The .gov means its official. For example, detrimental roles of the end-products of protein fermentation, such as ammonia, have been recognized on the colonic microbiota and epithelial health, in particular on the colonocytes life span and function (Hughes and Magee, 2000; Yao et al., 2016; Hamid Said, 2018). 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). A pilot study on the ability of clinoptilolite to absorb ethanol in vivo in healthy drinkers: effect of gender. 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). Indeed, ROS induces cell and tissue damage when the inflammation is initiated as a mechanism for restoration of the bodys homeostasis. Ammonium sorption from aqueous solutions by the natural zeolite transcarpathian clinoptilolite studied under dynamic conditions. A clinoptilolite effect on cell media and the consequent effects on tumor cells in vitro. (2014) So far the word zeolite has been used in the literature for different types of zeolites, tuffs, and clays. Review: free radicals, antioxidants, and the immune system. 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). Katsoulos P. D., Roubies N., Panousis N., Arsenos G., Christaki E., Karatzias H. (2005a). (1998). Sabbioni A., Ferrario C., Milani C., Mancabelli L., Riccardi E., Di Ianni F., et al. Selvam T., Schwieger W., Dathe W. (2014). 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). Chen X., Song M., Zhang B., Zhang Y. (2016). A study by Katsoulos et al. However, concerns have been raised in the public about the safety of clinoptilolite materials for in vivo applications. and transmitted securely. 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. 
Two possible ways of binding organophosphates may be envisaged. 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. Documented properties and effects of clinoptilolite relevant for biomedical applications and effects in animals and humans. Impact of medicated feed along with clay mineral supplementation on, Application of zeolite in biomedical engineering: a review, in. (1994). Valpoti H., Graer D., Turk R., urii D., Vince S., Folnoi I., et al. Oxidative stress in diabetic nephropathy with early chronic kidney disease. For example, dietary compounds are highly important for elimination of excessive ROS caused by external stimuli and include, for instance, carotenoids, tocopherols, bioflavonoids, anthocyanins, and phenolic acid (Smilin Bell Aseervatham et al., 2013). This is why antibiotics are standardly used in poultry meat production. Bingham S., colonic protein metabolism and colorectal cancer. The authors show changes on the clinoptilolite surface upon activation that resulted in an improved Ni-ions absorption. (2017), it was specifically shown that different micronization methods change the clinoptilolite tuff properties by affecting the surface area, pore size, and silicon to aluminum ratio on the surface of the material.
We consider all of the above clinoptilolite properties and propose its mechanisms of action in vivo (summarized in Table Table1)1) and propose some comprehensive, scientifically-based hypotheses on possible biological mechanisms underlying observed effects on the health and body homeostasis. For instance, in long-term supplementation with clinoptilolite, a decreased prevalence of E. coli carrying certain antimicrobial resistance and virulence genes was documented (Jahanbakhsh et al., 2015). Madhusudhan N., Basha P. M., Begum S., Ahmed F. (2009). Recalculated from human use, they were 10 and 25 times higher than envisaged potential human exposure dosages (60 g/75 kg human body weight and 150 g/75 kg human body weight). The structure of mineral clays is, for instance, organized in layers (sheets), while clinoptilolite has tetrahedra arranged in a way that they form large amounts of pore space in the crystals. Adsorption of water by clinoptilolite and glauconite. Some probiotics metabolites, e.g., from the lactic acid bacteria, exert the same activating function on Peyers patches as we suggest for clinoptilolite particles or silica particles released from the clinoptilolite material (tuff) and improve intestinal wall integrity (Sung et al., 2016). The The basic structure of clinoptilolite is considered to be biologically neutral and non-toxic (Auerbach et al., 2003). (1997).
