Environmental factors and unhealthy lifestyle influence oxidative stress in humansan overview. Its structure consists of an outer framework of silica and alumina tetrahedra, within which water molecules and exchangeable cations (e.g., calcium, potassium, sodium) migrate freely. Critical Review on Zeolite Clinoptilolite Safety and Medical Silicon-rich mineral water as a non-invasive test of the aluminum hypothesis in Alzheimers disease. A neuroprotective effect was also documented by Basha et al. 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. In case of antioxidant enzymes, these co-factors may include the coenzyme Q10, vitamins B1 and B2, carnitine, selenium, and often transition metals Cu, Mn, Fe, and Zn (Khalid, 2007). A large number of documented positive clinoptilolite medical effects were attributed to basic clinoptilolite material properties, in particular, to reversible ion-exchange and adsorption capacity (Mumpton, 1999; Paveli et al., 2001a; Jurki et al., 2013). Also, we cannot rule out some other unrecognized immunomodulatory effects of clinoptilolite due to a direct interaction with human microbiome (Figure (Figure33). We focus on the safety of the clinoptilolite material and the positive medical effects related to detoxification, immune response, and the general health status. Based on the pore size and absorption properties, zeolites are among the most important inorganic cation exchangers and are used in industrial applications for water and waste water treatment, catalysis, nuclear waste, agriculture, animal feed additives, and in biochemical applications (Bogdanov et al., 2009). Chen X., Song M., Zhang B., Zhang Y. KP performed literature search related to clinical aspects and toxicology, discussed clinical aspects, and helped to draft the manuscript. Immunostimulatory effect of natural clinoptilolite as a possible mechanism of its antimetastatic ability. Tomasevic-Canovic M., Dumic M., Vukicevic O., Duricic M., Jovanovic S. (1996). In contrast, zeolites with higher silica content, such as clinoptilolite, are stable in acids (Payra and Dutta, 2003). 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. Evolution and ecology of antibiotic resistance genes. Interestingly, the supplementation with Panaceo Sport positively influenced the intestinal wall integrity, which was witnessed through decreased concentrations of the tight junction modulator zonulin, a marker of increased intestinal permeability (Lamprecht et al., 2015). Studies on free radicals, antioxidants, and co-factors. If the clinoptilolite-containing product dosage is lower or if it is not administered at the time of alcohol consumption, this effect may not be visible as shown by Gandy et al. Clinoptilolite in dextran sulphate sodium-Induced murine colitis: efficacy and safety of a microparticulate preparation. (2016). For example, nontoxic natural zeolite clinoptilolite affects tumour cells proliferation in vitro and might act as an adjuvant in cancer therapy . [PDF] Natural zeolite clinoptilolite: new adjuvant in anticancer The isomerization of S-carvone was carried out at the catalyst content in the reaction mixture from 5 to 15 wt%, in a temperature range of 190-210 C and for the reaction time from 60 to 300 min. Anticancer and antioxidative effects of micronized zeolite clinoptilolite. It forms as white, green to reddish tabular monoclinic tectosilicate crystals with a Mohs hardness of 3.5 to 4 and a specific gravity of 2.1 to 2.2. Objectives: A tribomechanically activated clinoptilolite (natural aluminosilicate mineral) has been used to increase growth in meat-producing animals, as an adjuvant in cancer therapy, and a heavy metal remover in humans. 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. 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. Biological and therapeutic effects of ortho-silicic acid and some ortho Recently, a positive effect of a potentiated clinoptilolite material (Absorbatox) was also shown to reduce symptoms associated with endoscopically negative gastroesophageal reflux disease and non-steroidal anti-inflammatory drug-induced gastritis, where it significantly prevented mucosal erosion severity (Potgieter et al., 2014). In this report we studied the effect of Natural Clinoptilolite Zeoliteparticles on development of several cancer models in vivo and in vitro.We found that mechanically activated clinoptilolite zeolites act as anticancer therapeutic agents in in vivo animal studies and in tissue culture cell models. Pingitore A., Lima G. P., Mastorci F., Quinones A., Iervasi G., Vassalle C. (2015). However, it should be noted that the aqueous coordination chemistry of Al3+, especially in the living systems, is rather complex due to the Al-complexes tendency to hydrolyze and form polynuclear species, which vary according to the pH condition of the medium (Wesley, 1996; Krewski et al., 2009). 