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Aluminium Toxicosis: a Review of Toxic Actions and Effects

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Aluminium Toxicosis: a Review of Toxic Actions and Effects Interdiscip Toxicol. 2019; Vol. 12(2): 45–70. interdisciplinary doi: 10.2478/intox-2019-0007 Copyright © 2019 SETOX & IEPT CEM SASc. This is an Open Access article distributed under the terms of the Creative Commons Attri- bution-NonCommercial-NoDerivatives 4.0 License (https://creativecommons.org/licenses/ by-nc-nd/4.0). REVIEW ARTICLE Aluminium toxicosis: a review of toxic actions and effects Ikechukwu Onyebuchi IGBOKWE 1, Ephraim IGWENAGU 1, Nanacha Afifi IGBOKWE 2 1 Department of Veterinary Pathology, Faculty of Veterinary Medicine, University of Maiduguri, Maiduguri, Nigeria 2 Department Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Maiduguri, Maiduguri, Nigeria ITX120219A01 • Received: 22 November 2018 • Accepted: 29 August 2019 ABSTRACT Aluminium (Al) is frequently accessible to animal and human populations to the extent that intoxications may occur. Intake of Al is by inhalation of aerosols or particles, ingestion of food, water and medicaments, skin contact, vaccination, dialysis and infusions. Toxic actions of Al induce oxidative stress, immunologic alterations, genotoxicity, pro-inflammatory effect, peptide denaturation or transformation, enzymatic dysfunction, metabolic derangement, amyloidogenesis, membrane perturbation, iron dyshomeostasis, apoptosis, necrosis and dysplasia. The pathological conditions associated with Al toxicosis are desquamative interstitial pneumonia, pulmonary alveolar proteinosis, granulomas, granulomatosis and fibrosis, toxic myocarditis, thrombosis and ischemic stroke, granulo- matous enteritis, Crohn’s disease, inflammatory bowel diseases, anemia, Alzheimer’s disease, dementia, sclerosis, autism, macrophagic myofasciitis, osteomalacia, oligospermia and infertility, hepatorenal disease, breast cancer and cyst, pancreatitis, pancreatic necrosis and diabetes mellitus. The review provides a broad overview of Al toxicosis as a background for sustained investigations of the toxicology of Al compounds of public health importance. KEY WORDS: aluminium; intoxication; pathology; toxicity; toxicosis Introduction Aluminium (Al) is the most widely distributed metal in to high levels of Al (Sorgdrager et al., 1998; Vandenplas et the environment (Delhaize and Ryan, 1995; Ranjbar et al., al., 1998; Boran et al., 2013). 2008; Exley and House, 2011) occurring naturally in the Several chemical compounds with Al are in extensive trivalent state (Al+3) as silicates, oxides and hydroxides, use in various products and processes associated with but may combine with other elements such as chlorine, human activities. These compounds are Al chloride, Al sulphur, fluorine, as well as form complexes with organic hydroxide (alumina trihyrate), Al nitrate, Al phosphate, matter (Jones and Bennet, 1986; Ganrot, 1986; Martin, Al sulfate (alum), Al potassium (potash alum), Al ammo- 1992). Environmental media may be contaminated by Al nium sulfate (ammonium alum) and Al silicate (Anon, from anthropogenic sources and through the weathering 1982; Lewis, 2001). The compounds are used in crude of rocks and minerals. Weathering processes on rocks oil refining and cracking of petroleum; manufacturing release more Al to the environment than human-related of cooking utensils and foils, parchment paper, printing activities (Lantzy and MacKenzie, 1979). Exposures to ink, glass, ceramics, pottery, incandescent filaments, Al occur in occupations associated with mining and fireworks, explosives, photographic flashlight, electric processing of ore, scrap metal recycling, deployment insulators, cement, paints and varnishes, fumigants and and use of Al-containing compounds and products, and pesticides, lubricants, detergents, cosmetics, pharma- during engagement in Al metal cutting, sawing, filing and ceuticals (drugs), vaccines, as well as in water treatment welding. Animals and humans living in environments and purification, treating sewage and fur, tanning leather, contaminated by industrial wastes may also be exposed waterproofing clothes and concretes, industrial filtration, hemodialysis, measuring radiation exposure, in products as flame retardant and fireproofing, anticorrosion agent, food additives to prevent caking as well as components Correspondence address: of baking powders and colorants (Anon, 1982, 2008a; Ikechukwu Onyebuchi Igbokwe, DVM, MVSc, PhD, FCVSN Malakoff, 2000; Lewis, 2001; Soni et al., 2001; Saiyed and Faculty of Veterinary Medicine, University of Maiduguri, Strategic Animal Research Group Yokel, 2005). P O Box 8000, Maiduguri, Nigeria The Al ion has no physiological role in metabolic e-mail: [email protected]; [email protected] processes (Exley and House, 2011) but it can be a metallic 