Zeolite clinoptilolite nanoporous feed additive for animals of veterinary importance: potentials and limitations, Protective effects of zinc-bearing clinoptilolite on broilers challenged with. about navigating our updated article layout. Bogdanov B., Georgiev D., Angelova K., Yaneva K. (2009). Ryoo I. G., Lee S. H., Kwak M. K. (2016). Darwin, natural selection and the biological essentiality of aluminium and silicon. 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. Activation-induced cell death in human peripheral blood lymphocytes after stimulation with silicate in vitro. Natural zeolite clinoptilolite: new adjuvant in anticancer therapy. In this preclinical toxicology study, tribomechanically micronized clinoptilolite was evaluated at the Ruer Bokovi Institute in Zagreb, Croatia, according to the standards and regulations required at the time by the OECD. For instance, tribomechanically-micronized zeolite increased SOD activity in a transgenic mouse model of the Alzheimer disease in the hippocampus and cortex, while it concomitantly reduced A (x-42) amyloid beta levels in the hippocampus (Montinaro et al., 2013). Lennicke C., Rahn J., Lichtenfels R. A., Wessjohann L. A., Seliger B. When ROS production exceeds antioxidant capacity, we usually perceive the process as oxidative stress that leads to organic damage. 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). Urine is, indeed, important in elimination of lead released from the bones or body compartments, i.e., in chelation therapy where upon quenching of lead from different sites of the body it is expelled through urine (Flora et al., 2012). AF performed literature search on physical-chemical properties of clinoptilolite and wrote parts of the manuscript related to clinoptilolite chemistry. Dimowa L. T., Petrov S. L., Shivachev B. L. (2013). Potential role of infections in chronic inflammatory diseases. 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). Federal government websites often end in .gov or .mil. We hypothesize that they may be at least partially attributed to the restoration of the human homeostasis due to local detoxification properties within the intestine, the release of dissolved silica forms from the clinoptilolite tuff that enter from the intestine into the blood, as well as to clinoptilolites immunomodulatory effects. Superoxide ion: generation and chemical Implications. Similar results were, however, observed in animals supplemented with vitamins E and C as well (Madhusudhan et al., 2009). 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. Upon supplementation of pups with clinoptilolite, oxidative damage was restored and levels of GSH-Prx were substantially ameliorated in the cerebral cortex and medulla oblongata. Clinoptilolite shares a high structural similarity with the zeolite heulandite (they are isostructural) and it is distinguished from helaundite by a higher silicon to aluminum ratio in favor to silicon, where Si / Al > 4.0 and (Na + K) > (Ca + Sr + Ba).
(2015). 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. In this study, the daily intake of activated clinoptilolite suspension was effective in removal of toxic heavy metals from the body via urine (Flowers et al., 2009). Human health risk assesement for aluminum, aluminium oxide, and aluminium hydroxyde. Aikoh T., Tomokuni A., Matsukii T., Hyodoh F., Ueki H., Otsuki T., et al. Effect of long-term dietary supplementation with clinoptilolite on performance and selected serum biochemical values in dairy goats. Some of the alkaline ions contained in the crystal lattice, mainly Na+, Ca2+, Mg2, and K+, may be readily released during the ion-exchange process. This structural stability is an essential element for in vivo applications. (2001b). In agreement with the scientific evidence presented in the literature so far, it can be generally stated that clinoptilolite-based materials, including the so-called activated materials, may be regarded as safe for in vivo consumption. Brambilla D., Mancuso C., Scuderi M. R., Bosco P., Cantarella G., Lempereur L., et al. Importantly, while great danger exists in removing the physiologically important electrolytes from the serum in a classical detoxification process, this has not been observed in clinoptilolite trials both in humans and animals, where no substantial changes in physiologically relevant trace elements or vitamins were observed even after long-term administration (Papaioannou et al., 2002; Katsoulos et al., 2005b; Flowers et al., 2009). http://www.chemtube3d.com/solidstate/SS-Z-Clinoptilolite.htm, http://europe.iza-structure.org/IZA-SC/ftc_table.php, EFSA Panel on Additives and Products or Substances used in Animal Feed, 2013, Morillas-Ruiz and Hernndez-Snchez, 2015, Molecular sieve (size and shape selectivity) (. zeolite, clinoptilolite, toxicology, immunostimulation, antioxidant properties. (2007). Speciation of aluminum in biological systems. Polyclonal human T-cell activation by silicate in vitro. Modulation of the bifidobacterial communities of the dog microbiota by zeolite. The site is secure. Influence of acid activation on the ion-exchange properties of manisa-gordes clinoptilolite. Function of reactive oxygen species during animal development: passive or active? Collela also emphasized the variability and heterogeneity of the clinoptilolite material used in different applications and studies and suggested to study in detail the applications and mechanisms of clinoptilolite materials in light of known and well-established properties or behaviors. The role of clinoptilolite has been recognized in medical applications, where its usage in zootechnology and veterinary medicine has provided strong evidence on improvement of pets fitness and efficiency in the removal of numerous harmful substances from the organism, including radioactive elements, mycotoxins, and poisons (Laurino and Palmieri, 2015). Even though in the majority of in vitro studies, the cells were grown in micronized clinoptilolite pre-treated growth media, no ultracentrifugation was employed, which means that a colloid system containing finest clinoptilolite particles was used for experiments (Paveli et al., 2001b; Katic et al., 2006). Hydrogen peroxide production, fate and role in redox signaling of tumor cells. While the total count of E. coli was significantly reduced, a rise of Lactobacillus acidophilus occurred in parallel (Zarkovic et al., 2003). The Pb leaching percentage may, in the authors opinion, be generally correlated with an increasing initial load but is not affected by the agitation rate or particle size. Nizet S., Muoz E., Fiebich B. L., Abuja P. M., Kashofer K., Katloukal K., et al. Two doses were selected from the limit test, 400 mg/mice/day (3.2 times higher than the dose specified by the regulatory agency) and 1000 mg/mice/day (8 times higher). (2009). 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. Federico A., Dallio M., Gravina A. G., Iannotta C., Romano M., Rossetti G., et al. 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. FOIA Nano- and microsized zeolites as a perspective material for potentiometric biosensors creation. In line with these results, it should also be hypothesized that clinoptilolite might have the potential to combat acute fluoride-intoxication in animals, as well as in humans.
