Open access peer-reviewed chapter

Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawi

Written By

Sihem Mbarek, Tounes Saidi and Rafika Ben Chaouacha-Chekir

Submitted: November 30th, 2011 Reviewed: June 4th, 2012 Published: September 19th, 2012

DOI: 10.5772/50421

Chapter metrics overview

2,076 Chapter Downloads

View Full Metrics

1. Introduction

Body fluid regulation is highly diverse among different animals according to their phylogenic position and the ecological condition [1]. The maintenance of water homeostasis in arid and semi-arid rodent habitats is a critical body function to survive the continually changing environmental condition. The combined effects of anatomical adaptations, behavioural patterns and interactions between hormonal systems allow these small mammals to minimize energetic costs and to finely balance body fluids under a wide range of conditions [2-3]. This is made possible essentially, by homeostatic mechanisms that concentrate urine as an indicator of water regulation efficiency as well as an advantage for colonization and survival [4].

Meriones shawi(Muridae) a semi-desert rodent found in the coastal zone of North-west Africa from Morocco to Egypt [5],has a particular ability to support water restrictionuntil several months [6]. It appears thatwater intake and water loss are finely balanced by Meriones shawi. Water intake was provided from preformed water of food and by metabolic water production as described by King and Bradshaw[7].Water loss was limited by the production of very dry feces. In addition, Meriones shawiproduces concentrated urines as results of high plasma concentrations of arginine-vaspressin (AVP) and a large capacity of increasing hypothalamic AVP synthesis and hypophyseal storage [8]. The mean value to concentrate urine in the Meriones shawisubmitted to water dehydration during 10 days, increased from 1500 mOsm Kg-1H20/ to 3000 mOsm.Kg-1 H20 under laboratory conditions. The maximal capacity to concentrate urine (recorded under laboratory conditions) ranged from approximately 4500 mOsm Kg-1 H20 in the Meriones shawi[9]. The alterations of kidney Na-K-ATPase activity, including pronounced heterogeneity of ATPase distributions in nephrons and increased Na-K-ATPase activity in the medullary limb, observed in response to water restriction, can be responsible for this ability [10]. However, AVP is the most important hormone to elaborate urines largely hyperosmotic to plasma. A comparative study of water controlling behavior was done between rat laboratory and Meriones shawidemonstrated that the level of AVP is 4-fold greater than in dehydrated rats [11]. AVP levels are highly dependent on the state of hydration and correlate with urinary osmolality [12].

AVP or antidiuretic hormone (ADH), is known to be primarily involved in water absorption in the distal nephron of the kidney in mammals. This peptide is synthesized in the soma of hypothalamic magnocellular neurosecretory cells (MNCSs) located in supraoptic (SON) and paraventricular (PVN) nuclei. After water deprivation the axons MNCs project to the neurohypophysis, where Ca2+ dependent exocytosis in their nerve terminals causes the release of AVP in blood circulation. The small peptide is secreted by the neurohypophysis in response to increases in plasma osmolality. AVP effects on the renal tubule are mediated by hormone binding to V2 type basolateral receptors coupled trough Gs to adenylyl cyclase and activation of the cyclic adenosine monophosphate - Protein kinase A (cAMP-PKA )cascade[13]. The hydroosmotic action causes a dramatic increase in the osmotic water permeability of connecting cells, principal cells and inner medullary collecting duct cells. The result is highly concentrated urines produced in response to water restriction.

The success of rodent to survive harsh environment condition goes back to several years ago. However, these animals are faced to substantial anthropogenic threats due to the introduction of heavy metals in environment in the last decades. Cadmium (Cd), a nonessential heavy metal, is widely distributed in the environment due to its use in primary metal industries and phosphate fertilizers [15, 16]. Food and cigarette smoke are the biggest sources of Cd exposure for the general population [17].In humans, Cd exposure leads to a variety of adverse effects and contributes to the development of serious pathological conditions [18-19]linked to enhanced aging process as well as cancer [20-21].Cd produces also neurotoxicity with a complex pathology [22-23]. In animals, Cd was shown to be toxic to all tissues such as liver [24], reproductive organs including the placenta, testis and ovaries [17, 25]. Several studies in some industrial sites in Tunisia showed that some habitats of Merionesshawibecame contaminated by Cd [26-27] Meriones shawihave accumulated cadmium on different organs particularly on kidney and liver. It has been reported that kidneys, which play a major role in hydro-mineral maintenance, are considered to be the organ that is most sensitive to Cd, depending on exposure dose, time and administration route [28]. Several studies indicated that the main critical effect of cadmium exposure is kidney dysfunction. Excretion of low molecular weight proteins is characteristic of damage to the proximal tubules of the kidney. The increased excretion of low-molecular weight proteins in the urine is a result of proximal tubular cell damage [29]. This raises the possibility that body fluid homeostasis and vasopressinergic system could be subtly disrupted by Cd exposure. In this study, we were interested to determine whether Cd naturally incorporated in food would alter the water balance in Meriones shawiwho appears to show a remarkable physiology flexibility of water regulation in both time and space. Effects of Cd exposure upon the water-conserving abilities of this specie were assessed through measurements of water metabolism (total body water (TBW), water influx (Fin), water efflux (Fout) and water turnover rates (WTR) under differing water availabilities. Water fluxes were determined by direct analysis following the principles described by Holleman and Dieterich [30]. Cd effects in the brain were also determined by immunohistochemistry in the supraoptic (SON) and paraventricular (PVN) nuclei at the control level of the central AVP which is the most important hormone in the regulation of water balance in mammals.

