Behaviour of Tunisian Psammomys obesus fed high-calorie diets: biochemical disturbance and histopathological alterations.

This work investigated the biochemical disturbances and histological alteration in Psammomys obesus animal model fed different high calorie diets (HCDs) during three months. Four diets were used: a low-calorie natural diet, Chenopodiaceae halophyte plant used as control (LCD), a high standard carbohydrate diet rich in protein, HCD 0, a high carbohydrate diet rich in two concentrations of fat, HCD 1 and HCD 2. All animals having received HCDs developed dyslipidemia after one month of experiment with distinction of different sub-groups developing or not obesity and diabetes. HCDs induced a remarkable increasing in blood cholesterol, LDL-cholesterol and triglyceride levels indicating a fast induction of dyslipidemia and a significant increase of aminotransaminases activities revealing a pronounced hepatotoxicity. Animal developing diabetes showed a severe hepatic injury, a degeneration of the adipose tissue and a significant reduction of retinal thickness. P. obesus seems to be an excellent animal model to investigate nutritional metabolic diseases.

Anti-Obesity and Anti-Dyslipidemic Effects of Salicornia arabica Decocted Extract in Tunisian Psammomys obesus Fed a High-Calorie Diet.

Salicornia is a halophyte plant that has been used in traditional medicine for the treatment of scurvy, goiter, and hypertension. It is commercialized in Europe and Asia as fresh salads, pickled vegetables, green salt, or tea powder. This work is the first to assess the potential anti-obesity and anti-dyslipidemic effects of Salicornia arabica decocted extract (SADE). SADE was characterized by its significant in vitro radical scavenging activity (using DPPH and ABTS assays). The effect of SADE on food intake, weight loss, serum biochemical parameters, liver and kidney weights, adiposity index and on liver histology was investigated in the Tunisian gerbil Psammomys obesus (P. obesus), which is recognized as a relevant animal model of human obesity and diabetes. P. obesus animals were firstly randomly divided into two groups: the first received a natural low-calorie chow diet (LCD), and the second group received a high-calorie diet (HCD) over 12 weeks. On day 90, animals were divided into four groups receiving or not receiving SADE (LCD, LCD + SADE, HCD, and HCD + SADE). If compared to the HCD group, SADE oral administration (300 mg/kg per day during 4 weeks) in HCD + SADE group showed on day 120 a significant decrease in body weight (-34%), blood glucose (-47.85%), serum levels of total cholesterol (-54.92%), LDL cholesterol (-60%), triglycerides (-48.03%), and of the levels of hepatic enzymes: ASAT (-66.28%) and ALAT (-31.87%). Oral administration of SADE restored the relative liver weight and adiposity index and significantly limited HCD-induced hepatic injury in P. obesus. SADE seems to have promising in vivo anti-obesity and anti-dyslipidemic effects.

Effects of dietary cadmium exposure on osmoregulation and urine concentration mechanisms of the semi-desert rodent Meriones shawi.

Contamination by cadmium in the environment is of great concern because of its toxicity and threats to human and animal health. The current study was conducted to investigate the effects of a cadmium contaminated diet on the osmoregulation and urine concentration mechanisms of the semi-desert rodent Meriones shawi and eventual accumulation of this metal in vital organs such as the kidneys, which are directly implicated in water regulation. Originally, we used Differential Pulse Anodic Stripping Voltammetry (DPASV) to avoid the matrix interference due to the highly organic content in the biological samples. Our results show that Meriones shawi successfully maintained a homeostasis state and presented a special adaptation to regulate urine volume during cadmium exposure by decreasing diuresis and increasing urinary osmolality. The plasma osmolality and hematocrit remained constant throughout the experiment. The stripping signals of cadmium are linear up to 0.3-100 µg L(-1) range, with a detection limit of 0.28 µg L(-1). The DPASV technique was useful for easy, fast, selective and sensitive determination of Cd, which permits working at cellular concentration. This gives us more information about the chemical form in which Cd is introduced into the organ, as well as the intracellular Cd quantities. This study has potential importance if this valuable novel animal model, imitating human and animal environmental chronic exposure to Cd, could serve as an appropriate terrestrial biomonitor for Cd contaminated sites. These results are encouraging in the context of developing a low-cost and fast technology for the detection of pollutants and for studying the impairment caused by their effects.

Neuroprotective effects of oleuropein on retina photoreceptors cells primary culture and olive leaf extract and oleuropein inhibitory effects on aldose reductase in a diabetic model: Meriones shawi.

