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Aperito Journal of Drug Designing and Pharmacology http://dx.doi.org/10.14437/2378-8968-2-113 Review Received: May 08, 2015 Accepted: Jun 19, 2015 Published: Jun 22, 2015 Sinan Ince, Aperito J Drug Design Pharmacol 2015, 2:1 An Update on Health Effects of Metalloid Trace Element: Boron Sinan Ince1* and Damla Arslan-Acaroz2 1 Afyon Kocatepe University, Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, 03030 Afyonkarahisar, Turkey 2 Afyon Kocatepe University, Faculty of Veterinary Medicine, Department of Biochemistry, 03030 Afyonkarahisar, Turkey micronutrient for the growth and viability of plants. The Abstract Boron (B), an element with the atomic number 5 in primary source of B for human and animal nutrition is the periodic table, found in the earth’s crust. In the vegetable products, the highest B contents found in fruits surroundings, it is a ubiquitous element combined with and legumes. Although, the biochemical mechanism of B is oxygen to form compounds that are called borates. It is not not wholly known yet. However, B is determined to be an present on the universe in its elemental form which is found essential element of human and animals and is present in only in compounds. Widespread borate compounds are boric their tissues at low concentrations. According to this acid, sodium tetraborates that are also referred as borax, and knowledge, B is mainly investigated in terms of its effects boron oxide. Borates are found in nature in soils, rocks, on metabolism, diseases, and assessed its potential risks. In surface water, and ocean water. Seven to eighteen percent of this review, we summarized usage of B, and its effects on environmental B derives from several “anthropogenic” cancer, antioxidant status and assessment of its risks. sources (fertilizers, releases of a wastewater treatment plant, Keywords: Boron; Boron compounds; Cancer; Antioxidant and a waste of coal-fired power plants ash). B is used in status; Risk assessment many industrial areas which include glass, ceramics, soaps, * bleaches, detergents, fire retardants, cosmetics, and agriculture. For this reason, its exposure is inevitable, its benefits and risk assessments are still performing. For decades, it has been known that B is an essential Corresponding Author: Sinan INCE, Ph.D Afyon Kocatepe University, Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, 03030 Afyonkarahisar-Turkey; Tel: +90272281312-16142; Fax: +90272281349; E-mail: [email protected], [email protected] Introduction Boron (B) is a unique and exciting element. Also, it supplementation may have significant effects on diverse shows many similarities to carbon, a neighbor of B in the metabolic and physiological systems of the organism [4]. periodic table, and silicon. At the same time, B has two Studies have demonstrated that B has effects on the naturally occurring isotopes [1]. Approximately there are metabolism of minerals (Ca and P) [5], vitamin D [6], 230 kinds of B mineral, and they are not found in elemental enzymes form in nature [2]. B is a trace mineral for plants, animals, cytochrome b5 reductase) [6, 3], hormones (insulin, and humans [3]. Findings suggest that in animal and human estrogen, testosterone, T3, T4) [7, 8, 9], and reactive oxygen nutrition, physiological amounts of dietary boron B species develops [10]. Also, B plays an important (aldehyde dehydrogenase, xanthine oxidase, Copyright: © 2015 AJDDP. This is an open-access article distributed under the terms of the Creative Commons Attribution License, Version 3.