Advertisement

2. Material and methods

2.1. Animals and housing conditions

All experiments were carried out on adult male of Muridae; Meriones shawi[31] originating from the south of Tunisia. The rodents were captured from non-polluted regions and kept in captivity in our breeding facility for two generations. The animals were put in single cages and housed in an air-conditioned room maintained at 25 ± 1°C at a relative humidity of 45 ± 10 %, with a 12 h dark-light cycle. The diet of the control group consisted of granular flour mixed with distilled water at the dose of 1 L /1.5 Kg of granular flour. Contaminated diets of treated animals consisted of granule flour mixed with a solution of cadmium chloride (CdCl2) at dose (1 g Cd/1L H2O/1.5 kg of granule flour) [32].Food was given in the form of balls dried at 60 ° C for 72 hours. Water was supplied ad libitum.

Animals were randomly selected and divided into four groups. Eight animals, the first goup was used as control (C). Water was given ad libitum. Merionesof the second group (8 animals) received the same diet but were deprived of water (D-). The third group was treated with Cd in the form of CdCl2 (Cd) at dose (1 g Cd/1L H2O/1.5 kg of granule flour). The last group was also treated with CdCl2 at the same dose but was deprived water D+Cd.

For immunohistochemistry study, treatment period had lasted from eight days to two weeks. Each animal was put in a metabolic cage for eight days in order to collect feces and 24 h urine each day at the same time. Urine samples were collected on paraffin oil to prevent evaporation and measured in mL/day. Daily consumption of drinking water and food of each group were measured throughout the study. It was not possible to collect urine since the 10 days of dehydration.

All of the protocols were carried out in accordance with French standard ethical guidelines for laboratory animals (agreement 75-178, 5_16_2000).

2.2. Techniques

Body weight of each animal was determined throughout the experiment. Blood samples were collected from the infra-orbital sinus into heparinized hematocrit capillary tubes, immediately before the experimental period and eight days later. These samples were centrifuged at 1500 g x for 10 min in order to determine hematocrit. At the end of experimentation rodents were sacrificed by decapitation, and brain, kidneys and livers were immediately removed and weighed. The weight of organs (%) was calculated as g /100 g of body weight. Finally these organs were dried at 60° C and weighed for the determination of dry weight.

2.3. Determination of water fluxes

Water fluxes were determined by direct analysis following the principles described by Holleman and Dieterich [30]. Rates of water flux represent the loss of water via excretion and evaporation and the simultaneous input of water, via metabolic water production and pre-formed water via food and drink (Nagy and Costa 1980). Free water content of the food determined by drying to constant weight at 60 °C was 3 %. The metabolic water content was determined from carbohydrate, fat and protein composition [33]. Thus 1 g of given food contains 0.509 mL of water. The intact unshaven carcasses were sublimated to dryness. The difference between live and dry weight was taken as total body water (TBW).

After determining urine volume and feces weight, urine samples were frozen at -30 °C while the feces were dried for 72 h. Water efflux was calculated as the difference between the influx and total body water. Water fluxes are expressed in H2O mL per day. Finally these fluxes were normalized to the average body weights and expressed in kg-0.82. In small mammals an allometric relationship exists between the water efflux or influx and body weight (W) in kilograms, which is Fin=K.W 0.82 ([34-35], expressed as mL/day/100 g body weight.

2.4. Tissue preparation

Merioneswere anesthetized with sodium pentobarbital (70 mg/kg, i.p; Sanofi, Libourne,France) and perfused transcardially with heparin in physiological saline, followed by 500 mL of a freshly prepared solution of 4 % (wt / vol) paraformaldehyde in phosphate –buffered saline (PBS ; pH=7.4). The brains were rapidly removed and postfixed overnight in 4 % paraformaldehyde at 4 °C. Forty micrometer thick coronal sections were cut with a Vibratome (VT 1000S; Leica, Nussloch, Germany). Brain sections were collected in cold PBS.

2.5. Immunohistochemistry

Free-floating sections were pretreated for 20 min with 3 % hydrogen peroxide in PBS to quench endogenous peroxidase. They were then washed with PBS (3 x 10 min), preincubated for 90 min at room temperature in PBS containing 0.05 %. Triton X-100 and 3 % normal horse serum. Sections were incubated for 36 h at 4 °C with Mouse anti-AVP antibody (1: 5000 dilution).

After incubation, sections were rinsed extensively with PBS (four times, 15 min) and incubated for 1.5 h in a 1/100 dilution of biotin conjugated horse anti-goat antibody and other secondary antibodies. Texas Red conjugated rabbit anti-mouse antibody (1/200; dilution; Jackson ImmunoResearch). For amplification, we used tyramide signal amplification fluorescence system technology (NEN, Boston, MA, USA). For details see Banisadr et al. [36]. After washing, sections were mounted onto gelatin-coated slides in Vectashield (Vector) and observed on fluorescent microscope (BX61; Olympus, Melville, NY) and a connected image-acquisition software (Analysis) was used.

2.6. Statistical analysis

Data are shown as the mean ± SEM. All results were compared to control animals (C), as well as to the Cd-exposed animals (Cd). For all our experiment, a two-way ANOVA was used to analyze the differences between groups, followed by a Dunnett’s test with a threshold of significance of p < 0.05 and p < 0.01 to detect specific differences, using a statistical software package (XLSTAT version 2009.1.1).

