THE EFFECT OF CALCIUM TAINTED WATER ON CADMIUM INDUCED LIVER DAMAGE






INTRODUCTION AND LITERATURE REVIEW
Heavy metals are toxic agent. They are toxic to humans and animals. Heavy metals which establishes toxic actions to humans include; cadmium (Stohs and Bagchi,1995), lead ( Ferner, 2001) and mercury (Hawkes, 1997). Each of these has been studied in isolation for toxicity (Huton and Symon, 1986; Nriagu and Pacyna, 1988; Nriagu, 1989). But, in the eco-system, be it air, atmosphere, land, and water where they occur, they do not exist in isolation. They occur in close association with other metal and non-metallic elemental pollutants. Among the metallic pollutant could be calcium, copper, zinc, magnesium, manganese, iron and others. Metals are known to interact with one another. The interaction can bring two elements together in close proximity or it could cause out right displacement of one another. When ingested together in food and water, they antagonize each other. When it comes to intestinal and pulmonary absorption, it is therefore conceivable that the presence of other elements can the toxic potential of each of the heavy metals that have been studied in isolation.
Eborge (1994) reported that warri river has an unacceptable high cadmium level, 0.3 mg cadmium per liter of water which was 60 folds above the maximum allowable level of 0.005 mg per liter. This report prompted our earlier studies on the hepato, nephro and gonadial toxicity of cadmium. In rats exposed to this high dose via water and diet, the diet was formulated with feed exposed to 0.3 mg cadmium per water. In the ambient water as protein source and the toxic effect investigated and reported (Asagba and obi 2000; Asagba and Obi 2001; Obi and Ilori 2002; Asagba and Obi 2004a; Asagba and Obi 2004b; Asagba and Obi 2005).The study focus on cadmium without taking into consideration the fact that other metals were also present in the river water, and as such were co-consumed by the communities using the river water for cooking drinking and for other domestic purposes. Hence, it is desirable to know if the presence of other metals would enhance or diminish the toxic potential of cadmium or indeed if any other heavy metals such as lead that was mentioned above. Therefore, the aim of the present study was to re-examine the toxic potential of cadmium in the presence of other metals such as calcium and magnesium.
The objectives set out to achieve were;
1. Re-examination of toxicity of using established and those for liver toxicity namely; blood alanine amino transferase and aspartate amino transferase, alkaline phosphatase, bilirubin, albumin and total protein.
2. Re-examine the status parameter in the absence of cadmium but in the presence of calcium or magnesium or both.
3. Re-examine this parameters in the presence of cadmium, calcium and magnesium.
1.1 CADMIUM
Cadmium is a chemical element with symbol Cd and atomic number 48. This soft, bluish-white metal is chemically similar to the two other stable metals in group 12, zinc and mercury. Like zinc, it prefers oxidation state +2 in most of its compounds and like mercury it shows a low melting point compared to transition metals. Cadmium and its congeners are not always considered transition metals, in that they do not have partly filled d or f electron shells in the elemental or common oxidation states. The average concentration of cadmium in Earth's crust is between 0.1 and 0.5 parts per million (ppm). It was discovered in 1817 simultaneously by Stromeyer and Hermann, both in Germany, as an impurity in zinc carbonate. Cadmium occurs as a minor component in most zinc ores and therefore is a byproduct of zinc production. It was used for a long time as a pigment and for corrosion-resistant plating on steel, whereas cadmium compounds were used to stabilize plastic. The use of cadmium is generally decreasing due to its toxicity (it is specifically listed in the European Restriction of Hazardous Substances (Morrow, 2010)) and the replacement of nickel-cadmium batteries with nickel-metal hydride and lithium-ion batteries. One of its few new uses is in cadmium telluride solar panels. Although cadmium has no known biological function in higher organisms, a cadmium-dependent carbonic anhydrase has been found in marine diatoms.
