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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 35  |  Issue : 3  |  Page : 326-335

The potential combined effect of vitamins E and C on fluoride-induced hepatic toxicity in albino rats


Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Date of Submission15-Apr-2017
Date of Acceptance12-Jun-2017
Date of Web Publication07-Jan-2019

Correspondence Address:
Dr. Yassmin G Salem
Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: DOI: 10.4103/bmfj.bmfj_73_17

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  Abstract 


Background Fluoride is a well-determined nonbiodegradable and moderate pollutant, which at high levels causes serious health problems.
Aim The present study was designed to investigate the histopathological changes in liver as a result of exposure to sodium fluoride in albino rats and the possible therapeutic effect of both vitamins E and C.
Materials and methods Eighteen adult albino mice were divided into three groups (six rats per each group). The first group served as control. The second group was treated with 3.6 mg/kg body weight sodium fluoride for 30 days, and the third group received 3.6 mg/kg body weight of sodium fluoride for 30 days followed by vitamins E and C for the next 13 days. At the end of the treatment period, the animals were sacrificed by means of cervical dislocation and the liver was dissected out. Blood samples were taken for the assessment of serum glutamic-pyruvic transaminase and serum glutamic oxaloacetic transaminase.
Results Liver tissue was cleared and used for assessing the histopathological changes. Liver tissue homogenate was used for the assessment of malondialdehyde and glutathione peroxidase levels. The histopathological results in the present study indicated that exposure to sodium fluoride for 30 days caused degenerative changes in the liver. Light microscopic examination revealed the degenerative changes in the liver, such as disorganization of the cell plates, dilation of the central vein, pyknotic nucleus, ballooned hepatocytes and hepatocytes with empty nuclei, and disturbed mucopolysaccharide metabolism in liver cells. Biochemical examination revealed elevated serum glutamic-pyruvic transaminase, serum glutamic oxaloacetic transaminase, and malondialdehyde and decreased glutathione peroxidase level.
Conclusion Administration of vitamins E and C during the first 13 days of the recovery period of sodium fluoride intoxication revealed minimal improvement, which was detected at the biochemical and metabolic level.

Keywords: sodium fluoride, vitamin C, vitamin E


How to cite this article:
El Din AM, Sherif RN, El Khyat SM, Salem YG. The potential combined effect of vitamins E and C on fluoride-induced hepatic toxicity in albino rats. Benha Med J 2018;35:326-35

How to cite this URL:
El Din AM, Sherif RN, El Khyat SM, Salem YG. The potential combined effect of vitamins E and C on fluoride-induced hepatic toxicity in albino rats. Benha Med J [serial online] 2018 [cited 2019 Dec 15];35:326-35. Available from: http://www.bmfj.eg.net/text.asp?2018/35/3/326/249429




  Introduction Top


The liver represents the main detoxifying tissue, which acts by processing, neutralizing, and getting rid of toxins from the digestive tract through hepatocyte-mediated enzymatic detoxification systems [1].

It was identified that evidence of changes in the liver due to toxicants has been revealed by abnormal metabolic functions, reduced activity of detoxification reaction, and altered structure of subcellular organelles [2].

Fluoridated toothpastes, fluoride-containing mouthwash, fluoride tablets, and topical gels are broadly used dental products in which fluoride contributes in its structure. As mentioned, it is very important to keep continual low levels of its ions in the oral media to prevent dental caries and to promote the remineralization of enamel [3].

Fluoride contributes in some general anesthetic drug structure such as sevoflurane, desflurane, and isoflurane. Moreover, there are fluorinated anti-inflammatory dexamethasone and triamcinolone. Furthermore, it contributes in selective serotonin reuptake inhibitors and antidepressants such as citalopram, escitalopram oxalate, fluoxetine, fluvoxamine maleate, and paroxetine, which are fluorinated molecules [4],[5]. It was highlighted that fluorouracil is considered as a major therapeutic approach and the standard first-line treatment for colorectal cancer [6].

Vitamins C and E are capable of scavenging free radicals and retarding reactive oxygen species-provoked cellular damage [7]. Actually, vitamin E, especially the α-tocopherol, is the principal peroxyl radical scavenger in the biological lipid phases, such as membranes. Furthermore, vitamin C has the capability to get rid of free radicals directly in the aqueous phases of cells and vascular system. It can also guard membranes and other hydrophobic compartments from deleterious damage by recycling the antioxidant form of vitamin E [8].