Advertisement

3. Results

3.1. Body mass

During the eight days of experimentation, body mass doesn’t change significantly in the control group. Body weight loss represented 5.77 ± 0.05 % in Merionestreated with Cd (expressed in % of initial body weight). A higher significant increase in body weight loss (16 ± 0.19 % of initial body weight) was observed following 8 days of water restriction. The body weight loss (19.34 ± 0.29 %) is greater in the Merionesgroup both water-deprived and treated with Cd.

3.2. Relative weights of organs

Relative weight of liver in controls is an average of 0.05 ± 0.01. Cd exposure significantly altered the relative weight of liver (0.036 ± 0.01) following eight days of treatment. Water restriction had no effect on relative weight of liver as compared to control Meriones.

Decrease in relative weight of liver was also observed in water-deprived group and simultaneously treated with Cd. No differences were found in relative kidney weights (6.8 ± 0.9) in all groups under all experimental conditions.

3.3. Food consumption

Consumption of food was expressed per 100 g of body weight. Control animals consumed an average of 4.5 g/day of food. There was a significant (p<0.01) decrease of food intake in the Cd-exposed group (2.54 ± 0.2 g daily). Food intake of the water deprived groups was similar to that of the controls. When water deprivation was combined with Cd exposure, the decrease in food intake became larger and statistically significant compared with both control (p<0.01) and Cd-exposed groups (p<0.05).

3.4. Hematocrit

After eight days of experimentation, hematocrit(44.32 ± 1.08 %) did not change significantly in any treatment condition as compared to day 1 ( Fig. 3).

3.5. Water metabolism

Water metabolism data are shown in Table 1.

TreatmentInitial body weight (g)Total body water (mL)Total body water (%W)Water influx mLWater efflux mLWater influx ml Kg -0.82 d -1Water efflux mL.Kg-0.82 d -1WTR in (% body water d -1)WTR out (% body water d -1)Urinary osmolality mOs/kg H20Plasma osmolality (mOs/kg H20)
Control117.44
±3.66
62.97
±2.55
55.79
±2.74
10.90
±3.63
10.27
±3.66
63.83
±22.70
60.16
±22.79
17.36
±6.44
16.37
±6.43
1100 ± 2307.6 ± 4.2
Cd-exposed
Meriones
134.41

±19.37
61.09
±5.28
48.38
±5.87
10.04
±3.08
9.34
±3.04
50.50
±11.12
47.11
±11.53
15.51
±4.55
14.43
±4.52
1600 ± 1.9**332 ± 3
Deprived wa
ter Meriones
120.37
±16.85
64.89
±1.23
61.30
±9.28
▴▴
⃰⃰ ⃰
2.17
±0.23
▴▴
⃰⃰ ⃰
1.93
±0.56

⃰⃰ ⃰
12.48
±1.27

⃰⃰ ⃰
11.96
±3.34
▴▴
⃰⃰ ⃰
3.18
±1.06
▴▴
⃰⃰ ⃰
3.12
±0.67
▴▴
⃰⃰ ⃰
1700 ±1.9
345 ± 3
Deprived water and Cd-exposed
Meriones
128.25
±18.67
67.59
±1.36
60.50
±9.99
▴▴
⃰⃰ ⃰
1.73
±0.50
▴▴
⃰⃰ ⃰
1.81
±0.76

⃰⃰ ⃰
9.32
±2.11

⃰⃰ ⃰
9.62
±3.28
▴▴
⃰⃰ ⃰
2.45
±0.73
▴▴
⃰⃰ ⃰
2.66
±1.09
▴▴
⃰⃰ ⃰
1162
±2
307.6 ± 4.2

Table 1.

Effects of Cd exposure on water metabolism (Total Body Water, Water influx, Water efflux, and Water Turnover Rates (WTR)and urinary and plasma osmolalities ) in adult Meriones shawimale under hydrated or deprived water conditions. Data are expressed as mean ± SEM from 6 animals in each group. ⃰⃰⃰ p <0.01significantly different from controls C. p<0.05; ▴▴p<0.01 signifficantly different from Cd-exposed Meriones.

Total body water content in control group was 55.79 ± 2.74 (expressed by % of body weight). Throughout the experiments, body water was not significantly altered in any group. In animals having free access to water, water enters throughmetabolic water production and pre-formed water via food and drink.

The value of water influx was 10.90 ± 3.63 ml/ 63.83 ± 22.79 ml.Kg-0.82.d-1.This water influx (Fin) was not significantly affected in the group treated with Cd in comparison to control group. The loss of water via excretion (urine and fecal) and evaporation was Fout =10.27 ± 3.66 ml/60.16 22.79 ml.kg-0.82.d-1. Water fluxes rate were equal (Fin = Fout). This indicates that animals were in water equilibrium.After, one week of Cd exposure, water flux rates were not significantly affected in the group treated with Cd in comparison to control group and water equilibrium was maintained throughout the experiment.

Following one week of dehydration, the water influx rates was significantly decreased from about 5 times in Meriones treated or not with Cd (p<0.01). Cd exposure may not affected the water intake during our experiment.

In spite variations in water intake in different experimental conditions, all animals were in water equilibrium where water influx (Fin) and efflux (Fout) rates were equal (Fin = Fout).

