Electrolytes Alterations in Some Organs due to Lead Exposure

Okediran B Samuel*, Sanusi F and Suleiman K Yusuf

and Biochemistry, University of Ilorin, Ilorin, Nigeria, Tel: +2348034241610; Email:

okediranbabatunde@gmail.com lead acetate.

four, eight and twelve weeks.

showed different patterns of variations which were dose and time dependent.

organs thus interfering with electrolytes metabolism resulting in deterioration of cellular functions.

Keywords: Lead; Electrolytes; Blood; Liver; Kidney

Introduction

Lead is a poisonous metal, which exist in both organic (Tetraethyl lead) and inorganic (lead acetate, lead chloride) forms in the environment [1]. It has been used in medicines, paintings, pipes, ammunition and in more recent times in alloys for welding storage materials for chemical reagents [2]. Exposure to lead is from numerous sources and a myriad of pathways including air, food, dust, soil and water [3]. Lead has very high affinity for red blood cells, it has been shown that lead inhibits the enzymes-aminolevulinic acid dehydratase (ALAD) and ferrochelatase of the hem synthetic pathway thus preventing conversion of ALA to porphobilinogen and inhibits incorporation of iron into the protoporphyrin ring respectively. This results in reduced hem synthesis and elevated levels of the precursor-aminolevulinic acid (ALA), which is a weak gamma-amino butyric acid (GABA) agonist that decreases GABA release by presynaptic inhibition [4, 5]. Electrolytes are present in body tissues and body fluids and are necessary for the maintenance of physiochemical conditions like secretion of hydrochloric acid in stomach, blood coagulation, bone matrix, membrane potential, bioluminescence and blood pressure which are essential for life. Electrolytes are structural components of body soft tissues like liver, muscle and also participate in acid-base balance and are components of blood buffers.

Approximately 90% of absorbed lead is reported to be stored in the bone with a half-life of 600 - 3000 days. The remaining 10% is stored in soft tissues like kidney, liver and brain. The half-life of lead in these tissues ranges from 40 - 50 days [6]. Lead is conjugated in the liver and passed to the kidney, where a small quantity is excreted in urine and the rest accumulates in various body organs, affecting many biological activities at the molecular, cellular and intercellular levels, which may result in morphological alterations that can remain even after lead levels have fallen [7, 8, 9]. Lead toxicity is closely related to it accumulation in various tissues and it interference with the electrolytes that hamper several physiological processes [10].

Hence, this present study is to determine some electrolytes such as sodium, potassium, calcium and magnesium in some organs such as liver, kidney, spleen and brain of male Albino rats treated with graded doses of lead for a period of four, eight and twelve weeks.

Results

The mean blood lead concentrations of male Wistar rats treated with graded doses of lead for a period of four, eight and twelve weeks are shown in Table 1. There was a significant increase (p<0.05) in blood lead concentrations in the treated groups compared to the control group. The

400ppm treated group had the highest blood lead concentration irrespective of the duration of lead treatment. The group treated with 400ppm for four weeks had blood lead concentration of 19.76 ± 0.47µg/dl which was about 9.2 times higher than that of the control, while those treated for eight weeks had blood lead concentration of 39.82±1.14µg/dl and those treated for twelve weeks had blood lead concentration of 63.50 ± 1.65µg/dl which was about 9.9 times higher than that of the control.

Table 3 shows the liver, kidney, spleen and brain sodium concentrations of male Wistar rats treated with graded doses of lead for a period of four, eight and twelve weeks. In the liver, there was significant increase in sodium concentration most especially in the groups Okediran B Samuel, et al. Electrolytes Alterations in Some Organs due to Lead Exposure. Adv Clin Toxicol 2019, 4(1): 000150.

exposed to 200ppm and 300ppm of lead, except at twelve weeks of treatment where there was significant (p<0.05) decrease. In the kidney, there was no significant change in the sodium concentration for the duration of four weeks of treatment, however there was significant (p<0.05) increase in kidney sodium concentration at 300ppm and 400ppm of lead for eight and twelve weeks of treatment. In the spleen there was significant decrease in the sodium concentration throughout the duration of treatment. In the brain, there was significant increase in sodium concentration throughout the duration of treatment. However the highest sodium concentration was observed in the group treated with 300ppm of lead for twelve weeks.