1.1.1 PHYSICAL PROPERTIES
Cadmium is a soft, malleable, ductile, bluish-white divalent metal. It is similar in many respects to zinc but forms complex compounds (Holleman et al., 1985). Unlike other metals, cadmium is resistant to corrosion and as a result it is used as a protective layer when deposited on other metals. As a bulk metal, cadmium is insoluble in water and is not flammable; however, in its powdered form it may burn and release toxic fumes (CSEM, 2011).
1.1.2 CHEMICAL PROPERTIES
Although cadmium usually has an oxidation state of +2, it also exists in the +1 state. Cadmium and its congeners are not always considered transition metals, in that they do not have partly filled d or f electron shells in the elemental or common oxidation states (Cotton, 1999). Cadmium burns in air to form brown amorphous cadmium oxide (CdO); the crystalline form of this compound is a dark red which changes color when heated, similar to zinc oxide. Hydrochloric acid, sulfuric acid and nitric acid dissolve cadmium by forming cadmium chloride (CdCl2), cadmium sulfate (CdSO4), or cadmium nitrate (Cd(NO3)2). The oxidation state +1 can be reached by dissolving cadmium in a mixture of cadmium chloride and aluminum chloride, forming the Cd22+ cation, which is similar to the Hg22+ cation in mercury(I) chloride (Holleman et al., 1985).
Cd + CdCl2 + 2 AlCl3 → Cd2(AlCl4)2
The structures of many cadmium complexes with nucleobases, amino acids and vitamins have been determined (Carballo et al., 2013).
1.1.3 OCCURRENCE

Cadmium metal
Cadmium makes up about 0.1 ppm of Earth's crust. Compared with the more abundant 65 ppm zinc, cadmium is rare (Wedepohl, 1995). No significant deposits of cadmium-containing ores are known. Greenockite (CdS), the only cadmium mineral of importance, is nearly always associated with sphalerite (ZnS). This association is caused by the geochemical similarity between zinc and cadmium which makes geological separation unlikely. As a consequence, cadmium is produced mainly as a byproduct from mining, smelting, and refining sulfidic ores of zinc, and to a lesser degree, lead and copper. Small amounts of cadmium, about 10% of consumption, are produced from secondary sources, mainly from dust generated by recycling iron and steel scrap. Production in the United States began in 1907, (Ayres et al., 2003) but it was not until after World War I that cadmium came into wide use (Plachy, 1998). One place where metallic cadmium can be found is the Vilyuy River basin in Siberia (Fthenakis, 2004).
Rocks mined to produce phosphate fertilizers contain varying amounts of cadmium, leading to a cadmium concentration of up to 300 mg/kg in the produced phosphate fertilizers and thus in the high cadmium content in agricultural soils (Grant and Shepperd , 2008). Coal can contain significant amounts of cadmium, which ends up mostly in the flue dust (Bettinelli et al., 1988).
1.1.4 BIOLOGICAL ROLE
Cadmium has no known useful role in higher organisms, (Hogan, 2010) but a cadmium-dependent carbonic anhydrase has been found in some marine diatoms (Lane et al., 2005). The diatoms live in environments with very low zinc concentrations and cadmium performs the function normally carried out by zinc in other anhydrases. The discovery was made using X-ray absorption fluorescence spectroscopy (XAFS) (Lane et al., 2000).
The highest concentration of cadmium has been found to be absorbed in the kidneys of humans, and up to about 30 mg of cadmium is commonly inhaled throughout childhood and adolescence (Perry et al., 1976). Cadmium can be used to block calcium channels in chicken neurons (Swandulla and Armstrong, 1989). Analytical methods for the determination of cadmium in biological samples have been reviewed (klorz et al., 2013).
1.1.5 ENVIRONMENT
The biogeochemistry of cadmium and its release to the environment has been the subject of review, as has the speciation of cadmium in the environment (Cullen et al., 2013).