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Volume 2 • Issue 1 • 113 www.aperito.org Citation: Sinan Ince et al. (2015), An Update on Health Effects of Metalloid Trace Element: Boron. Aperito J Drug Design Pharmacol 2:113 http://dx.doi.org/10.14437/2378-8968-2-113 Page 2 of 6 role in plasma lipid profiles, brain function and improving and humans [21, 22]. B is not metabolized and is excreted arthritis [3, 11]. A diet with low B has been observed to lead from body through urine. It does not appear to accumulate in to a number of general health problems and to increase soft tissue, but in bones [23]. cancer risk. The most frequent signs of B deficiency include By now, two possible hypotheses present the mechanism of arthritis, memory loss, osteoporosis, degenerative and soft B in animals and humans. First, B may have a role in cell– cartilage diseases, hormonal disequilibria and a reduction in membrane, influence responses to hormone action, the libido [12]. transmembrane signalling and movement of regulatory ions Boron sources and its usage [6]. Second, B may act as a metabolic regulator in several Mineral resources of a country provide not only enzymatic systems [7]. Also, boronated agents could have politic but also economic advantages. B has strategic ability to decrease lipid levels, inhibit inflammation and importance and its reserves of world principally found in regulate proliferation of cells [11]. At the same time, B Turkey, the United States, Argentina, Peru, Russia, and limits oxidative damage by enhancing body stores of China. Turkey has the largest boron reserves, and 72% of glutathione and by inhibiting other ROS [24]. total world reserves are located in Turkey [13, 14, 15]. Boron and Cancer Important boron compounds are borax (tincal), kernite, Cancer causes to death worldwide than many pandermite, ulexite, colemanite and hydroboracite [16]. B is diseases such as AIDS, tuberculosis and malaria [25]. Until an important component of cosmetics, pharmaceuticals and now, B and its compounds are widely used and it is included is necessary for a variety of industrial processes. In cosmetic in the treatment of cancer. Recent epidemiological studies, goods, it is used as a preservative, antiseptic, water softener, which are based on the relation between prostate cancer and pH adjuster, emulsifier, neutralizer, or buffer. It is also used boron as a dietary factor, have shown that men who in the production of cement, crockery, porcelain, enamels, consume higher levels of boron have a lower risk of prostate glass, leather, carpets, and soaps. Additionally, it is used as cancer [26]. Gallardo-Williams et al. [27] demonstrated that medicinal astringent, eyewashes, and antiseptic for the boric acid reduced the growth of prostate tumors in mice as treatment of burns [17]. Blech et al. [18] reported that well as the level of prostate specific antigen. treatment with a 3% boric acid solution markedly improves In human blood cell cultures, It is reported that the healing wounds. It is used for the treatment of boron compounds do not show cytotoxic, genotoxic and osteoporosis, allergic diseases, arthritis, and to treat brain mutagenic potential [28, 29, 30]. Long-term, 2-year studies, cancer [19]. B is used more than 400 areas [17, 20] and day did not demonstrate a carcinogenic effect in Sprague- by day its usage area is increasing. Dawley rats [31]. Benson [32] reported that short-term Distribution, elimination, and metabolism of boron mutagenicity studies clearly revealed that boron compounds B is absorbed rapidly from the gastrointestinal tract are not genotoxic. Boric acid was found negative for into the blood stream after its administration and swiftly mutagenicity in the Salmonella typhimurium assays. In distributed throughout the body via passive diffusion. accordance with this [33] stated that boric acid also shows Following the administration of B, concentration of it in the insignificant potential for genotoxicity in bacteria and blood and tissue is reported to be in the ratio of 1:1 in rats cultured mammalian cells. Volume 2 • Issue 1 • 113 www.aperito.org Citation: Sinan Ince et al. (2015), An Update on Health Effects of Metalloid Trace Element: Boron. Aperito J Drug Design Pharmacol 2:113 http://dx.doi.org/10.14437/2378-8968-2-113 Page 3 of 6 In the boron neutron capture therapy, B compounds system as well as an inhibition of LPO. Boric