  Aim Top


The study was designed to assess the pathomorphological changes in albino rat liver exposed to sodium fluoride in drinking water and to assess the potential therapeutic effect of vitamins C and E on fluoride toxicity during the recovery period.


  Materials and methods Top


Animal model

Eighteen adult albino rats with no respect to sex, weighting 150–250 g, were obtained from Mansoura Experimental Research Center, Egypt. They were housed in stainless steel mesh cages under control condition of temperature (23±3°C), and relative humidity throughout acclimatization and experimental periods, with ad libitum access to food and water and fixed 12 : 12-h light/dark cycle. All rats were maintained under specific pathogen-free conditions in the animal house. All experiments were carried out according to the rules and regulations laid down by the Committee on Animals’ experimentation of Mansoura University.

Chemicals

  1. Sodium fluoride, vitamin C (ascorbic acid), and vitamin E (α-tocopherol) were purchased from Sigma-Aldrich (Cairo, Egypt).
  2. Sodium fluoride and vitamin C were given to rats orally in 10 ml distilled water using stomach tube.
  3. Vitamin E was given intraperitoneally dissolved in olive oil.


Experimental design

The albino rats were divided into three groups; one served as the control group and two were the experimental groups. Each consisted of six rats:
  1. Control group.
  2. Group II (the fluoride-treated group) received aqueous solution of sodium fluoride at a dose of 32 mg/l corresponding to the dose of 3.6 mg fluoride/kg body weight for 4 weeks.
  3. Group III (fluoride then vitamin-treated groups) received aqueous solution of sodium fluoride at a dose of 32 mg/l for 4 weeks followed by vitamin E 250 mg/kg body weight daily through intraperitoneal route in addition to vitamin C 20 mg/kg body weight daily orally for the next 4 weeks.


Specimen collection

Specimens were collected at the assigned time (30 days for the first and second groups and 60 days for the third group) (six rats from each group). The rats were sacrificed by means of cervical dislocation. Blood samples were collected by means of direct cardiac puncture into sterilized and heparinized syringes and were used to estimate serum glutamic-pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT). The liver was dissected, divided, and processed for light microscopic examination. Another portion of the liver was homogenized for quantitative analysis of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in tissue homogenate.

Estimation of serum alanine transaminase and aspartate transaminase

The serum samples were obtained by means of blood centrifugation for 10 min at 5000g at 4°C as previously described by Jia et al. [9]. The levels of serum SGPT and SGOT were assayed according to the routine biochemical analysis system using clinical test kits spectrophotometrically (Elitech, London, UK) [9].

Assessment of lipid peroxidation and oxidative stress

Portions of livers were homogenized (10% weight/volume) in ice cold 0.1 mol/l tris-HCl buffer (pH=7.4). The homogenate was centrifuged at 3000 rpm for 10 min at 4°C. Oxidative stress markers were detected in the resultant supernatant of liver homogenate as previously described by Jia et al. [9]. The appropriate kits (Biodiagnostics, Giza, Egypt) were used for the determination of reduced GSH-Px and lipid peroxidation, which was measured by the formation of MDA.

Processing of the specimens for light microscopic examination

The specimens were processed for paraffin sectioning by gradual dehydration using ascending graded concentrations of alcohol, cleared in xylene, and embedded in soft followed by hard paraffin wax. Sections were of 5–6 μm thickness were prepared using microtome and mounted on the slide for staining according to Bisen [10]. The tissues were stained with hematoxylin and eosin (H&E) and periodic acid–Schiff (PAS) as described by Bancroft and Layton [11].

Statistical analysis

Serum alanine transaminase and aspartate transaminase, liver MDA, and GSH-Px were all presented as mean and SD, and the mean of two groups were compared using Student’s t-test. Statistical analysis was carried out using SPSS program (version 22, IBM, New York, New York, USA). A P-value of less than 0.05 was considered significant.


  Results Top


Biochemical results of study groups

Control group

  1. Assessment of liver functions:

    The SGPT and SGOT were within normal range in all rats of the control group.