3.6. Distribution of immunohistochemical staining for AVP

In control Meriones shawi, AVP immunostaining was found to be homogeneously distributed in the large magnocellular neurons of SON (Fig. 2) and PVN (Fig. 3). In agreement with previous, in the absence of Cd ingestion, there was a significant compensatory increase in AVP immunostaining by the SON of deprived animals following eight days of water restriction (Fig. 2C) and two weeks (Fig. 2D) compared to controls animals (fig 2A and B). This increase in AVP immunostaining was also observed in PVN respectively after eight days and two weeks of water restriction (Fig. 3C)and (Fig. 3D) compared respectively to controls animals (fig 3a and B).

Similarly to what was observed for AVP immunostaining in deprived animals without Cd, AVP immunoreactivity is strongly increased in SONfollowing eight days of water restriction (Fig. 2E) and PVN (Fig. 2F) compared to controls animals respectively (Fig.2A) and (Fig.3A). The increase of AVP immunostaining became more important by prolonged experiment for two weeks respectively in SON (Fig. 2F) and PVN (Fig. 3F).

Figure 1.

Effects of Cd exposure on water Water influx and efflux in adultMeriones shawimale under hydrated or deprived water conditions. Data are expressed as mean ± SEM from 6 animals in each group.

However, AVP immunostaining from deprived water animals in the presence of Cd was markedly and significantly lower in SON (Fig. 2G) than in deprived water animals but not treated with Cd for a week (Fig. 2C). This decrease of AVP immunostaining becomes more important following two weeks of treatment (Fig. 2H) in comparison in two weeks deprived water animals not treated with Cd (Fig. 2D). Similar effect of AVP depletion in SON was also observed in PVN in simultaneously deprived water group and Cd-exposed Meriones during eight days (Fig. 3G) and two weeks (Fig. 3H) in comparison to those eight days deprived water group and two weeks deprived water groups and not treated with Cd.

Figure 2.

Effect of Cd exposure on AVP immunoreactivity distribution in the hypothalamic supraoptic nuclei (NSO) inMeriones shawi.Control group (A,B), eight days deprived-water group (C ), two weeks deprived-water group (D), Eight days Cd-exposed group E, two weeks Cd-exposed group ( F ), 8 days Cd-exposed and also deprived water group (G), two weeks Cd-exposed and also deprived water group (H).Water deprivation increased the immunohistochemical signal in SON nuclei (C); this increase became more important following two weeks of water deprivation (D). Similar effect was observed when Meriones are exposed to Cd following one week (E) and two weeks (F). However, Exposure to Cd causes a decrease in immunoreactivity of vasopressin at SON by Merionesdeprived water for a week (G) compared to those water deprived group but not treated with Cd (C). This decrease was also observed after two weeks of treatment (H) as compared to water deprived Meriones(D). Scale bars =100 µm.

Figure 3.

Effect of Cd exposure on AVP immunoreactivity distribution in the hypothalamic paraventricular nuclei (NPV) inMeriones shawi.Control group (A,B), eight days deprived-water group (C ), two weeks deprived-water group (D), Eight days Cd-exposed group E, two weeks Cd-exposed group ( F ), 8 days Cd-exposed and also deprived water group (G), two weeks Cd-exposed and also deprived water group (H).Water deprivation increased the immunohistochemical signal in NPV nuclei (C); this increase became more important following two weeks of water deprivation (D). Similar effect was observed when Meriones are exposed to Cd following one week (E) and two weeks (F). However, Exposure to Cd causes a decrease in immunoreactivity of vasopressin at NPV by Merionesdeprived water for a week (G) compared to those water deprived group but not treated with Cd (C). This decrease was also observed after two weeks of treatment (H) as compared to water deprived Meriones(D). Scale bars =100 µm.

3.7. Effect of Cd on water metabolism

Meriones shawi,success dry and wet seasons by stimulating anti-diuretic and diuretic systems alternately. The maintenance of tonicity of body fluids by within a very narrow physiological range is made possible by well-developed homeostatic mechanisms that control the intake and loss of water [2, 37].This capacity was also observed when Meriones shawiwas treated with Cd under various conditions of water deprivation. Meriones shawiare able to maintain body water (55.79 %) status under water deprivation conditions. The absence of change in hematocrit value observed by deprived water groups treated or not with Cd (45%) suggests that regulatory processes occur, resulting in the maintenance of body water content and increase in urine concentration [38-39]. Whether in nature or under laboratory conditions, control groups were in water equilibrium (water influx = water efflux) [32]. The value of water influx was 10.90 ± 3.63 ml/ 63.83 ± 22.79 ml.Kg-0.82.d-1 (figure 1).This water influx (Fin) was not significantly affected in the group treated with Cd in comparison to control group. The loss of water via excretion (urine and fecal) and evaporation was Fout =10.27 ± 3.66 ml./60.16 ± 22.79 ml.kg-0.82.d-1. Water fluxes rate were equal (Fin = Fout). This indicates that animals were in water equilibrium.After, one week of Cd exposure, water flux rates were not significantly affected in the group treated with Cd in comparison to control group and water equilibrium was maintained throughout the experiment. Following one week of dehydration, the water influx rates was significantly decreased from about 5 times in Meriones treated or not with Cd (p<0.01).Cd exposure appears not to impair this capacity during our experiment. However in water deprived animals there was a lower rate of water influx and efflux compared to controls. This low rate of water influx and efflux was similar in water deprived animals and treated with Cd simultaneously (water metabolism are shown in table 1).