acid particularly boric acid has been prevalently used for significantly decreased the level of malondialdehyde in the different types of cancer [34, 35, 36]. With this treatment, liver of CCl4 intoxicated mice. In contrast, it increased GSH only tumor cells are targeted and applied without excessive content, as well as the activities of SOD and CAT in the radiation to healthy cells. The tumor-selective delivery of B liver [42]. by liposomes or other biodistribution techniques has been Risk assessment of boron demonstrated as a very useful means to increase B Compounds of B is used in many industries which concentrations in the tumor tissues [37, 38]. These studies include cosmetics and pharmaceuticals and is also used in show that B has potential anti-cancer effects on cancer cells numerous industrial processes. Therefore daily B intake and it may be used for the treatment of many cancer types. varies because it is found in many sources. Risk assessment Boron and antioxidant status of B evaluated in terms of the most recent toxicological and Boron is able to strengthen the antioxidant defense pharmacokinetic researches. In rat toxicity study in which system of tissues by means of an unidentified mechanism the NOAEL was defined as 9.6 mg B/kg/day. A reference may involve changes in oxidative metabolism [39, 40]. Ince dose was detected as 0.3 mg B/kg/day and an acceptable et al. [24] reported that B supplementation (100 mg/kg) in daily intake of 18 mg B/day. High doses of B intake causes diet decreases lipid peroxidation, whereas enhances the infertility particularly effect on male reproductive system antioxidant defense mechanism, liver Glutathione (GSH) and disorder of bone metabolism in infant [43]. concentration and vitamin status of rats. B deficiency Conclusion increases the concentration of Superoxide Dismutase (SOD), Recently in addition to industrial areas, B is used in Catalase (CAT), and peroxidase in Anabaena PCC 7119 medicine. B has many pharmacological effects such as heterocysts [41]. In addition, Turkez et al. [28] determined regulator of metabolism, cancer suppressor and antioxidant that 15 mg/L B compounds increased both SOD and CAT activity. It is predicted that B compounds are going to bring activities, while 500 mg/L B decreased both SOD and CAT novel treatment methods. It is inevitable that B containing activities in erythrocytes. Pawa and Ali [40] reported that drugs or treatment methods for many diseases needed to when 4 mg/ kg borax was inhibited thioacetamide (400 develop. mg/kg) induced oxidative stress parameters and B could help References to maintain the oxidant/antioxidant balance of the affected 1. tissue. Greenwood N.N., Earnshaw A. (1984) Chemistry of the Elements. Pergamon Pres, New York; Administration of different dosage of B (5, 10 and 20 mg/kg, respectively) in a dose-dependent manner pp:139-140. 2. reversed malathion-induced (100 mg/kg) oxidative stress, lipid peroxidation and antioxidant enzyme activity [10]. Kemp P.H. (1956). The Chemistry of Boraks, Part 1, Borox Consolidated limited, S.W.I. London. 3. Devirian T.A., Volpe S.L. (2003) The physiological Boric acid has hepatoprotective effect may be caused both effects of dietary boron. Crit Rev Food Sci Nutr; by an increase in the activity of the antioxidant defence 43; 219-231. Volume 2 • Issue 1 • 113 www.aperito.org Citation: Sinan Ince et al. (2015), An Update on Health Effects of Metalloid Trace Element: Boron. Aperito J Drug Design Pharmacol 2:113 http://dx.doi.org/10.14437/2378-8968-2-113 4. 5. Page 4 of 6 Hunt C.D. (1994) The biochemical effects of 12. Scorei R., Popa R. (2010) Boron-containing physiologic amounts of dietary boron in animal compounds as preventive and chemotherapeutic nutrition models. Environ Health Perspect; 102; 35- agents for cancer. Anti-Cancer Agents in Medicinal 43. Chemistry; 10; 346–351. Meacham S.L., Taper L.J., Volpe S.L. (1994) 13. Velioğlu S., Şaylı B.S., Altunsoy S. (1999) Bor Effects of boron supplementation on bone mineral madeni havzalarında üretilen bazı gıdalarda bor density and dietary, blood, and urinary calcium, miktarının belirlenmesi üzerine bir araştırma. Gıda;. phosphorus, magnesium, and boron in female 24; 13-19. 