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). As a consequence, de-alumination of the surface occurs, which increases the Si/Al surface ratio and absorption capacity for metal cations. Clinoptilolite has a high affinity toward ammonium and may prove useful in these cases as an adjuvant to the standard therapy (Yao et al., 2016). These local effects may have a systemic echo on the whole immune status as well, as observed in some studies. (1998). Affinity toward aflatoxins, zearalenone, ochratoxin, and the T2 toxin was proven in vitro in the presence of aminoacids and vitamins, where the latter were not absorbed by the clinoptilolite material (Tomasevic-Canovic et al., 1996). IgA Response to symbiotic bacteria as a mediator of gut homeostasis. 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. (2017). Botanical alternatives to antibiotics for use in organic poultry production. Food Chem Toxicol. In aerobic organisms, production of small quantities of ROS, including peroxides, superoxides, hydroxyl radicals, and singlet oxygen, occurs continuously (Hayyan et al., 2016). It is important to note that the supplementation with clinoptilolite in dairy cows may have additional benefits, such as the reduction of parturient paresis. An incredibly heterogeneous T-cell clonal activation occurs upon binding and different cytokines are produced massively (Proft and Fraser, 2016). 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). Wu Q. J., Wang L. C., Zhou Y. M., Zhang J. F., Wang T. (2013). Wu Y., Wu Q., Zhou Y., Ahmad H., Wang T. (2013). Beltcheva M., Metcheva R., Topashka-Ancheva M., Popov N., Teodorova S., Heredia-Rojas J. The effect of the zeolite clinoptilolite on serum chemistry and hematopoiesis in mice. The gut microbiome shapes intestinal immune responses during health and disease. 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) (. 8600 Rockville Pike Zeolites cancer treatment, heavy metals / pesticide detoxifier We believe that exact mechanisms of clinoptilolite effects on systemic restoration of homeostasis and increased antioxidant capacity are still not fully understood, as these effects are in our opinion probably connected both to general detoxifying effects occurring in the intestine, to immunomodulatory effects, or even to the release of physiologically-relevant cations from the clinoptilolite framework during the ion exchange process, e.g., Ca, Mn, Zn, and Mg, which are then readily available to the organism and the antioxidant mechanism. 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. Hayakawa K., Mouri Y., Maeda T., Satake I., Sato M. (2000). Structural and ion-exchange properties of natural zeolite, in. Again, no toxicity was observed. Lamprecht M., Bogner S., Steinbauer K., Schuetz B., Geilberger J. F., Leber B., et al. Pavelic K, Katic M, Sverko V, et al. Superantigens bind to the variable V region of the T-cell receptor or to CD28 and do not follow the peptide-binding pattern. NP was funded by the European Research Council (ERC) Starting Independent Researcher Grant 278212, the European Research Council (ERC) Consolidator Grant No. This is a well-known process in industrial applications, while for the in vivo applications it may also hold certain relevance. We present a comprehensive review of clinoptilolite applications in veterinary and human medicine. Finally, clinoptilolites antioxidant effects and restoration of antioxidant defense mechanisms may also be linked to the positive general systemic impact. Valpoti H., Graer D., Turk R., urii D., Vince S., Folnoi I., et al. 