The urinary osmolality (UO) in the control Merionesgroup was around 1100 mOsm.Kg-1.H20. The mean value increased significantly from 1100 mOsm Kg-1H20/ to 1600 mOsm.Kg-1 H20 following one week of water restriction.This value not change when animals were exposed to Cd [40]. The plasma osmolality (PO) was around 270 mOsm.Kg-1. It was not changed in all groups following one and two weeks of experiment.Hematocrit was around (44.32 ± 1.08 %). It did not change in any treatment condition as compared to day 1. All these results are shown intable 1.

In spite of the variations in water metabolism, all animals were in water equilibrium, at the end of experimentation. All these results indicate that even under the most stringent conditions Meriones shawihas a strong capacity to maintain a homeostasis state. It seems evident that water restriction induced a pronounced body mass loss in animals after eight days of treatment without available drinking water. This indicates a depletion of reserves of endogenous metabolic water supplies as an alternative to fresh water [9]. Although changes in body mass in Cd-exposed animals are assumed to be due to reduction of daily consumption of food, this decrease of food uptake became larger in animals both deprived water and treated with Cd. This is in agreement with the findings of Pettersen et al. [41]who demonstrated that rats exposed to Cd become anorexic. An important finding in this study, described by other authors Woltowski et al. [42]and Leffel et al. [43] was the early occurrence of Cd induced hepatic damage manifested by lower liver weight, which was explained by the high level of Cd found in livers of exposed animals. As shown by Sudo et al.[44] Cd preferentially localizes in hepatocytes after administration, and its concentration may exceed the capacity of intracellular constituents, mainly metallothioneins (MTs) to bind Cd [45]. MT-bound Cd then appears in the blood plasma [44] and is efficiently filtered through the glomeruli, and subsequently taken up by the tubules leading to its accumulation in kidney [46-47].

In order to maintain physiological serum osmolality, water intake and water loss are finely balanced by Meriones shawieven under water restriction and Cd exposure condition (fig 1). It appears that Meriones shawiare able to retain water by excretion of highly concentrated urine [8]. Water loss was also limited by the lowered faecal water loss achieved by the production of very dry feces. In deprived water Meriones we show that water intake was provided from preformed water of food and by metabolic water production as described by Speakman [48]and King and Bradshaw [49]. Our findings are in agreement with previous reports showing that renal concentrating mechanisms are the first line of defense against water depletion [4, 12, 50]. It is well established that modifications of serum osmolality during depletion are detected via osmoreceptors by magnocellular mainly located in the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) in the brain [39, 51]. These neurons increase their electrophysiological activity during water restriction leading to an increase of AVP synthesis [52- 53] (and facilitates sustained antidiuresis [54] (De Mota et al. 2004). In contrast to what was observed in the laboratory rat where dehydration causes a dramatic depletion of hypothalamic AVP immunoreactivity in both SON and PVN [55- 56],water restriction induced in our model an increase in expression of AVP. This increase becomes more important with time of restriction water.

Interestingly, the ability of acute systemic dehydration to produce AVP in both SON and PVN in Meriones shawideprived water and not treated with Cd, was also observed while treating Meriones with Cd but not deprived water. We hypothesized that potential effects of Cd might include exaggerated synthesis of AVP during Cd exposure in our model Meriones shawiand support the idea of an increase of AVP as result of Cd intoxication (see figure 2 and 3). These findings suggest that Cd ingestion has potential effects on the vasopressinergic system that responds with elevated synthesis of AVP under stimulated conditions [57]. A large number of studies have demonstrated that Cd exposure produce marked neuroendocrine changes in animals [58- 59] and human [60].

The current study is the first to explore the potential impact of Cd exposure on the magnocellular neuroendocrine system responsible for hydromineral balance. In this paper, we shown an involvement of the hypothalamo-vasopressinergic system of AVP, wish plays a fundamental role in the maintenance of body fluid homeostasis, in the protective reactions of the organism during Cd exposure in Meriones shawiby secreting arginine-vasopressin in response to a variety of physiological stimuli, including osmotic [61-63] and nonosmotic stimuli [64, 65]. In support of this, we found that water metabolism was identical in both groups of deprived water Merionesand treated Merioneswith Cd respectively. In contrast, the adaptive response of vasopressin enhancement secretion in both SON and PVN under stimulated conditions as dehydration or Cd exposure in Meriones shawi,was attenuated in Meriones simultaneously exposed to Cd and dehydration of water, as compared to deprived water but not treated with Cd group.Our results show an inhibitory effect of Cd exposure on AVP immunoreactivity in both SON and PVN in response to acute water restriction in adult male Meriones.We hypothesized that potential effects of Cd might modifies vasopressinergic system which is amplified under water restriction, where AVP neurons are under constant stimulation and suggested that vasopressinergic system is subtly disrupted. Similar effect of AVP depletion in both SON and PVN, produced by Cd ingestion in deprived water was also observed in deprived water laboratory rats treated by an organochlorine pollutant (polychlorinated biphenyls (PCBs) during 15 days [66]. According to these authors, the AVP decline was attributable to specific effects of overt toxicity and/or malaise oral of PCBs on vasopressinergic hypothalamic cells function. In combination with the efficacy of in vitroapplication, these data are consistent with direct actions on components of the hypothalamo-neurohypophysial system present within the SON [67-68]. PCBs has been reported to inhibit nitric oxide synthase activity. It is noteworthy that the inhibition of nitric oxide production in SON tissue punches produces a virtually identical, selective effect on dehydration stimulated intranuclear AVP release in vitro[69] and has been reported to exaggerate pituitary depletion of AVP in the intact deprived water rat [70].

