science and Research G.m.b.H., Austria. The current nomenclature and classification of zeolite materials has been provided by the Structure Commission of the International Zeolite Association that identifies each material based on their framework with a three-letter mnemonic code; for instance, natural zeolite clinoptilolite is denoted as HEU (Baerlocher et al., 2007). (2007). Fokas P., Zervas G., Fegeros K., Zoiopoulos P. (2004). The endogenous sources of ROS are the mitochondria, cytochrome P450 metabolism, peroxisomes, and inflammatory cell activation (Inoue et al., 2003). (2016). While the total count of E. coli was significantly reduced, a rise of Lactobacillus acidophilus occurred in parallel (Zarkovic et al., 2003). Darwin, natural selection and the biological essentiality of aluminium and silicon. Enzyme systems rely mainly on SOD, catalase, peroxiredoxin (Prx), thioredoxins (Trx), and glutathione (GSH) enzymes activity, while non-enzymatic systems comprise flavonoids, vitamin A, vitamin C, vitamin E, and melatonin (Rahman, 2007). Also, Muck-Seler and Pivac (2003) studied the effects of tribomechanically micronized and non-micronized clinoptilolite materials on the serotonergic 5-hydroxytryptamine receptors 5-HT(1A) and 5-HT(1B) in the brain of non-tumorous (control) and mammary carcinoma-bearing female mice. In a recent article, Turkish clinoptilolite was activated with hydrogen peroxide, which acts as a weak acid, to improve Ni2+ ions removal from aqueous solutions (anli and Abali, 2016). An official website of the United States government. Tumor cells are susceptible to increased oxidative stress and in our previous experiments, this effect was not visible or was lower in normal tested fibroblasts in vitro (Katic et al., 2006). A total of 102 heavy-metal contaminated men were investigated and decreased concentrations of harmful metals (Cd, Pb, Cu, Cr, and Ni) were measured in their hair after a 30-day supplementation with clinoptilolite. Similarly, in another study performed by the European Union Cosmetic Ingredient Review Expert Panel, natural clinoptilolite showed no effects on female rat reproductive performance and it proved non-genotoxic in the Ames bacterial test system (Elmore, 2003). A reduced binding of 3[H]8-hydroxy-2-(di-n-propylamino)tetralin (3H-8-OH-DPAT) to 5-HT(1A) receptors in mammary carcinoma-bearing mice was normalized in animals supplemented by tribomechanically-micronized clinoptilolite. Such a wide use of antibiotics in poultry, but also in the production of other meat, has recently been accepted as a major cause for development of antibiotic-resistant bacteria (Aminov and Mackie, 2007). The mineral structure is based on AlO4 and SiO4 tetrahedra, which can share 1, 2, or 3 oxygen atoms, so there is a wide variety of possible structures as the network is extended in three dimensions. Indeed, ROS induces cell and tissue damage when the inflammation is initiated as a mechanism for restoration of the bodys homeostasis. Indeed, previous studies have shown a link between the antioxidative effect and the stimulation of the immune system (Knight, 2000; Brambilla et al., 2008). New, natural possibilities for improvement of animal health in meat production have therefore been widely discussed (Diaz-Sanchez et al., 2015) and clinoptilolite may be a natural alternative. The single layer of the intestinal epithelium is protected by mucus containing mucin glycoproteins where immunoglobulin A (IgA) and antimicrobial peptides prevent interaction of microbiota with the cell surface. Katsoulos P. D., Zarogiannis S., Roubies N., Christodoulopoulos G. (2009). In vivo, the acid concentrations of the intestine are substantially lower than those used in industrial activation process. NP performed a critical review of data and literature, edited the paper content and its final content. in: biocatalysis and biomimetics. Ryoo I. G., Lee S. H., Kwak M. K. (2016). As a consequence, de-alumination of the surface occurs, which increases the Si/Al surface ratio and absorption capacity for metal cations. Accessibility While evaluating possible clinoptilolite immunomodulatory effects in the intestine, it should be emphasized that M-cells can uptake nano- and submicro-particles, which can probably induce changes in the redox homeostasis in a cell (Igarashi, 2015). Besides metal cations and water resident in zeolites cavities and pores, other molecules and cationic groups may be accommodated as well, such as, for instance, ammonia, and nitrate ions, all of which are bound to different zeolites at different affinity levels (Gaikwad and Warade, 2014). It may appear with the aluminum phyllosilicate clay smectite (bentonite) and accompanying phases present in lower percentages cristoballite, calcite, feldspar, and quartz. We greatly acknowledge the support of the University of Rijeka (Grant Nos. Biological and pathobiological aspects of the glycocalyx of the small intestinal epithelium. Natural zeolite clinoptilolite: new adjuvant in anticancer therapy. 8600 Rockville Pike Zeolite clinoptilolite nanoporous feed additive for animals of veterinary importance: potentials and limitations, Protective effects of zinc-bearing clinoptilolite on broilers challenged with. Kaolinite properties, structure and influence of metal retention on pH. Prasai T. P., Walsh K. B., Bhattarai S. P., Midmore D. J., Van T. T. H., Moore R. J., et al. Similarly, in doxorubicin treated mice, micronized clinoptilolite proved efficient in counteracting lipid peroxidation in the liver (Zarkovic et al., 2003). Inoue M., Sato E. F., Nishikawa M., Park A. M., Kira Y., Imada I., et al. This is important, as hydrogen peroxide dissociates into hydrogen ion H+ and hydrogen peroxide radical (HO2), and during the acid-activation process H+ ions are brought to the negatively-charged species on the material surface. Proposed model of clinoptilolite positive immunomodulatory effect in the intestinal epithelium (denoted with red arrows) through interaction of clinoptilolite tuff particles with microfold cells (M-cells). It is plausible, therefore, to assume that such disorders have the formation of biofilms in common due to the impaired immunological reaction of the host organism (Pincus, 2005). Cosmetic ingredient review expert panel final Report on the safety assessment of aluminum silicate, calcium silicate, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, sodium magnesium silicate, zirconium silicate, attapulgite, bentonite, Fullers Earth, hectorite, kaolin, lithium magnesium silicate, lithium magnesium sodium silicate, montmorillonite, pyrophyllite, and zeolite. No effects of clinoptilolite on physiological mineral levels have been observed in cows (Katsoulos et al., 2005a; Valpoti et al., 2017).
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