Two possible ways of binding organophosphates may be envisaged. 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. Documented properties and effects of clinoptilolite relevant for biomedical applications and effects in animals and humans. Impact of medicated feed along with clay mineral supplementation on, Application of zeolite in biomedical engineering: a review, in. (1994). Valpoti H., Graer D., Turk R., urii D., Vince S., Folnoi I., et al. Oxidative stress in diabetic nephropathy with early chronic kidney disease. For example, dietary compounds are highly important for elimination of excessive ROS caused by external stimuli and include, for instance, carotenoids, tocopherols, bioflavonoids, anthocyanins, and phenolic acid (Smilin Bell Aseervatham et al., 2013). This is why antibiotics are standardly used in poultry meat production. Bingham S., colonic protein metabolism and colorectal cancer. The authors show changes on the clinoptilolite surface upon activation that resulted in an improved Ni-ions absorption. (2017), it was specifically shown that different micronization methods change the clinoptilolite tuff properties by affecting the surface area, pore size, and silicon to aluminum ratio on the surface of the material. We consider all of the above clinoptilolite properties and propose its mechanisms of action in vivo (summarized in Table Table1)1) and propose some comprehensive, scientifically-based hypotheses on possible biological mechanisms underlying observed effects on the health and body homeostasis. For instance, in long-term supplementation with clinoptilolite, a decreased prevalence of E. coli carrying certain antimicrobial resistance and virulence genes was documented (Jahanbakhsh et al., 2015). Madhusudhan N., Basha P. M., Begum S., Ahmed F. (2009). Recalculated from human use, they were 10 and 25 times higher than envisaged potential human exposure dosages (60 g/75 kg human body weight and 150 g/75 kg human body weight). The structure of mineral clays is, for instance, organized in layers (sheets), while clinoptilolite has tetrahedra arranged in a way that they form large amounts of pore space in the crystals. Adsorption of water by clinoptilolite and glauconite. Some probiotics metabolites, e.g., from the lactic acid bacteria, exert the same activating function on Peyers patches as we suggest for clinoptilolite particles or silica particles released from the clinoptilolite material (tuff) and improve intestinal wall integrity (Sung et al., 2016). The The basic structure of clinoptilolite is considered to be biologically neutral and non-toxic (Auerbach et al., 2003). (1997).
Zeolite clinoptilolite nanoporous feed additive for animals of veterinary importance: potentials and limitations, Protective effects of zinc-bearing clinoptilolite on broilers challenged with. about navigating our updated article layout. Bogdanov B., Georgiev D., Angelova K., Yaneva K. (2009). Ryoo I. G., Lee S. H., Kwak M. K. (2016). Darwin, natural selection and the biological essentiality of aluminium and silicon. 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. Activation-induced cell death in human peripheral blood lymphocytes after stimulation with silicate in vitro. Natural zeolite clinoptilolite: new adjuvant in anticancer therapy. In this preclinical toxicology study, tribomechanically micronized clinoptilolite was evaluated at the Ruer Bokovi Institute in Zagreb, Croatia, according to the standards and regulations required at the time by the OECD. For instance, tribomechanically-micronized zeolite increased SOD activity in a transgenic mouse model of the Alzheimer disease in the hippocampus and cortex, while it concomitantly reduced A (x-42) amyloid beta levels in the hippocampus (Montinaro et al., 2013). Lennicke C., Rahn J., Lichtenfels R. A., Wessjohann L. A., Seliger B. When ROS production exceeds antioxidant capacity, we usually perceive the process as oxidative stress that leads to organic damage. 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). Urine is, indeed, important in elimination of lead released from the bones or body compartments, i.e., in chelation therapy where upon quenching of lead from different sites of the body it is expelled through urine (Flora et al., 2012). AF performed literature search on physical-chemical properties of clinoptilolite and wrote parts of the manuscript related to clinoptilolite chemistry. Dimowa L. T., Petrov S. L., Shivachev B. L. (2013). Potential role of infections in chronic inflammatory diseases. 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). Federal government websites often end in .gov or .mil. We hypothesize that they may be at least partially attributed to the restoration of the human homeostasis due to local detoxification properties within the intestine, the release of dissolved silica forms from the clinoptilolite tuff that enter from the intestine into the blood, as well as to clinoptilolites immunomodulatory effects. Superoxide ion: generation and chemical Implications. Similar results were, however, observed in animals supplemented with vitamins E and C as well (Madhusudhan et al., 2009). 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. Upon supplementation of pups with clinoptilolite, oxidative damage was restored and levels of GSH-Prx were substantially ameliorated in the cerebral cortex and medulla oblongata. Clinoptilolite shares a high structural similarity with the zeolite heulandite (they are isostructural) and it is distinguished from helaundite by a higher silicon to aluminum ratio in favor to silicon, where Si / Al > 4.0 and (Na + K) > (Ca + Sr + Ba).