1.1.6 CADMIUM POISONING
The bioinorganic aspects of cadmium toxicity have been reviewed (Maret et al., 2013).The most dangerous form of occupational exposure to cadmium is inhalation of fine dust and fumes, or ingestion of highly soluble cadmium compounds. Inhalation of cadmium-containing fumes can result initially in metal fume fever but may progress to chemical pneumonitis, pulmonary edema, and death (Hayes, 2007). Cadmium is also an environmental hazard. Human exposures to environmental cadmium are primarily the result of fossil fuel combustion, phosphate fertilizers, natural sources, iron and steel production, cement production and related activities, nonferrous metals production, and municipal solid waste incineration. Bread, root crops, and vegetables also contribute to the cadmium in modern populations (Mann, 2012). There have been a few instances of general population toxicity as the result of long-term exposure to cadmium in contaminated food and water, and research is ongoing regarding the estrogen mimicry that may induce breast cancer (Mann, 2012). In the decades leading up to World War II, mining operations contaminated the Jinzū River in Japan with cadmium and traces of other toxic metals. As a consequence, cadmium accumulated in the rice crops growing along the riverbanks downstream of the mines. Some members of the local agricultural communities consuming the contaminated rice developed itai-itai disease and renal abnormalities, including proteinuria and glucosuria (Nogawa et al., 2004).
Jinzū River area, which was contaminated with cadmium
The victims of this poisoning were almost exclusively post-menopausal women with low iron and other mineral body stores. Similar general population cadmium exposures in other parts of the world have not resulted in the same health problems because the populations maintained sufficient iron and other mineral levels. Thus, although cadmium is a major factor in the itai-itai disease in Japan, most researchers have concluded that it was one of several factors. Cadmium is one of six substances banned by the European Union's Restriction on Hazardous Substances (RoHS) directive, which bans certain hazardous substances in electrical and electronic equipment but allows for certain exemptions and exclusions from the scope of the law. The International Agency for Research on Cancer has classified cadmium and cadmium compounds as carcinogenic to humans. Although occupational exposure to cadmium is linked to lung and prostate cancer, there is still a substantial controversy about the carcinogenicity of cadmium in low, environmental exposure. Recent data from epidemiological studies suggest that intake of cadmium through diet associates to higher risk of endometrial, breast and prostate cancer as well as to osteoporosis in humans (Julin et al., 2012). A recent study has demonstrated that endometrial tissue is characterized by higher levels of cadmium in current and former smoking females (Rzymski et al., 2014). Although some epidemiological studies show a significant correlation between cadmium exposure and occurrence of disease conditions in human populations, a causative role for cadmium as the factor behind these effects remains yet to be shown. In order to prove a causative role, it will be important to define the molecular mechanisms through which cadmium in low exposure can cause adverse health effects. One hypothesis is that cadmium works as an endocrine disruptor because some experimental studies have shown that it can interact with different hormonal signaling pathways. For example, cadmium can bind to the estrogen receptor alpha, (Fechner et al., 2011) and affect signal transduction along the estrogen and MAPK signaling pathways at low doses (Ali et al., 2010).
Tobacco smoking is the most important single source of cadmium exposure in the general population. It has been estimated that about 10% of the cadmium content of a cigarette is inhaled through smoking. The absorption of cadmium from the lungs is much more effective than that from the gut, and as much as 50% of the cadmium inhaled via cigarette smoke may be absorbed (Friberg, 1983). On average, smokers have 4–5 times higher blood cadmium concentrations and 2–3 times higher kidney cadmium concentrations than non-smokers. Despite the high cadmium content in cigarette smoke, there seems to be little exposure to cadmium from passive smoking. No significant effect on blood cadmium concentrations has been detected in children exposed to environmental tobacco smoke. In the non-smoking part of the population food is the biggest source of exposure to cadmium. High quantities of cadmium can be found for example in crustaceans, molluscs, offals, and algal products. However, due to the higher consumption the most significant contributors to the dietary cadmium exposure are grains, vegetables, and starchy roots and tubers. Cadmium exposure is a risk factor associated with early atherosclerosis and hypertension, which can both lead to cardiovascular disease (Jarup, 1998).

EDITOR SOURCE: The Effect Of Calcium Tainted Water On Cadmium Induced Liver Damage