    The serum level of SGPT was 27.43±2.26 U/l and that of SGOT was 88.57±6.85 U/l (Tables 1 and 2).
    Table 1 Statistical comparison of serum glutamic-pyruvic transaminase levels among different groups

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    Table 2 Statistical comparison of serum glutamic oxaloacetic transaminase levels among different groups

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  2. Assessment of MDA and GSH-Px in liver tissue:

    The levels of MDA and GSH-Px in liver tissue of all control rats were within normal range. The level of MDA in liver tissue was 1.44±0.11 nmol/ml and the level of GSH-Px in liver tissue was 1.58±0.05 nmol/ml tissue (Tables 3 and 4).
    Table 3 Statistical comparison of malondialdehyde levels in liver tissue among different groups

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    Table 4 Statistical comparison of glutathione peroxidase levels in liver tissue among different groups

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Fluoride-treated group

  1. Assessment of liver functions:

    The animals that received sodium fluoride orally for 4 weeks showed elevation in serum levels of SGPT and SGOT. The serum level of SGPT and SGOT were 47.71±3.45 and 177.14±22.06 U/l, respectively. These levels were significantly high as compared with the control value (Tables 1 and 2).

  2. Assessment of MDA and GSH-Px in liver tissue:

    There was a significant increase in lipid peroxidation in the liver of the animals that received sodium fluoride orally for 4 weeks. The level of MDA in liver tissue was 2.84±0.25 nmol/ml tissue. This value was significantly high as compared with the control group, whereas the level of GSH-Px in liver tissue of same group was 0.98±0.05 nmol/ml tissue, which was significantly low as compared with the control value (Tables 3 and 4).


Fluoride followed by vitamins E and C-treated group

  1. Assessment of liver functions:

    Serum level of SGPT and SGOT after daily administration of sodium fluoride for 4 weeks followed by administration of vitamins E and C for the next 4 weeks resulted in a decrease in serum enzymes as compared with the fluoride group but still significantly high versus the control group. SGPT and SGOT were 38.86±4.53 and 126.43±9.41, respectively(Tables 1 and 2).
  2. Assessment of MDA and GSH-Px in liver tissue:

    There was a significant decrease in MDA level (2.35±0.31 nmol/ml tissue) and an increase in the level of GSH-Px (1.13±0.12 nmol/ml tissue) after daily administration of vitamins E and C for 4 weeks after stoppage of fluoride administration as compared to the animals that received fluoride only (Tables 3 and 4).


Light microscopic examination

Hematoxylin and eosin-stained sections

Control group.

The liver of thecontrolrat consisted of the classical hepatic lobules with central hepatic venules. The lobules were formed of cords of hepatocytes forming flat, anastomosing plates radiating from the central vein and separated by hepatic sinusoids ([Figure 1] and [Figure 2]).
Figure 1 A photomicrograph of a liver section from control rat showing hepatic cords radiating from the central vein (Cv). The hepatic cords are separated by the hepatic sinusoids (small arrows), which are lined with endothelial cells and Kupffer cells (K) showing normal portal tract (large arrow) containing bile ductule (B) lined by cuboidal epithelium and branch of portal vein (pv). Hematoxylin and eosin, ×100

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Figure 2 A photomicrograph of a liver section from control rat showing normal hepatocytes (H) exhibiting abundant eosinophilic cytoplasm and large central open face nuclei, uniform in size, and with normal euchromatin (small arrow). Binucleated hepatocytes are also seen (large arrows). Hepatocyte cords are separated by blood sinusoids (BS) containing Kupffer cells (K). This is a portal tract containing (B) Bile ductile, (A) hepatic artery branch, (PV) portal vein radicle. Hematoxylin and eosin, ×400

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The cytoplasm of the hepatocytes was generally eosinophilic. They had one or two central spherical or ovoid vesicular nuclei with one or two prominent nucleoli and peripherally dispersed chromatin ([Figure 2]).

The hepatic sinusoids were lined with endothelial cells with flat darkly stained nuclei and Kupffer cells with elongated nuclei ([Figure 2]).

At the corners of lobules, there were portal tracts that consisted of connective tissue containing small artery, vein, and a small bile duct ([Figure 2]).

Fluoride-treated group.