Most strikingly, vasopressin is recognized as circulating hormone. Its actions were essentially confined to peripheral organs. However, currently AVP have been shown to be released in the brain as chemical messengers. AVP, like many peptides, when released within the brain, plays an important role in social behaviour. In rats, AVP is implicated in paternal behaviors, such as grooming, crouching over and contacting pups. AVP is also important for partner preference and pair bonding, particularly for males in a variety of species. It has been shown that AVP has powerful influences on complex behaviours [71].Disruption of vasopressinergic system has been linked to several neurobehavioural disorders including prader-Willi syndrome, affective disorders, obsessive-compulsive disorder and polymorphisms of V1a vasopressin receptor have been linked to autism [72].

Advertisement

4. Conclusion

On the basis of the current study, we conclude that Cd exposure modifies the vasopressinergic neuronal system and provides information regarding the neurotoxicity risks that this element presents for mammals and human populations exposed to Cd even to low amounts without affecting directly water metabolism. We are currently trying to study the linkage between Cd exposure and water controlling behavior at different level of the central nervous system.

References

  1. 1. WillmerP.StoneG.JohnstonI. M.Environmental Physiology of Animals.Blackwell Science, Oxford2000
  2. 2. Nagy KA.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiInt Cong series20041275291297
  3. 3. ElgotA.AhbouchaS.MMBouyatasMontange. M. F.GamraniH.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiNeurosci. Lett.2009466610
  4. 4. BozinovicF.GallardoP.The water economy of South American desert rodents: From integrative to molecular physiological ecology Review.Comp. Biochem. Physiol. C. Toxicol. Pharmacol2006
  5. 5. Corbet GB.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiBritish Museum (Natural History), Cornell University Press.1978
  6. 6. GamraniH.ElgoA.El HibaO.Fèvre-MontangeM.Cellular plasticity in the supraoptic and paraventricular nuclei after prolonged dehydration in the desert rodent Meriones shawi: Vasopressin and GFAP immunohistochemical studyBrain. Res.201113758592
  7. 7. King JM, Bradshaw SD.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiGen Comp Endocrinology20081552378385
  8. 8. RabhiM.UgrumovM. V.GoncharevskayaO. A.BengellounW.CalasA.NatochinY. V.Developmentof.thehypothalamic.vasopressinsystem.nephronsin.Merionesshawi.duringontogenesis.AnatEmbryol. .Berl19961933281296
  9. 9. Ben-ChekirChaouacha.R.Fonction thyroidienne et métabolisme hydrique chez quelques gerbillidés du sud tunisien.1989Thèse doct. d’état. Museum National d’Histoire naturelle et Université Pierre et Marie Curie, Paris 6.
  10. 10. DoucetA.BarletC.BaddouriK.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiPflugers Arch.1987408129132
  11. 11. SellamiA.MaurelD.KosaA.SicudP.Réponses hormonales du mérion, un rongeur désertique à la privation d’eau prolongée : comparaison avec le rat. Mésogée200561117
  12. 12. BaddouriK.ButlenD.Imbert-TeboulM.Le BouffantF.MarchettiJ.ChabardesD.MorelF.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiGen. Comp. Endocrinol.198454203215
  13. 13. BirnbaumerM.SeiblodA.GilbertS.IshidoM.BarberisC.AntaramianA.BrabetP.RoesnthalW.Molecular cloning of the receptor for human antidiuretic hormone. Nature1992357333335
  14. 14. BenChaouacha-chekir. R.LeloupJ.LachiverF.Influence of thyroid status on water metabolism and survival of normal and deprived water desertrodents Meriones libycus. Gen Comp Endocrinol199710518
  15. 15. Morselt AFW.Environmental pollutants and disease. Toxicology1991;701132.
  16. 16. NovelliE. L. B.VieiraE. P.RodriguesN. L.RribasB.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiEnviron Res.791998 A102105
  17. 17. Waalkes MP, Coogan TP, Barter RA.Toxicological Principles of Metal Carcinogenesis with Special Emphasis on Cadmium.Critical Rev in Toxicol1992
  18. 18. Bernard A.Renal dysfunction induced by cadmium: biomarkers of critical effects.Biometals2004175519523
  19. 19. JinT.NordbergG.YeTingting. B. O. M.WangH.ZhuG.KongQ.BernardA.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiEnviron Res200496353369
  20. 20. Waalkes MP. Cadmium carcinogenesis. Mutat Res2003
  21. 21. HuffJ.LunnR. M.WaalkesM. P.TomatisL.InfanteP. F.Cadmium-inducedcancers.inanimals.inhumans.Int J Occup Environ Health.2007132202212
  22. 22. Shukla GS, Singhal RL.The present status of biological effects of toxic metals in the environment : lead, cadmium, and manganese.Can J Physiol Pharmacol19846210151031
