**1. Introduction**

146 Neuroendocrinology and Behavior

136(8): 1146-1152.

Sciences, 83): 41-48.

Bull.,69(1):48-56.

261-270.

R264-R273.

Cajal. World J Gastroenterol 141(8): 2882-2887.

Wiley KE, Davenport AP (2002) Comparioson of vasodilators in human internal mammary artery: ghrelin is a potent physiological antagonist of endothelin-1. Br J Pharmacol,

Xu D, Yu BP, Luo HS, Chen LD (2008) Control of gallbladder contractions by cholecystokinin through cholecystokinin-A receptors on gallbladder interstitial cells of

Yamada S, Takeuchi C, Oyunzul L, Ito Y (2009). Bladder angiotensin-II receptors: characterization and alteration in bladder outlet obstruction. Eur Urol, 55(2): 482-489. Yankov K (2006) System Identification оf Biological Processes. Proc. 20-th Int.Conf. "Systems for Automation of Engineering and Research SAER-2006. Varna, Bulgaria, 144-149. Yankov K (2009) Recognition and function association of experimental data. Proc. of the Int. Conference on Information Technologies InfoTech-2009, Varna, Bulgaria, 131-141. Yankov K. (2010) Preprocessing of Experimental Data in Korelia Software. Trakia Journal of

Yankov K (2011) Evaluation of characteristic parameters of dynamic models. Proceedings of the International Conference on Information Technologies InfoTech-2011,15th – 17

Yannielli P, Molyneux P, Harrington M, Golombek D (2007) Ghrelin Effects on the Circadian

Zelena D, Mergl Z, Makara GB (2006) The role of vasopressin in diabetes mellitus-induced hypothalamo-pituitary-adrenal axis activation: studies in Brattleboro rats.Brain Res

Zetler G (1983) Neuroleptic-like effects of ceruletide and cholecystokinin octapeptide: interactions with apomorphine, methyphenidate and picrotoxin. Eur J Pharmacol 94,

Zhang J, Ritter RC (2012) Circulating GLP-1 and CCK-8 reduce food intake by capsaicininsensitive, nonvagal mechanisms. Am J Physiol Regul Integr Comp Physiol 302(2):

September 2011, Bulgaria, http://www.tu-sofia.bg/saer/index.html.

System of Mice. The Journal of Neuroscience, 271(1): 2890 –2895.

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 restriction until several months [6]. It appears that water 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 shawi* produces 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 shawi* submitted 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

© 2012 Mbarek et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Mbarek et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

important hormone to elaborate urines largely hyperosmotic to plasma. A comparative study of water controlling behavior was done between rat laboratory and *Meriones shawi* demonstrated 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].

Effect of Cadmium Contaminated Diet in Controlling Water Behavior by *Meriones shawi* 149

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

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

Animals were randomly selected and divided into four groups. Eight animals, the first goup was used as control (C). Water was given *ad libitum*. Meriones of 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

All of the protocols were carried out in accordance with French standard ethical guidelines

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

water balance in mammals.

**2. Material and methods** 

the 10 days of dehydration.

**2.2. Techniques** 

dry weight.

**2.1. Animals and housing conditions** 

balls dried at 60 ° C for 72 hours. Water was supplied *ad libitum*.

for laboratory animals (agreement 75-178, 5\_16\_2000).

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 *Meriones shawi* became contaminated by Cd [26-27] *Meriones shawi* have 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 shawi* who 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.