Table 4 shows the liver, kidney, spleen and brain potassium concentrations of male Wistar rats treated with graded doses of lead for a period of four, eight and twelve weeks. In the liver of rats treated with graded doses of lead there was significant (p<0.05) reduction in the liver potassium concentration compared with the control group except for eight week exposure at 200ppm where there was significant increase in the liver potassium concentration. There was significant (p<0.05) increase in the kidney potassium concentration compared with the control group, however treatment for twelve weeks at 200ppm and 400ppm, there was significant (p<0.05) increase in kidney potassium compared with the control group. In the spleen, there was significant (p<0.05) increase in the potassium concentration throughout the duration of treatment with lead, while the brain potassium concentration was significantly (p<0.05) decreased compared with the control group.

Table 4: The Mean Potassium Concentrations in Liver, Kidney, Spleen and Brain of Male Wistar Rats Treated With Graded Doses of Lead for a Period of Four, Eight and Twelve Weeks. Values are mean±SEM. Values within the same column with different superscripts are significantly different at p<0.05 Okediran B Samuel, et al. Electrolytes Alterations in Some Organs due to Lead Exposure. Adv Clin Toxicol 2019, 4(1): 000150.

Table 5 shows the liver, kidney, spleen and brain calcium concentrations of male Wistar rats treated with graded doses of lead for a period of four, eight and twelve weeks. There was significant (p<0.05) increase in the liver calcium concentration compared with the control group most especially at twelve weeks of treatment. There was significant increase (p<0.05) in the kidney calcium concentration except at four weeks of treatment with the dose of 200ppm where there was significant reduction (p<0.05) compared with the control. The spleen calcium concentration was also significantly (p<0.05) increased. There was significant reduction (p<0.05) in the brain calcium concentration at eight and twelve weeks post- exposure.

Table 5: The Mean Calcium Concentrations in Liver, Kidney, Spleen and Brain of Male Wistar Rats Treated With Graded Doses of Lead For a Period of Four, Eight and Twelve Weeks. Values are mean±SEM. Values within the same column with different superscripts are significantly different at p<0.05 Table 6 shows the liver, kidney, spleen and brain magnesium concentrations of male Wistar rats treated with graded doses of lead for a period of four, eight and twelve weeks. For four weeks treatment, there was significant reduction in the liver magnesium concentration while for twelve weeks treatment there was an increase in the liver calcium concentration compared to the control group. The kidney magnesium concentration was statistically different from the control group. There was significant reduction at eight weeks treatment compared with the control group. The spleen magnesium concentration was significantly reduced at four weeks treatment compared with the control group while the brain magnesium concentration was slightly increased at twelve weeks exposure compared with the control group.

Table 6: The Mean Magnesium Concentrations in Liver, Kidney, Spleen and Brain of Male Wistar Rats Treated with Graded Doses of Lead for a Period of Four, Eight and Twelve Weeks. Values are mean±SEM. Values within the same column with different superscripts are significantly different at p<0.05 Okediran B Samuel, et al. Electrolytes Alterations in Some Organs due to Lead Exposure. Adv Clin Toxicol 2019, 4(1): 000150.

Discussion

Lead is a ubiquitous and versatile metal which has been used by mankind for many years. It ranks as one of the most serious environmental poisons amongst the toxic heavy metals all over the world. Exposure to lead is from numerous sources and a myriad of pathways including air, food, dust, soil and water [3]. Accumulation of lead produces damaging effects in the hematopoetical, hematic, renal and gastrointestinal systems [4]. The result of this study shows accumulation of lead in the blood upon absorption, this is due to affinity of lead for red blood cells which transport them to various parts of the body and soft tissues where they are stored and results in perturbation of metabolic processes. Our results is consistent with other workers Warren, et al. [4], Murata, et al. and Okediran, et al. reported blood lead accumulation following oral exposure resulting in loss of weight, inhibition of haem synthesis and reduction of packed cell volume [16, 17].

Electrolytes plays significant role in several body processes, such as controlling fluid levels, acid-base balance (PH), nerve conduction, coagulation and muscle contraction [18]. Fluid and electrolytes homeostasis is usually maintained within narrow limits [19] and therefore, it must be kept at a level that is suitable for normal biochemical and physiological functions [20]. Therefore, imbalance in serum electrolytes is an important indicator of toxicity in identifying target organs and general health status of animals. Decrease in plasma electrolytes concentrations of sodium, potassium, calcium and magnesium was observed in this study, it is an indication in perturbation of electrolytes metabolism due to exposure to lead thus leading to alterations in cellular functions in which these electrolytes are involved. It was reported that lead can replace calcium, thereby affecting key neurotransmitters like protein kinase C, which regulates long term neural excitation and memory storage, it also affect sodium ion concentration which is responsible for numerous vital biological activities like generation of action potentials in the excitatory tissues for the purpose of cell to cell communication, uptake of neurotransmitters and regulation of uptake and retention of calcium by synaptosomes [2, 21, 22, 23].