14. Velioğlu S., Şimşek A. (2003) İnsan sağlığı ve athletes. 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Cancer Causes Control; 18; 71-77. Volume 2 • Issue 1 • 113 www.aperito.org Citation: Sinan Ince et al. (2015), An Update on Health Effects of Metalloid Trace Element: Boron. Aperito J Drug Design Pharmacol 2:113 http://dx.doi.org/10.14437/2378-8968-2-113 Page 5 of 6 21. Murray F.J. (1998) A comparative review of the 29. Geyikoğlu F., Türkez H., Keles M.S. (2005). The pharmacokinetics of boric acid in rodents and role of fruit juices in the prevention of aluminum humans. Biol. Trace Elem Res 66; 331–341. sulphate toxicity in human blood in vitro. Fres 22. Usuda K., Kono K., Orita Y. (1998) Serum and Environ Bull; 14; 878-883. urinary boron levels in rats aft er single 30. Turkez H., Tatar A., Hacımuftuoglu A., Ozdemir E. administration of sodium tetraborate. Arch Toxicol (2010) Boric acid as a protector against paclitaxel 72; 468-474. genotoxicity. Acta Biochimica Polonica; 57; 95–97. 23. Moseman R.F., (1994) Chemical disposition of 31. Weir R., Fisher, R. 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(2011) 34. Martin R.F., D’Cunha G., Pardee M., Allen B.J. Prevalence of prostate cancer in high boron- (1989) Induction of DNA double-strand breaks by exposed population: a community-based study. Biol 157Gd neutron capture. Pigment Cell Res; 2; 330– Trace Elem Res; 144; 49-57. doi: 10.1007/s12011- 332. 011-9023-z 35. Gregoire V., Begg A.C., Huiskamp R., Verrijk R., 27. Gallardo-Williams M.T., Chapin R.E., King P.E., Bartelink H. (1993) Selectivity of boron carriers for Moser G.J., Goldsworthy T.L. (2004) Boron boron neutron capture therapy: pharmacological supplementation inhibits the growth and local studies expression bronophenylalanine of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice. Toxicol Pathol; 32; 73–78. with borocaptate and sodium, boric acid Lin murinetumors. Radiother Oncol; 27; 46–54. 36. Primus F.J., Pak R.H., Richard-Dickson K.J., Szalai 28. Turkez H., Geyikoglu F., Tatar A., Keles S., Ozkan G., Bolen J.L. Jr., Kane R.R., Hawthorne M.F. A. (2007) Effects of some boron compounds on (1996) Bispecific antibody mediated targeting of peripheral human blood. Z Naturforsch; C 62; 889– nido-carboranes to human colon carcinoma cells. 896. Bioconjug Chem; 7; 532–535. Volume 2 • Issue 1 • 113 www.aperito.org Citation: Sinan Ince et al. (2015), An Update on Health Effects of Metalloid Trace Element: Boron. Aperito J Drug Design Pharmacol 2:113 http://dx.doi.org/10.14437/2378-8968-2-113 37. Hawthorne M.F., Shelly K., (1997) Liposomes and drug delivery vehicles for boron agents. J Neurooncol; 33; 53–58. Page 6 of 6 associated with the oxidative stress. Chem-Biol Inter; 160; 89–98 41. Garcia-Gonzalez M., Mateo P., Bonilla I. (1991) 38. Wang P., Zhen H., Jiang X., Zhang W., Cheng X., Boron requirement for envelope structure and Guo G., Mao X., Zhang X. (2010) Boron neutron function in Anabaena PCC 7119 heterocysts. J Exp capture therapy induces apoptosis of glioma cells Bot; 42; 925–929. through Bcl-2/Bax. BMC Cancer; 10; 661-671. 42. Ince S., Keles H., Erdogan M., Hazman O., 39. Hunt C.D, Idso J.P. (1999) Dietary boron as a Kucukkurt I. (2012) Protective effect of boric acid physiological regulator of the normal inflammatory against carbon tetrachloride-induced hepatotoxicity response: a review and current research progress. J in mice. Drug Chem Toxicol; 35; 285–292. Trace Elem Exp Med; 12; 221–233. 43. Murray F.J. (1995) A Human Health Risk 40. Pawa S., Ali S. (2006) Boron ameliorates fulminant Assessment of Boron (Boric Acid and Borax) in hepatic failure by counteracting the changes Drinking Water. Regulatory Toxıcology And Pharmacology; 22; 221–230. Volume 2 • Issue 1 • 113 www.aperito.org