(2015). 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. In this study, the daily intake of activated clinoptilolite suspension was effective in removal of toxic heavy metals from the body via urine (Flowers et al., 2009). Human health risk assesement for aluminum, aluminium oxide, and aluminium hydroxyde. Aikoh T., Tomokuni A., Matsukii T., Hyodoh F., Ueki H., Otsuki T., et al. Effect of long-term dietary supplementation with clinoptilolite on performance and selected serum biochemical values in dairy goats. Some of the alkaline ions contained in the crystal lattice, mainly Na+, Ca2+, Mg2, and K+, may be readily released during the ion-exchange process. This structural stability is an essential element for in vivo applications. (2001b). In agreement with the scientific evidence presented in the literature so far, it can be generally stated that clinoptilolite-based materials, including the so-called activated materials, may be regarded as safe for in vivo consumption. Brambilla D., Mancuso C., Scuderi M. R., Bosco P., Cantarella G., Lempereur L., et al. Importantly, while great danger exists in removing the physiologically important electrolytes from the serum in a classical detoxification process, this has not been observed in clinoptilolite trials both in humans and animals, where no substantial changes in physiologically relevant trace elements or vitamins were observed even after long-term administration (Papaioannou et al., 2002; Katsoulos et al., 2005b; Flowers et al., 2009). http://www.chemtube3d.com/solidstate/SS-Z-Clinoptilolite.htm, http://europe.iza-structure.org/IZA-SC/ftc_table.php, EFSA Panel on Additives and Products or Substances used in Animal Feed, 2013, Morillas-Ruiz and Hernndez-Snchez, 2015, Molecular sieve (size and shape selectivity) (. zeolite, clinoptilolite, toxicology, immunostimulation, antioxidant properties. (2007). Speciation of aluminum in biological systems. Polyclonal human T-cell activation by silicate in vitro. Modulation of the bifidobacterial communities of the dog microbiota by zeolite. The site is secure. Influence of acid activation on the ion-exchange properties of manisa-gordes clinoptilolite. Function of reactive oxygen species during animal development: passive or active? Collela also emphasized the variability and heterogeneity of the clinoptilolite material used in different applications and studies and suggested to study in detail the applications and mechanisms of clinoptilolite materials in light of known and well-established properties or behaviors. The role of clinoptilolite has been recognized in medical applications, where its usage in zootechnology and veterinary medicine has provided strong evidence on improvement of pets fitness and efficiency in the removal of numerous harmful substances from the organism, including radioactive elements, mycotoxins, and poisons (Laurino and Palmieri, 2015). Even though in the majority of in vitro studies, the cells were grown in micronized clinoptilolite pre-treated growth media, no ultracentrifugation was employed, which means that a colloid system containing finest clinoptilolite particles was used for experiments (Paveli et al., 2001b; Katic et al., 2006). Hydrogen peroxide production, fate and role in redox signaling of tumor cells. While the total count of E. coli was significantly reduced, a rise of Lactobacillus acidophilus occurred in parallel (Zarkovic et al., 2003). The Pb leaching percentage may, in the authors opinion, be generally correlated with an increasing initial load but is not affected by the agitation rate or particle size. Nizet S., Muoz E., Fiebich B. L., Abuja P. M., Kashofer K., Katloukal K., et al. Two doses were selected from the limit test, 400 mg/mice/day (3.2 times higher than the dose specified by the regulatory agency) and 1000 mg/mice/day (8 times higher). (2009). 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. Federico A., Dallio M., Gravina A. G., Iannotta C., Romano M., Rossetti G., et al. 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. FOIA Nano- and microsized zeolites as a perspective material for potentiometric biosensors creation. In line with these results, it should also be hypothesized that clinoptilolite might have the potential to combat acute fluoride-intoxication in animals, as well as in humans.