46 Aluminium toxicosis Ikechukwu Onyebuchi Igbokwe, Ephraim Igwenagu, Nanacha Afifi Igbokwe toxicant to humans and animals (Becaria et al., 2002) discovered to have focused on Al toxicity of one system when there is high body burden of the metal after natural of the body in each review, covering the scope of nervous, or unnatural exposure (Exley, 2013). Al was considered reproductive, respiratory, mammary, skeletal and immune unsafe to humans after the discovery of increased levels tissue toxicities. One review addressed the toxicities in of Al in brain tissues of patients with encephalopathy, bone, hematopoietic tissue and kidney (Jeffrey et al., 1996) having been exposed to Al accumulation through dialysis and another summarized the physiological alterations in (Alfrey and Solomons, 1976). Toxicosis due to Al accumu- the musculoskeletal, respiratory, cardiovascular, hepatobi- lation in mammalian tissues was associated with various liary, endocrine, urinary and reproductive systems(Nayak, pathologic effects (Wills and Savory, 1983; Kaiser et al., 2000). Thus the question raised was whether Al toxicosis, 1984; Boyce et al., 1986; Drüeke et al., 1986; Hewitt et al., as a disease entity, existed in the literature with cur- 1990; Bushinsky et al., 1995; Reinke et al., 2003; Abubakar rent research information. The literature search for Al et al., 2004; Bogdanović et al., 2008; Yousef and Salama, toxicosis as a narrative review (Green et al., 2006) with 2009; Khattab et al., 2010; Blaylock, 2012; Buraimoh and a broad thematic approach was unproductive and this Ojo, 2013; Sumathi et al., 2013). Recent reviews on toxic observation justified the need for the current review. effects of Al covered reproductive toxicity (Mouro et al., Toxicosis associated with Al exposure is the pathologi- 2017), pulmonary lesions (Kongerud and Søyseth, 2014; cal condition or disease caused by the toxic actions of Al Taiwo, 2014), impact on the breast (Darbre, 2016), bone and its compounds. The literature search was intended abnormalities (Chappard et al., 2016; Klein, 2019), immu- to collate, synthesize and integrate the published reports notoxity (Zhu et al., 2014a) and neurologic disorders on the subject matter without meta-analysis and critical (Colomina and Peris-Sampedro, 2017; Morris et al., 2017). evaluation of published data. For this review, the major This review is an abridged and global overview of toxic themes for the literature search under the title included effects of Al and its compounds, covering some relevant exposure modalities, toxic actions and effects in cells, aspects of exposure and updated systemic toxicosis in tissues and systems of the body (Figure 1). These themes humans and animals, relevant as background for prospec- provided the key words and phrases for the internet search. tive toxicopathologic studies. The initial search platform was usually GOOGLE.COM with the linked GOOGLE SCHOLAR helping to search related articles. Subsequently, the search was extended to Literature search justification and methods MEDLINE, PUBMED, PMC Europe, RESEARCHGATE, SCOPUS, SCIENCEDIRECT, SAGE, TANDFONLINE The initial goal in our study group was to explore the and SPRINGERLINK. On each platform, an article that role of the ubiquitous Al ion in erythrocyte membrane was found could also have links to related articles and dysfunction (Igbokwe, 2016) and metabolic dysregulation these links were followed to enrich the search outcomes. (Igwenagu, 2017). With the preliminary literature search Every article was read as an abstract or full article after starting in 2013 and looking backwards in time, research downloading to the literature bank. At this stage, “back- publications revealed a myriad of toxic actions of Al caus- ward search” based on references of read articles could ing pathological conditions. Several narrative literature be done and “forward search” was required when new reviews, referred to in the introductory section, were themes emerged that needed further exploration. The Figure 1. Major themes for the literature search on aluminium toxicosis. ISSN: 1337-6853 (print version) | 1337-9569 (electronic version) Interdisciplinary Toxicology. 2019; Vol. 12(2): 45–70 47 Full-text also available online on PubMed Central integration of the literature search processes are illus- trated in Figure 2. Occasionally, article request options Literature were used to obtain restricted publications and the articles Search: HOW were received from authors. The literature collated from the search was read for content comprehension. The body Research Articles: Backward Forward of knowledge was summarized and narrated after cogni- Search Primary (original research) Secondary (review) Search tive reflection and integration to represent the current knowledge of the literature on Al toxicosis. The articles
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