  23. 23. GuptaA.GuptaA.MurthyR. C.ChandraS. V.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiBull Environ Contam Toxicol1993511217
  24. 24. Newairy AA, El-Sharaky AS, Badreldeen MM, Eweda SM, Sheweita SA.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiToxicology200723 EOF
  25. 25. LeffelE. K.WolfC.PoklisA.White JrK. L.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiToxicology2003188233250
  26. 26. MessaoudiI.BenChaouacha-chekir. R.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawii. Mammalia2002t664553562
  27. 27. SebeiA.chaabaniF.OuerfelliM. K.AbdeljaouedS.Evaluation de la contamination des sols par des métaux lourds dans la région minière de Fedj Lahdhoum (NW de la Tunisie). Revue Méditérranéenne de L’Environnement2006112
  28. 28. YasudaM.MiwaA.KitagawaM.Morphotometric studies of renal lesions in Itai-Itai disease : Chronic cadmium nephropathy. Nephron1995691419
  29. 29. IkedaM.EzakiT.TsukaharaT.MoriguchiJ.FurukiK.FukuiY.UkaiS. H.SakuraiH.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiBiometals200417539541
  30. 30. Holleman DF, Dietrich RA.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiJ Mamm.197354456465
  31. 31. Nicol SC.Rates of water turnover in Marsupials and Eutheriens: a comparative review with new data on the Tasmanian Devil. Austr J Zool197826465473
  32. 32. ChevretP.DobignyG.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiMol Phylogenetics Evol200535674688
  33. 33. MbarekS.SaidiT.BenMansour. H.RosteneW.ParsadaniantzS. M.BenChaouacha-chekir. R.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiEnviron. Eng. Sci.2011283237248
  34. 34. KleiberM.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiWiley, New York. (1961pp.
  35. 35. PetterF.LachiverF.ChekirR.Les adaptations des rongeurs Gerbillidés à la vie dans les régions arides. Bull Soc Bot Fr (1984
  36. 36. NagyK. A.CostaD. P.Water flux in animals : analysis of potential errors in the tritiated water method. Am. J. Physio.1980R454R465.
  37. 37. BanisadrG.FontangesP.HaourF.KitabgiP.RosteneW.Parsadaniantz. S. M.Neuroanatomical distribution of CXCR4 in adult ratbrain and its localization in cholinergic and dopaminergic neurons. Eur J Neurosci2002161661
  38. 38. De RouffignacC.MorelF.Etude comparée du renouvellement de l’eau chez quatre espèces de rongeurs, dont deux espèces d’habitat désertique. J Physiol Paris196558309322
  39. 39. Nagy KA.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiInt Cong series20041275291297
  40. 40. Lacas-GervaisS. G.MaurelD.HubertF.AllevardA. M.DoukaryA.MaggiV.Siaud. P.GharibC.SicardB.CalasA.Hardin-PouzetH.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawin. Gen.Comp. Endocrinol.2003133132
  41. 41. MbarekS.SaidiT.González-CostasJ. M.González-Romeroand Ben Chaouacha ChekirR, Effects of dietary cadmium on osmoregulation mechanism and urine concentration mechanisms of the semi desert rodent Meriones shawi,Journal of environmental monitoring2012acceptedDOI: 10.1039/C2EM30121K.
  42. 42. PettersenA. J.AndersenR. A.ZachariassenK. E.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiComp Biochem PhysiolC20021325360
  43. 43. WlostowskiT.KarasowskaA.Laszkiewicz-tiszczenkoB.Dietary cadmium induces histopathological changes despite a sufficient metallothionein level in the liver and the Kidneys of the bank vole Cletheriomys glareolus. Comp Biochem Physiol C.20001262188
  44. 44. LeffelE. K.WolfC.PoklisA.White JrK. L.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiToxicology2003188233250
  45. 45. SudoJ.HayashiT.KimuraS.KakunoK.TeruiJ.TakashimaK.SoyamaM.Mechanism of nephrotoxicity induced by repeated administration of cadmium chloride in rats.J Toxicol Environ Health.1996484333348
  46. 46. XuL. C.SunH.WangS. Y.SongL.ChangH. C.WangX. R.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiEnviron Toxicol pharmacol2005208387
  47. 47. MMBrzóskaKamiński. M.Supernak-BobkoD.ZwierzK.Moniuszko-Jakoniuk. J.Changes in the structure and function of the kidney of rats chronically exposed to cadmium.I.Biochemical and histopathological studies. Arch Toxicol200377344
  48. 48. LynesM. A.ZaffutoK.UnfrichtD. W.MarusovG.JacquelineS.SamsonJ.YinX.ThePhysiological.Rolesof.ExtracellularMetallothionein.Exp Biol Medicine200623115481554
  49. 49. SpeakmanJ. R.DoublyLabeled.WaterTheory.PracticeLondon.ChapmanHall-1997pp.
  50. 50. King JM, Bradshaw SD.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiGen Comp Endocrinology2008378 EOF385 EOF
  51. 51. BozinovicF.GallardoP.VisserG. H.CortesA.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiJ Exp Biol200320629592966
  52. 52. WakerleyJ. B.PoulainD. A.BrownD.Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawiBrain Res1978148244254440
