Effects Of Vitamin Supplementation On Lead Toxicity In Wistar Albino Rats

1.0 Introduction

1.1 Background To The Study

Lead (Pb) is a very toxic heavy metal with adverse impacts ranging from slight alterations of biochemical and physiological systems to serious damage in some vital organs leading to death of the organism (Gagan et al., 2012). It is among the most common heavy metals that cause toxicity to animals and humans (Roberts, 1999). Lead contamination globally has been reported to be due to the increase in its circulation in soil, water, and air as a result of human activities related to industries, food and smoking, drinking water, and other domestic sources (Nriagu and Pacnya, 1988; WHO, 2010b). Levels of lead in the blood that were initially thought to be safe have now been proven to compromise health and cause injury to multiple organs even while overt symptoms are not present (WHO, 2010a).

Lead binds the sulfhydryl groups present in antioxidants and antioxidant enzymes, which are its most susceptible targets (Hultberg et al., 2001) and further depresses glutathione levels by inactivating glutathione-related antioxidant enzymes. It also renders superoxide dismutase and catalase inactive (Ahamed and Siddiqui, 2007). Other deleterious effects of lead include reducing the synthesis of hemoglobin by inhibiting various key enzymes involved in the heme synthesis pathway and also reducing the life span of circulating erythrocytes by increasing the fragility of cell membranes. The combined aftermath of these two processes leads to anemia (Guidotti et al., 2008).
The harmful effects of lead on hematopoietic, renal, reproductive, and central nervous system are mediated mainly through the increased oxidative stress (Kalia and Flora, 2005) which represents a disparity between the production of free radicals and the ability of biological systems to readily abstract the reactive intermediates or to repair the resulting damage (Blokhina et al., 2003). However, antioxidants are substances which, when present at low concentrations as compared to that of the oxidizable substrate, can prevent the oxidation of that substrate (Pietta, 2000). Studies have shown that antioxidants have the capacity to prevent and cure the damage caused by the generation of free radicals in the body (Pietta, 2000).

Many in vivo and in vitro studies have been conducted to determine the exact mechanisms of toxicity of Cd and Pb. The present body of knowledge suggests oxidative stress as one of the critical mechanisms of toxicity of both metals, even though neither of these metals is a Fenton’s metal [7–10]. Other possible mechanisms of toxicity are binding to oxygen, nitrogen, and sulphur ligands, which may affect numerous enzymes and proteins [7,11]; interaction with bioelements [12–14]; inhibition of apoptosis [15]; and changes in DNA structure and the inhibition of damaged DNA repair, which may lead to aberrant gene expression [16–18].

After absorption, Cd and Pb are distributed in the organisms via red blood cells or proteins [19,20]. A major amount of Cd in red blood cells is bound to high-molecular-weight proteins, while a minor amount is bound to hemoglobin [19]. However, when Pb enters the cell, most of it is bound to hemoglobin rather than the membrane of red blood cells [21]. The hematopoietic system is one of the most sensitive systems and blood represents not only the mode of transportation, but also the critical toxicity target of Cd and Pb [21,22]. Both metals may lead to anemia by various mechanisms [2,10,23]. Cadmium and Pb are transported to the liver, in which they can cause damage and disturbed function. Liver damage can be confirmed by histopathological findings and is often accompanied by increased blood enzyme levels and reduced protein synthesis [24–28]. Toxic effects on kidneys are represented through the structure damage of kidneys and changes in the excretory function [24,25,28,29]. In addition to the metal-toxicity observed in the hematopoietic system, liver, and kidneys, metals have been implicated in various other organ toxicity. Cadmium has been shown to exert toxicity in pancreas, endocrine, cardiovascular, immune, and reproductive systems [1,3,30–32], while Pb toxicity has been linked to toxic effects on the nervous, cardiovascular, and reproductive systems [2,10,21,33]. The majority of the Pb body burden is in mineralizing tissues (bones and teeth) [34]. The fact that Cd and Pb have a comparable radius to Ca ions means that both toxic metals can lead to bone damage by displacing Ca ions [11,35]. The International Agency for Research on Cancer (IARC) has classified Cd as carcinogenic to humans (Group 1), while inorganic Pb has been classified as probably carcinogenic to humans (Group 2A) based on limited evidence in humans and sufficient evidence in animals [21,22,36].

Humans are exposed to mixtures of chemicals rather than an individual chemical, and therefore, it is important to establish whether chemical mixtures produce a more pronounced effect compared to individual chemicals. The importance of the evaluation of ”cocktail effects“ has been summarized in the European Commission statement, which highlighted that even low-level exposure to a complex cocktail of pollutants over decades could have a significant effect on the health status of European citizens [37]. The co-exposure to Cd and Pb may implicate possible synergism or antagonism, additive, or new effects that are not observed for single metal exposure [7,38]. A sub-chronic oral toxicity study with different Cd and Pb doses showed that the main target organs were the blood, liver, and kidneys [24]. Fifteen days following the intraperitoneal administration (i.p.) of a Cd and Pb mixture, Pillai et al. [39] reported that Cd was the more reactive of the two metals, while Masso et al. [40] suggested a possible antagonistic effect between Cd and Pb. Clearly, the interactions between the two metals in a combined mixture are complex and warrant further investigation.

1.2 Statement Of Problem

Lead, a non-physiological heavy metal, is one of the first metals used by man. Its wide application was begun since over 8000 years ago. The absorbed lead is conjugated in the liver and passed to the kidneys, where part of it is excreted in the urine and the rest of absorbed lead accumulates in various body organs, affecting many biological functions at the molecular, cellular and intercellular levels. Ascorbic acid is well known for its antioxidant activity, acting as a reducing agent to reverse oxidation in liquids. When there are more free radicals (ROS) in the human body than antioxidants, the condition is called oxidative stress. The present work aimed to evaluate the effect of vitamin supplementation on lead toxicity in wistar albino rats.

1.3 Objectives Of The Study

The main aim of this study is to evaluate the effect of vitamin supplementation on lead toxicity in wistar albino rats.