H&E-stained sections of the liver of rats treated with sodium fluoride showed loss of normal hepatocytes architecture, dilated central vein, with perivenular inflammatory cell infiltration, and necrosis ([Figure 3],[Figure 4],[Figure 5]). The hepatic sinusoids appeared congested and dilated ([Figure 6]). Some hepatocytes showed swollen cytoplasm with feathery (hydropic) degeneration, whereas others showed marked vacuolation and fatty degeneration (macrovesicular and microvesicular steatosis) ([Figure 3],[Figure 4],[Figure 5],[Figure 6]). The nuclear injury observed in the present work was characterized by the presence of pleomorphic nuclei, where some nuclei appeared swollen and large and other nuclei appeared small ([Figure 4] and [Figure 5]). In addition, peripheral chromatin clumping was evident among some hepatocytes ([Figure 5]). However, some hepatocytes revealed necrotic changes including pyknotic nuclei and others were empty; devoid of nuclei ([Figure 4] and [Figure 5]).
Figure 3 A photomicrograph of a section of the liver of the fluoride-treated group (group II) showing macrovesicular steatosis (black arrows). Most of the hepatocytes show evidence of hydropic degeneration (blue arrows) with palely stained cytoplasm and darkly stained nuclei; mononuclear inflammatory cellular infiltration could be seen around the central vein (cv) and bile ductules (BD) (white arrows). Hematoxylin and eosin, ×100

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Figure 4 A photomicrograph of a section of the liver of the fluoride-treated group (group II) showing dilatation of the central vein (cv) with centilobular necrosis, mononuclear inflammatory cellular infiltration around the central vein (white arrow). Nuclei of hepatocytes are variable in size (1, 2) and some hepatocytes with pyknotic nuclei (black arrows) and macrovesicular steatosis (red arrows) could be seen. Hematoxylin and eosin, ×400

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Figure 5 A photomicrograph of a section of the liver of the fluoride-treated group (group II) showing ballooning of hepatocytes with vacuolated cytoplasm; some hepatocytes are empty without nucleus (blue arrows). Nuclei of hepatocytes are variable in size (1, 2) and show abnormal appearance with peripheral heterochromatin (black arrows) and mononuclear Inflammatory cellular infiltration around central vein (cv) (red arrow). Hematoxylin and eosin, ×400

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Figure 6 A photomicrograph of a section of the liver of the fluoride-treated group (group II) showing macrovesicular steatosis of hepatocytes; the cytoplasm of the hepatocytes have multiple large fat vacuoles (blue arrows); dilated blood sinusoids can be also seen(black arrows) with mononuclear inflammatory cellular infilteration (red arrow). Hematoxylin and eosin, ×400

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Fluoride followed by vitamins E and C-treated group

H&E-stained sections of fluoride followed by the vitamins E and C-treated group revealed manifestations of hepatic damage. Most of the hepatocytes showed evidence of hydropic degeneration with palely stained cytoplasm and darkly stained nuclei, and mononuclear inflammatory cellular infiltration around the central vein ([Figure 7],[Figure 8],[Figure 9]); some hepatocytes were empty without nucleus ([Figure 8]). Nuclei of hepatocytes were pleomorphic, variable in size; other hepatocytes showed pyknotic nuclei ([Figure 8] and [Figure 9]) and macrovesicular steatosis of hepatocytes ([Figure 7],[Figure 8],[Figure 9]); dilated central vein could be also seen ([Figure 8]).
Figure 7 A photomicrograph of a section of the liver of the fluoride then vitamins E and C-treated group (group III) showing macrovesicular steatosis (black arrows). Most of the hepatocytes show evidence of hydropic degeneration (blue arrows) with vacuolated cytoplasm and darkly stained nuclei pericentral necrosis with mononuclear inflammatory cellular infiltration around the central vein (cv) (white arrows). Areas of necrosis could be seen (large blue arrows). Hematoxylin and eosin, ×100

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Figure 8 A photomicrograph of a section of the liver of the fluoride then vitamins E and C-treated group (group III) showing ballooning of hepatocytes with vacuolated cytoplasm (blue arrows); some hepatocytes are empty without nucleus (red arrows). Nuclei of hepatocytes are variable in size (1, 2) and macrovesicular steatosis of hepatocytes is observed (black arrows); dilated central vein (cv) can be also seen, inflammatory cellular infiltration around it (orange arrows). Hematoxylin and eosin, ×400

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Figure 9 A photomicrograph of a section of the liver of the fluoride then vitamins E and C-treated group (group III) showing ballooning of hepatocytes, nuclei of most hepatocytes are small pyknotic (blue arrows) and areas of necrosis with mononuclear inflammatory cellular infiltrate around dilated central vein (cv) (black arrows); macrovesicular steatosis could be also seen (red arrows). Hematoxylin and eosin, ×400

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Periodic acid–Schiff stained sections

Control group.

