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BCH00029 - EFFECT OF FLORIDE INTOXICATION IN LIVER OF MALE WISTAR ALBINO RATS


ABSTRACT

 

Flurosis disease is a dreaded caused due to high fluoride (>1.5 ppm) in drinking water. The aim of this review is to highlight on intoxication of fluoride on liver of wistar rat which are expose to Subacute doses of NaF. In the present study normal male rats, weighing between 150- 200 gm, were kept on subacute dose of sodium fluoride (10ppm, 20ppm, 40ppm) through drinking water for 30 days. The results revealed that, enzyme activity of glutathione s transferase, significantly decrease in 10ppm when compared to that of control, while that of 20ppm and 40ppm increase respectively. Also, enzyme activity of glutathione peroxidase increases throughout the whole group when compared to the control. Catalase activity decrease in 10ppm but increases in 20ppm and 40ppm respectively when compared to the control. For reduced glutathione activity there was significant decrease in 10ppm, 20ppm, while that of 40ppm increase than the other group when compared to the control group, This review shows fluoride toxicosis caused an elevation in the enzyme activities of glutathione s transferase (GST), glutathione peroxidase (GPx), reduced glutathione (GSH). Treatment of experimental animals with NaF induced oxidative stress in hepatic tissues. It can be concluded that administration of sodium fluoride to experimental animals induced oxidative stress, serious hepatic disease, and distur-bance in liver functions. So, human should be advised to decrease exposure to sodium fluoride to decrease the harmful effects of NaF on liver.

CHAPTER ONE

1.0       INTRODUCTION

1.1       BACKGROUND OF STUDY

 Fluoride anions are present in water sources, ground water and drinking water as they are released from the run of fluoride- containing rocks and soils and filtered into water, thus the consumption of such water is typically instrumental to daily fluoride in take (NRC, 2006). Inorganic fluorine is used in aluminium production and as a flux in the steel, glass fiber industries and wood preservatives (Mueller, 2001), besides, it is commonly used in pesticides, fungicides and insecticides, various types of adhesives, glues and as a preservative (Budavari, 1989). Sodium fluoride compounds are used in the form of fluorinated water, tooth paste, mouth washes and fluoride tablets for prevention of dental caries (Dabrowaka et al., 2006), therefore, the exposure of populations to fluoride compounds has become significant (ATSDR, 2014). ten Cte, (2013) reported that fluoride reduces the decay of teeth enamel via reduce the rate of tooth enamel demineralization and an increase in the rate of remineralization of teeth. Anjum et al., revealed that the fluoride caused impairment liver function, causing decrease in metabolic activities such as glycolysis, oxidative phosphorylation and lipid peroxidation, increased serum indices of liver function tests, inhibit certain antioxidant enzymes and molecules (Abdel Wahab, 2013). It also increase intracellular levels of the superoxide radical disturbed of lipid profile (Hassan, 2009). Hens treated with sodium fluoride in ration showed mild or severe enlargement of their liver (Mohammed et al., 2012). Some studies have shown that exposure to sodium fluoride caused a reduction in the protein content in the serum and liver (Jha et al.,). Domestic animals consumption contaminated food and water with superphosphate fertilizer were suffering from signs of dental discoloration, difficulty in mastication and weakness (Patra et al., 2000). 

1.1.0    Toxin

            Toxin can be a substance, small molecules, peptide, or proteins that are capable of causing disease on contact with or absorption by body tisuses interacting with biological macromolecules such as enzymes or cellular receptors (Kishi et al.,2001).

 

Toxicant is used to denote substances made by human or introduced by humans or into the environment by human activities.

 

1.1.1    Aim and Objective of the Research

            This research aims towards investigating the effect of fluoride intoxication on the liver and its effects using antioxidant enzymes:

  • Glutathione S Transferase level in male albino whister rats.
  • Glutathione peroxidase level in male albino whister rats.
  • Reduced Glutathione level in male albino whister rats.
  • Catalase Activity in male albino whister rats.