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). This is why no absolute generalization on the mechanisms of action for clinoptilolite materials (tuffs) may be done at this point. When hepatectomized rats were supplemented with a micronized clinoptilolite preparation, Froximun, MDA levels were significantly lower, while liver tissue antioxidant mechanisms were strengthened, as witnessed by a significantly higher activity of Cu-Zn SOD and GSH (Saribeyoglu, 2011). Effects of prolonged consumption of water with elevated nitrate levels on certain metabolic parameters of dairy cattle and use of clinoptilolite for their amelioration. Removal of zinc, copper and lead by natural zeolite a comparison of adsorption isotherms. They have shown protective effects of clinoptilolite on hematocrit and hemoglobin levels as well as on cadmium levels in the liver of pigs fed with cadmium in the presence of clinoptilolite in comparison to animals fed only with addition of cadmium to the diet. Magnetic nano/micro-particles based on clinoptilolite-type of natural zeolite (CZ) were fabricated and were expected to act as carriers for controlled drug delivery/release, imaging and local . Therefore, it is possible that the contact between clinoptilolite and tumor cells with increased hydrogen peroxide concentrations induces formation of free radicals; therefore, increases in the oxidative burden occur in tumor cells, which consequently die. Effects of clinoptilolite treatment on oxidative stress after partial hepatectomy in rats. Jahanbakhsh S., Kabore K. P., Fravalo P., Letellier A., Fairbrother J. M. (2015). Interestingly, in the pH 3 and higher Pb, the leakage was less than 1%, while at pH 1 the leakage was observed up to 20% of the initial lead content. Natural zeolite clinoptilolite: new adjuvant in anticancer therapy (1990), or as Co2+> Cu2+> Zn2+> Mn2+ by Erdem et al. Diaz-Sanchez S., DSouza D., Biswas D., Hanning I. Montinaro M., Uberti D., Maccarinelli G., Bonini S. A., Ferrari-Toninelli G., Memo M. (2013). 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). 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. Similarly, antiviral properties for clinoptilolite in vitro were shown on the human adenovirus 5, herpes simplex virus type 1, and the human enteroviruses coxsackievirus B5 and echovirus 7 (Grce and Paveli, 2005). (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. Surfactant modified zeolites as a drug-carrier and the release of chloroquin. but also by the material composition and cation affinity properties. Similar results were, however, observed in animals supplemented with vitamins E and C as well (Madhusudhan et al., 2009). 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). The role of Na/K-ATPase signaling in oxidative stress related to obesity and cardiovascular disease. MambaI B. Documented properties and effects of clinoptilolite relevant for biomedical applications and effects in animals and humans. It also reduced lipid peroxidation in the liver of mice.The experiments were performed on various tumor cell cultures and tumor-bearing animals . The majority of studies on clinoptilolite were done by using different, so-called activated materials to increase either the surface area or to improve the clinoptilolite general adsorption or the ion-exchange capacity. Clinoptilolites positive immunomodulatory effects in similar conditions may be due to the interactions of clinoptilolite particles in the intestine with microfold cells (M-cells) (Figure (Figure3).3). Their molecular structure is a dense network of AlO4 and SiO4 that generates cavities where water and other polar molecules or ions are inserted/exchanged. The observed local immunomodulatory effects of clinoptilolite involve the induction of immune responses through Peyers patches and/or possible positive effects on microbial intestinal populations through still unknown mechanisms. Beltcheva M., Metcheva R., Popov N., Teodorova S. E., Heredia-Rojas J. Zeolite clinoptilolite is a volcanic mineral that can successfully transform your health science has proven that zeolite can have many positive effects on you, from detoxification to strengthening the immune system. This work presented the studies with the natural zeoliteclinoptilolite as the catalyst for the isomerization of geraniol. 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. 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. Clinoptilolite tuff released particles are denoted by C. M-cells are hypothesized to transport luminal clinoptilolite tuff released particles across the epithelial barrier and present them to immunological cells (e.g., dendritic cells) in the lamina propria and the Peyers patches. 