Hepatocytes of the liver of control rat showed strong PAS-positive reaction ([Figure 9]).

Fluoride-treated group.

Fluoride-treated rat liver for 4 weeks induced weak positive PAS reaction ([Figure 10]).
Figure 10 A photomicrograph of liver section of control rat showing strong periodic acid–Schiff-positive reaction observed in hepatocytes. Note that the peripheral zonal cells (blue arrows) have higher mucopolysaccharide content compared with central zonal cells (black arrows). Periodic acid–Schiff, ×100

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Fluoride then vitamins E and C-treated group

Daily administration of vitamins E and C immediately after fluoride intoxication induced moderate positive PAS reaction (contro PAS, [Figure 10]; Fluoride PAS, [Figure 11]; Fluoride then vitamins PAS, [Figure 12]).
Figure 11 A photomicrograph of a section of the liver of the fluoride-treated group (group II) showing weak periodic acid–Schiff reaction of hepatocytes. Periodic acid–Schiff, ×100

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Figure 12 A photomicrograph of a section of the liver of the fluoride then vitamins E and C-treated group (group IV) showing moderate periodic acid–Schiff-positive reaction of hepatocytes. Periodic acid–Schiff, ×100

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  Discussion Top


In the study, sodium fluoride was used at a dose of 32 mg/l corresponding to a dose of 3.6 mg/kg body weight for 4 weeks. This dose was previously used by Dąbrowska et al. [1] to assess sodium fluoride toxicity.

Results of the present study confirmed implication of sodium fluoride toxicity and clarified the possible therapeutic effect of coadministration vitamins E and C on the structure of the liver.

As the liver carries out the metabolism of toxic compounds produced during systemic transformations and exogenous toxins getting into the organism from the environment, we could expect to detect both metabolic and pathomorphological changes as reactions to sodium fluoride [12].

Cell respiration disorders can interfere with reduction and oxidation mechanisms through impairment of protein, carbohydrate, and lipid metabolism and through intracellular and extracellular transport disturbances. This is considered the main hepatotoxic action of sodium fluoride. Subsequently, damage of the whole cell or its cytoplasmic organelles can occur. Vacuolar ballooning degeneration, necrosis of hepatocytes, or disturbances in the metabolic enzymes activity are the most frequently observed damage in previous studies [13].

Biochemical examination of the fluoride-treated group showed significantly elevated liver enzymes (SGOT and SGPT) in serum, significantly elevated MDA, and decreased GSH-Px in liver tissue. These results are in agreement with Zhang et al. [14].

Lipid peroxidation is one of the major characteristics that can be included as an oxidative stress marker [15]. Our results showed that sodium fluoride increases lipid peroxidation with a significant increase in the level of MDA in liver tissue as a main product of lipid breakdown. These results are in accordance with many reports that found an increase in the level of MDA in tamoxifen-intoxicated rats, as highlighted by Al-Jassabi et al. [16].

Our results showed that fluoride resulted in a significant decrease in GSH-Px, which contributes to antioxidant activities. This decrease in GSH-Px level was explained by Park et al. [17], who stated that fluoride cause alternation in lipid profile, which is accompanied by elevations in reactive oxygen species formation and reduction in antioxidant activities, including SOD and GSH-Px.

H&E-stained sections of the liver from rats of the sodium fluoride-treated group for 4 weeks showed necrotic foci, marked disrupted hepatic cords, inflammatory cell infiltration, and degenerative changes such as pleomorphic nuclei, pyknotic nuclei, hydropic, and fatty degeneration. These results are in agreement with correlating study results [18],[19].

Vacuolation revealed in the pathology of present study may be attributed to outer mitochondrial membrane extension [20]. Ionic disturbance of the cell which in turn results in sodium plus water retention, which consequently leads to cellular ballooning, might be another explanation to the detected vacuolation [21],[22].