  53. 53. ArnauldE.DufyB.JDVincentHypothalamic.supraopticneurones.ratespatternsof.actionpotential.firingduring.waterrestriction.inthe.unanaesthetizedmonkey.Brain Res19751002315325
  54. 54. HirumaM.OgawaK.TaniguchI. K.Immunocytochemical and morphomometric studies on the effects of dehydration on vasopressin-secreting cells in the hypothalamus of the Mongolian gerbils. J Vet Med Sci1992545881889
  55. 55. De MotaN.Reaux LeGoazigo. A.El MessariS.ChartrelN.RoeschD.Dujardin. C.KordonC.VaudryH.MossoF.LlOrens-cortes. C.Apelina.potentdiuretic.neuropeptidecounteracting.vasopressinactions.throughinhibition.ofvasopressin.neuronactivity.vasopressinrelease.Proc Natl Acad Sci2004101281046410469
  56. 56. CallewaereC.BanisadrG.DesarménienM. G.DesarménienM. G.MechighelP.Kitabgi. P.RostèneW. H.ParsadaniantzS. M.Thechemokine. S. D.F-C. X. C. L.modulatesthe.firingpattern.ofvasopressin.releasethrough. C. X. C. R.Neuroscience20061032182218226
  57. 57. CallewaereC.FernetteB.RaisonD.MechighelP.BurletA.CalasA.KitabgiP.MelikParsadaniantz. S.RosteneW.Cellular and subcellular evidence for neuronal interaction between the chemokine stromal cell-derived factor-1/CXCL12 and vasopressin: regulation in the hypothalamo-neurohypophysial system of the Brattleboro rats. Endocrinology20081491310319
  58. 58. EngelmannM.LudwigM.The Activity of the Hypothalamo-Neurohypophysial System in Response to Acute Stressor Exposure: Neuroendocrine and Electrophysiological Observations. Stress2004729196
  59. 59. AntonioM. T.CorpasL.LeretM. L.Neurochemical changes in newborn rats brain after gestational cadmium and lead exposure. Toxicol let1999
  60. 60. Méndez-armentaM.Villeda-hernandezJ.Barroso-moguelR.Nava-ruizC.MEJimenez-capdevilleRios. C.Brain regional lipid peroxidation and metallothionein levels of developing rats exposed to cadmium and dexamethasone. Toxicol Lett2003144151157
  61. 61. GuptaA.GuptaA.ShuklaS. G.Development of brain free radical scavenging system and lipid peroxidation under the influence of gestational and lactational cadmium exposure. Hum ExpToxicol199514428433
  62. 62. LudwigM.HornT.CallahanM. F.GroscheA.MorrisM.LandgrafR.Osmoticstimulation.ofthe.supraopticnucleus.centralperipheralvasopressin.releasebloodpressure.AmJ.Physiol1994Pt 1):E351E356.
  63. 63. BundzikovaJ.PirnikZ.ZelenaD.JDMikkelsenKiss. A.Responseof.substancesco-expressed.inHypothalamic.magnocellularneurons.toosmotic.challengesin.normalbrattlebororats.Cell Mol Neurobiol200828810331047
  64. 64. Llorens-cortesC.MoosF.Opposite potentiality of hypothalamic coexpressed neuropeptides, apelin and vasopressin in maintaining body-fluid homeostasis. Prog Brain Res.2008170559570
  65. 65. AguileraG.LightmanS. I.kissA.Regulation of the hypothalamic-pituitary-adrenal axis during water restriction. Endocrinology1993132241248
  66. 66. KregelK. C.StraussH.UngerT.Modulation of autonomic nervous system adjustments to heat stress by central ANGII receptor antagonism. Am J Physiol1994R1985R1991.
  67. 67. CoburnC. G.GillardE. R.Curras-CollazoM. C.Dietary exposure to Aroclor 1254 alters centra and peripheral vasopressin release in response to dehydration in the rat. Toxicol. Sci. 84, 149.
  68. 68. KangJ. H.JeongW.ParkY.LeeS. Y.ChungM. W.LimH. K.ParkI. S.ChoiK. H.ChungS. Y.DSKimPark. C. S.HwangO.KimJ.Aroclor 1254-induced cytotoxicity in catecholaminergic CATH a cells related to the inhibition of NO production. Toxicology2002177157166
  69. 69. SharmaR.KodavantiP. R.In vitro effects of polychlorinated biphenyls and hydroxy metabolites on nitric oxide synthases in rat brain. Toxicol Appl Pharmacol2002178127136
  70. 70. GillardE. R.CoburnC. G.BauceL. G.PittmanQ. J.Curra´s-CollazoM. C.Nitric oxide is required for vasopressin release in the supraoptic nucleus (SON) in response to both PACAP and dehydration. Program6602004Abstract Viewer/Itinerary Planner, Washington, DC: Society for Neuroscience, Online.
  71. 71. KadowakiK.KishimotoJ.LengG.EmsonP. C.Up-regulation of nitric oxide synthase (NOS) gene expression together with NOS activity in the rat hypothalamo-hypophysial system after chronic salt loading: Evidence of a neuromodulatory role of nitric oxide in arginine vasopressin and oxytocin secretion. Endocrinology199413410111017
  72. 72. DonaldsonZ. R.YoungL. J.Oxytocinvasopressin.theneurogenetics.ofsociality.Science2008322900904
  73. 73. Insel TR.The challenge of translation in social neuroscience: a review of oxytocin, vasopressin and affiliative behavior. Neuron201065768779

Written By

Sihem Mbarek, Tounes Saidi and Rafika Ben Chaouacha-Chekir

Submitted: November 30th, 2011 Reviewed: June 4th, 2012 Published: September 19th, 2012