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). The basic structure of clinoptilolite is considered to be biologically neutral and non-toxic (Auerbach et al., 2003). For example, selectivity alignments of the zeolite clinoptilolite cation exchange have been given as Ba2+> Cu2+, Zn2+> Cd2+, Sr2+> Co2+ by Blanchard et al. Indeed, the microbiota-clinoptilolite interaction may also underlie the observed immunomodulatory mechanism as well. From: Microsized and Nanosized Carriers for Nonsteroidal Anti-Inflammatory Drugs, 2017 Related terms: Ammonium Aflatoxin Inorganic Ions Surfactants Silicon Dioxide Effect of zeolite (clinoptilolite) as feed additive in Tunisian broilers on the total flora, meat texture and the production of omega 3 polyunsaturated fatty acid. 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). (2015). For example, both clinoptilolite and clay materials may be used for ion-exchange reactions. Bingham S., colonic protein metabolism and colorectal cancer. Still, no direct data supports these assumptions that may partially explain the observed effects on the oxidative stress defense mechanisms, which are visible as activation or restoration of activity and levels of natural antioxidant enzymes. (2002). (2015). Indeed, ROS induces cell and tissue damage when the inflammation is initiated as a mechanism for restoration of the bodys homeostasis. 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). Zeolite Clinoptilolite: Therapeutic Virtues of an Ancient Mineral 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. They are interconnected with ROS and activity of Nrf2 (Paveli et al., 2001b; Katic et al., 2006). Classical acute, subacute, and chronic tests on rats and mice were performed as well. Petrakakis Y., Mylona E., Georgantas D., Grigoropoluou H. (2007). 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). In this study, endurance-trained subjects were recruited and supplemented with a clinoptilolite/dolomite/maca-based product (Panaceo Sport). Clinoptilolite has been shown to be an effective material for the sorption of Cs and Sr ( Colella, 1999 ), whilst also reducing leaching ( Spence and Shi, 2004 ). Toxicity of lead: a review with recent updates. In Zeolite A, the Al-framework is balanced out by the maximum number of cation exchange sites; it has high cation contents and superior exchange capacities. These changes in the M-cells then affect the Peyers patches as well. Jurki L. M., Cepanec I., Paveli S. K., Paveli K. (2013). Hayyan M., Hashim M. A., AlNashef I. M. (2016). This central clinoptilolite characteristic related to elimination of toxic agents, which may be seen as a support to the body homeostasis, could be widely exploited in a number of medical applications. Clinoptilolite as a natural, active zeolite catalyst for the chemical Any impairment of the host immune and inflammatory mechanisms in the long-term may cause other inflammatory disorders, e.g., chronic sinusitis, otitis media and osteomyelitis, or microbial overgrowth syndromes, such as bacterial vaginosis, or inflammatory bowel disorders. This decrease in harmful metal concentrations was a result of the clinoptilolite detoxification function and probable restoration of the body mineral metabolism homeostasis (Zhakov, 2003). Characterization of kaolin dispersion using acoustic and electroacoustic spectroscopy. Novel, oxygenated clinoptilolite material efficiently removes aluminium from aluminium chloride-intoxicated rats in vivo. Impact of medicated feed along with clay mineral supplementation on, Application of zeolite in biomedical engineering: a review, in. For instance, regular moderate exercise increases the resistance against oxidative stress, while acute and vigorous exercise can generate free radicals in excess. Effects of dietary inclusion of a zeolite (Clinoptilolite) on performance and protein metabolism of young growing pigs. Moreover, in cases where diarrhea symptoms were removed and the pathogenic agent was identified upon Enterex treatment antibiotics were additionally used to completely eliminate pathogenic bacteria from the intestinal lumen (Rodrguez-Fuentes et al., 1997). An interesting effect of clinoptilolite was observed in fluoride-intoxicated rats (Madhusudhan et al., 2009). Zeolite For Cats & Dogs - Advice, Guidance and Support. 1.Summary Recent data indicate the beneficial effects of modified natural zeolite.