Fatty changes concealed in the liver may be attributed to that there is defective protein synthesis and lipoprotein structure, which is involved in the transfer process of hepatic triglycerides to circulation. As a consequence, accumulation of lipid globules in the cytoplasm occurs [23].

It was previously demonstrated by Western blotting analysis that apolipoprotein E, which is concerned with lipid transport, was downmodulated and glucose-regulated protein-78, which is concerned with antioxidative stress functions, and was upregulated in the liver in response to fluoride and concluded that fluoride can cause disturbances in lipid and carbohydrate metabolism [24].

It was verified in the current work that oral fluoride intake contributes in pathomorphological changes shown in albino rat liver. This is attributed to the occurrence of lipid peroxidation and accumulation of free radicals within hepatic cells [1].

It was asserted that apoptosis has critical association to oxidation, which was confirmed by pyknosis of some nuclei [25].

According to the present study, the bile canaliculi revealed some changes marked by slight dilatation of their lumina; such changes have probably occurred as a result of excretion of a part of fluoride in bile causing devastation of the bile canaliculus as believed by some authors in other cases of drug treatments [26],[27].

PAS-stained sections of the fluoride-treated group showed weak PAS-positive reaction. This weak PAS-positive reaction was caused by marked diminution in mucopolysaccharides content of hepatocytes. Outcome of the current work is parallel to Kukiekka [28], who stated that smooth endoplasmic reticulum can also be subjected to vacuolization, which in turn leads to considerable decrease in the count of glycogen granules in the affected sites. This result also was in agreement with Dąbrowska et al. [1].

Glycogen decrement concealed in the current study may also be illustrated by that this depletion occurred most likely as a consequence to both hydropic and fatty degeneration revealed in the current work, or due to the ruining effect of drug agent on the organelles and the related enzymatic system [29].

The most important mechanism of fluoride hepatic injury is that sodium fluoride accelerates the cycle of apoptosis within cells. The PI3K-Akt signal pathway was identified to have a significant role in the promotion of cell growth and inhibition of apoptosis of cells [30],[31]. It is indicated that abnormal changes in the PI3K-Akt signal pathway and intracellular calcium-ion may have relationship with the tissues injury in the fluorosis [32].

As regards the vitamins, mechanism of action is that when vitamin E intercepts a radical thus forming a complex α-tocopheroxyl radical, which can be reduced back to α-tocopherol by vitamin C or other reducing agents, thus attenuating the propagation of free radical reactions [33]. Thus, pro-oxidant activity of vitamin E could be prevented by vitamin C by decreasing the activity of tocopheroxyl radical to α-tocopherol, which in turn contributes to the increase in the total antioxidant status and reduction in oxidative stress [34].

In the present study, administration of vitamins E and C immediately after withdrawal of fluoride revealed some improvement in liver function as there were still elevated liver enzymes (SGOT and SGPT) in serum, elevated MDA and decreased GSH-Px in liver tissue but with some improvement compared with the fluoride group.

Light microscopic examination of the liver showed no significant improvement in hepatocyte architecture but there was moderate positive PAS reaction.

Unlike our results as regards the fluoride then vitamins group, it was previously revealed that ascorbic acid (vitamin C) and vitamin E administration for 30 days are capable of completely, or almost completely, mitigating liver fluoride toxicity in mice induced by fluoride during the recovery period. It was assessed that there was reversal of most of the hepatic biochemical parameters during the first 30 days of recovery period [35]. This may be attributed to the fact that mice liver cells may reveal more rapid response to vitamins compared with the rat liver cells.

Our results as regards the fluoride then vitamins treated group were also contradictory to Gallo et al. [36], who assessed the therapeutic effects of vitamins E and C on placental oxidative stress induced by nicotine.

Although there was minimal improvement and improved PAS reaction, which was moderately positive as compared with fluoride group, which was a weak reaction, it may denote its transitory nature. This is confirmed by a previous study [1].

In conclusion, fluoride treatment for 13 days induced significant histological, biochemical, and metabolic changes in albino rat liver. Administration of vitamins E and C during the first 13 days of the recovery period of sodium fluoride intoxication revealed minimal improvement. Therefore, it may need longer duration for remission or need more dose of vitamins to ameliorate fluoride toxicity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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