 

 

 

 

 

 

 

 

 

 

1.2    LITERATURE REVIEW

1.2.1    Flouride

            In the halides group of the periodic table, fluoride (F) has great importancy due to its smallest size and most electronegativity. Although the mechanisms of F in biological forms are remains unclear but it has the unique chemical and biochemical properties for the size and reactivity (Jentsch et al., 2002). It is ubiquitously present in soil, water, plants and air. In the animal body, F makes its presence through water and food. But, some of the recent studies indicate that, most of the F comes from pharmaceutical drugs (20%) and through agrochemicals (30- 40%) (Nabavi, 2012). The variability and presence of fluoride depends upon the location. It was found that F is present in the soil within the range of 10-1000 parts per million (ppm). However, in water it ranges from 0.5 to 2000 ppm. This incident depends upon the sources of water (Weinstein, 2004). According to World Health Organization (WHO), F exposure to animals above the 1.5 ppm, set at chronic fluoride toxicity. Through water exposure, this type of toxicity is going to endemic in most of the countries across the world (WHO, 2003) In USA, the normal level of F in drinking water is 4 mg/L (USEPA 2003). But, in the European country, it is 0.8ppm (EC 2011). In India, most of the states are showing the greater level of F in drinking water (PC 2007). Fluoride exerts its effects on plants also (Alves, 2008), It attenuates all the cells and tissues, impaired the stomatal conductance. Simultaneously, it acts as the metabolic and reproductive inhibitor, impaired photosynthesis and respiration pathways. Ultimately, F caused even to plants death (Khandare, 2007). In animals, fluoride intoxication causing skeletal impairment, called as skeletal fluorosis.

Recently, high fluoride intake has been associated with dental cancer and tumors of other organs. First clinical symptoms appeared like reduced in food intake and loss of body weight gain. After attenuating the antioxidant defence mechanism, F also affect to the gastrointestinal tract, brain, muscle etc. In the halides group of the periodic table, fluoride (F) has great importancy due to its smallest size and most electronegativity.                                             Although the mechanisms of F in biological forms are remains unclear but it has the unique chemical and biochemical properties for the size and reactivity. It is ubiquitously present in soil, water, plants and air. In the animal body, F makes its presence through water and food. But, some of the recent studies indicate that, most of the F comes from pharmaceutical drugs (20%) and through agrochemicals (30-40%). The variability and presence of fluoride depend upon the location. It was found that F is present in the soil within the range of 10-1000 parts per million (ppm).                                               

However, in water it ranges from 0.5 to 2000 ppm. This incident depends upon the sources of water. According to World Health Organization (WHO), F exposure to animals above the 1.5 ppm, set at chronic fluoride toxicity. Through water exposure, this type of toxicity is going to endemic in most of the countries across the world. In USA, the normal level of F in drinking water is 4 mg/L. But, in the European country, it is 0.8ppm. In India, most of the states are showing the greater level of F in drinking water. Fluoride exerts its effects on plants also It attenuates all the cells and tissues, impaired the stomatal conductance. Simultaneously, it acts as the metabolic and reproductive inhibitor, impaired photosynthesis and respiration pathways. Ultimately, F caused even to plants death. In animals, fluoride intoxication causing skeletal impairment, called as skeletal fluorosis.                                                               

Recently, high fluoride intake has been associated with dental cancer and tumors of other organs. First clinical symptoms appeared like reduced in food intake and loss of body weight gain. After attenuating the antioxidant defence mechanism, F also affect to the gastrointestinal tract, brain, liver and muscle etc.

1.2.2    Chemistry of fluoride

            Fluorine holds the 13th rank among the elements (Adriano 1986; Krauskopf and Bird 1995) in its abundance in the earth. It is accounted as an incompatible lithophilic element (Faure 1991) and the most electronegative. Fluoride ion, as a strong ligand in water, forms a number of soluble complexes with polyvalent metal ions such as Mg2+, Fe3+, Al3+, and Ca2+ based on the pH of the medium (Nordstrom and Jenne 1977). It can also form hydroxide complexes with boron as [BFn(OH)4 − n]−, silica complexes (SiF4 and SiF62−), and other strong complexes with beryllium, uranium, vanadium, and REEs (Serrano et al. 2000). Fluorine (F) is the most reactive nonmetal and the most electronegative element, and therefore almost never occurs in nature in its elemental state; it combines with all elements, except oxygen and the noble gases, to form fluorides. Sodium fluoride appears as an odourless white powder or colourless crystals, with a water solubility of 4% at 15C and a pH (saturated solution) of 7.4 (Budvari,  Merck, 1989).