The ionic mechanism of action for lead mainly arises due to its ability to substitute other bivalent cations such calcium, magnesium, iron and monovalent cations like sodium ions, thus affecting various fundamental biological processes of the body by damaging cellular components [24, 25]. Lead concentration in the blood is transient and only represents recent exposure of some days, as blood Okediran B Samuel, et al. Electrolytes Alterations in Some Organs due to Lead Exposure. Adv Clin Toxicol 2019, 4(1): 000150.

flows through the soft tissues, lead is deposited and bio- accumulated [26].

Exposure to lead mainly occurs through the respiratory and gastrointestinal systems. Absorbed lead is conjugated in the liver and passed to the kidney, where a small quantity is excreted in urine and the rest accumulates in various body organs. This affects many biological activities at the molecular, cellular and intercellular levels, which may result in morphological alterations that can remain even after lead level has fallen [7, 8, 9, 27].

Autopsy studies of lead exposed animals indicated that liver tissue is the largest repository of lead among soft tissues followed by kidney cortex and medulla. Lead induced hepatotoxicity was reported to be associated with the impairments of liver structure and function [28]. Environmental exposures to lead have caused nephrotoxicity in humans and animals [29]. Bio makers of kidney functions have been reported to be impaired by lead in humans and animals [30, 31, 32].

In the brain exposure of animals to lead caused impairments in hippocampus, cerebellum, cerebellar edema, cerebral satellitosis and encephalomalacia [33]. The liver is the major organ of drug metabolism and is highly exposed to both indigenous and exogenous chemical substances. Studies have shown that the liver is one of the primary targets in lead associated toxicity. Metabolism in the liver usually leads to detoxification of environmental compounds; hence the concept that the liver purifies or cleanses the blood [34]. The kidney is the major organ of drug excretion and is also one of the organs of primary target during lead toxicity. There are reports from some quarters on lead induced kidney damage in experimental animal studies and humans [35].

They brain is an essential organ of the body which is reported to be impaired on exposure to lead with respect to time. Xu, et al. [36] reported that exposure to lead before and after birth can damage short-term and long- term memory ability of young rats and hippocampal ultrastructure. The spleen plays a major role in the destruction of effete red cell thereby removing and storage of iron. The iron stored is readily released for haematopoietic.

In all these organs, ATPases play important roles in intracellular functions and for all types of physiological activities. It has been reported that inhibition of ATPases activities is used as a sensitive indicator of heavy metal toxicity in red cells, rat brain cell and rat liver cells [37, 38], while lead compound can enhance per oxidative damage to the membranes of blood cells, liver cells and other cells thus compromising cellular functions [39, 40].

In all these organs in this study, lead was reported to cause alterations in the electrolytes in these organs. It was reported that one of the potential mechanisms by which lead exhibit it toxicity is by inhibition of ATPases which is a membrane bound enzymes. It could be that inhibition of these ATPases activities which is responsible for electrolytes movement was overwhelmed and thus result in alterations of electrolytes in these organs studied. Also since membrane is made up of lipids there is every possibility that lead alters the membrane structure and could trigger lipid peroxidation thus disturbing the ATPases conformation and configuration and hence distort the electrolytes movement. Carafoli [41] reported inhibition of Ca2+-Mg2+ ATPases activities, while Guzide, et al. [42] reported inhibition of Na+-K+ ATPase and Ca2+- Mg2+ ATPases activities, transport proteins, which regulate cations flux involved in maintaining and regulating intracellular cation content by lead. Bettaiya, et al. [37] showed that lead chloride and lead acetate at micromolar concentrations significantly inhibited the Ca2+ ATPase at cellular membranes and microsomes of cerebral cortex and cerebellum in a concentration- dependent manner.

The important implication of this study is that exposure to lead is equally responsible for alteration in the electrolytes distributions in the blood as well as in organs and tissues. These alterations in these electrolytes results in impairment of physiological and metabolic activities taken place in these organs.

Our results indicate that one of the ways that lead exerts its toxic effects is disruption of electrolytes balance thus deteriorating cellular functions.