 Hydrogen fluoride or hydrofluoric acid is a colourless gas or fuming liquid with strong irritating odour, highly corrosive, very soluble in water and with a vapour pressure of more than 1 atmosphere. Odour detectable limits are 0.033–0.1333 mg/m3, while the irritating concentration is 4.17 mg/m3, (Ruth, 1986).

1.2.3    Sources of fluoride

            Natural and anthropogenic sources are the two main ways through which F entered in the environment (Cengeloglu, 2002).

 

Natural sources

Soil:

            The normal total fluoride content of soil ranges from 150-400 mg/kg. F level in the clay soil is 1000 mg/kg (Susheela 1999). Contamination to soil is because of the utilization of phosphorus fertilizers which have total 1-1.5% fluorine (Bombik, 2011).Contaminated soil with F, show it’s toxicity after the inhalation of soil contaminants which have been vapourized or through the contaminated ground water after the F leaching from the soil (Begum,2012).

Water:

            Water containing the F concentration up to 1.0 mg/L is safe. Whereas, the F levels in between 1.1 and 2.5 mg/L are marginally contaminated. However, above 2.6 mg/L F level is determined as the highly contaminated (Susheela, 1999). It was found that the level of F in ground water is higher than the surface water as the F percolates from the soil to ground water through leaching process. There are several factors which are responsible for the presence of F in natural ground water from the soil. Among them, geological factors, consistency of the soil, nature of rocks, pH and temperature of the soil, chelating action of other elements, depth of wells, leakage of shallow groundwater, and chemical and physical characteristics of water (Wang et al., 2014). Water is an important source of F exposure to human beings and animals

Forage, grasses and grains:

            At the vicinity of industrialized area, it was found that forages and grasses contain the higher level of F than the other area. Some studies also found that, grasses and forages has the higher level of F than the industrialized area. It is due to the fluoride rich dust, ash, raining factors for which plants could be affected far from the industry. Plants contamination depends upon several factors like the amount of F released in to the atmosphere, distance between the F source and contaminated area, type of vegetation, height of plants, atmospheric condition, and seasons etc. (Radostits, et al.,). It has been established the relationship between the F level in soil and plants of F will be increased by 3 ppm for each 100 ppm increase in soil F up to the 2200 ppm (Mascola, 1974).

Volcanic activities:

            Due to volcanic eruption, animals and plants kingdom have been affected throughout the globe. Volcanic ash contains high level of F and contaminations of F to the geochemical cycle are frequent. From the volcanic eruption, F has been released in the form of hydrogen fluoride. Erupted F may covered several places and stay for many years. After decaying and leaching, F caused severe casualty to domestic and wild animals (Bellomo, 2007)

Anthropogenic sources

            Anthropogenic fluoride contamination happens by human activities like industrialization, motorization, fluoride containing pesticides, fluoridation of drinking water supplies, dental products, refrigerants, and fire extinguishers (WHO, 2002). F contamination due to airborne sources also occurred. The mean F concentration in normal areas (unpolluted/nonindustrialized) is generally less than 0.1μg/m3. The levels may be slightly higher in the vicinity of industries, but should not exceed 2–3μg/m3 (Weinstein, Davison 2004).

In many countries, coal burning for household purposes was documented as the main source of F causing endemic fluorosis (WHO, 2000). Industrial release fluoride rich fumes and effluents into the environment also caused casualty in livestock sector like cattle, buffaloes, sheep, goats, camels etc. (Karram, Ibrahim 1992). There are several reports documenting mineral mixture supplements as a major source of fluoride toxicity in livestock (Singh, Swarup 1995). Moreover, incorporation of modern creation and utilization of chemicals in different sectors like hydrogen fluoride (HF), calcium fluoride (CaF), sodium fluoride(NaF), fluorosilicic corrosive (H SiF), sodium hexafluorosilicate (Na SiF), sulfur hexafluoride (SF), and phosphate manures are the main sources of fluoride.