Aldose reductase (AR) is an enzyme implicated in the development of diabetes complications among them diabetic retinopathy. Erythrocyte AR activity was measured in control and diabetic Meriones shawi, a type-2 diabetic model. We noticed an increase of AR activity in diabetic Meriones by comparison to controls. Olive leaf aqueous extract and oleuropein were tested for their inhibitory potential on AR activity. Both exerted a partial in-vitro inhibition effect which was higher with the olive leaf extract. The ex-vivo protective effect of oleuropein was tested in photoreceptors rod and Mcône retinal cells of Meriones shawi in hyperglycaemic conditions. Mixed retinal cells were cultured at 25 mM glucose for 5 days and treated with oleuropein. Cell viability was assessed using MTT test and trypan blue exclusion dye. Rod and Mcône Photoreceptors were characterised by immuno-cytochemistry. Oleuropein protected retinal cells against the toxic effect of glucose by improving the viability of photoreceptors.

Correlation between antibutyrylcholinesterasic and antioxidant activities of three aqueous extracts from Tunisian Rhus pentaphyllum.

For centuries, plants have been used in traditional medicines and there has been recent interest in the chemopreventive properties of compounds derived from plants. In the present study, we investigated the antibutyrylcholinestrasic (anti-BuChE) and antioxidant (against some free radicals) activities of extracts from Rhus pentaphyllum. Aqueous extracts were prepared from powdered R. pentaphyllum roots, leaves and seeds and characterized for the presence of tannins, flavonoids and coumarins. Seeds aqueous extract contained the highest quantities of both flavonoids and tannins (21.12% and 17.45% respectively). In the same way, seeds extracts displayed remarkable inhibition against BuChE over 95%, at 100 µg/ml and with IC50 0.74 µg/ml. In addition, compared to leaves and roots extracts, seeds aqueous extract revealed relatively strong antiradical activity towards the ABTS.+ (IC50 = 0.25 µg/ml) and DPPH (IC50 = 2.71 µg/ml) free radicals and decreased significantly the reactive oxygen species such O2.- (IC50 = 2.9 µg/ml) formation evaluated by the non-enzymatic generating O2.- system (Nitroblue tetrazolium/riboflavine). These data suggest that the anti-BuChE activities mechanism of these extracts occurs through a free radical scavenging capacities.The present study indicates that extracts of Rhus pentaphyllum leaves, seeds and roots are a significant source of compounds, such as tannins, flavonoids and coumarins, with anti-BuChE and antioxidant activities, and thus may be useful for chemoprevention.

Diurnal rodents as animal models of human central vision: characterisation of the retina of the sand rat Psammomys obsesus.

BACKGROUND: Cone photoreceptor-based central vision is of paramount importance in human eyesight, and the increasing numbers of persons affected by macular degeneration emphasizes the need for relevant and amenable animal models. Although laboratory mice and rats have provided valuable information on retinal diseases, they have inherent limitations for studies on macular pathology. In the present study, we extend our recent analyses of diurnal murid rodents to demonstrate that the sand rat Psammomys obesus has a remarkably cone-rich retina, and represents a useful adjunct to available animal models of central vision. METHODS: Adult P. obesus were captured and transferred to animal facilities where they were maintained under standard light/dark cycles. Animals were euthanised and their eyes enucleated. Tissue was either fixed in paraformaldehyde and prepared for immunohistochemistry, or solubilized in lysis buffer and separated by SDS-PAGE and subjected to western blot analysis. Samples were labelled with a battery of antibodies against rod and cone photoreceptors, inner retinal neurones, and glia. RESULTS: P. obesus showed a high percentage of cones, 41% of total photoreceptor numbers in both central and peripheral retina. They expressed multiple cone-specific proteins, including short and medium-wavelength opsin and cone transducin. A second remarkable feature of the retina concerned the horizontal cells, which expressed high levels of glial fibrillar acidic protein and occludin, two proteins which are not seen in other species. CONCLUSION: The retina of P. obesus displays high numbers of morphologically and immunologically identifiable cones which will facilitate analysis of cone pathophysiology in this species. The unusual horizontal cell phenotype may be related to the cone distribution or to an alternative facet of the animals lifestyle.

Functional alterations of retinal neurons and vascular involvement progress simultaneously in the Psammomys obesus model of diabetic retinopathy.

To investigate the progression of diabetic retinopathy (DR) in a new diurnal animal model, we monitored clinically the DR in Psammomys obesus (P. obesus) during 7 months using electroretinography (ERG) and imaging techniques. After the onset of DR, all ERG components decreased progressively. In scotopic conditions, by 3-months of disease progression, the diabetic P. obesus displayed a significant decrease in amplitude of b-max, b-wave responses, and mixed b-waves. While mixed a-wave decreased between 4 and 7 months. Significant differences of OP2 appeared following 1 month of disease. In photopic conditions, we noticed a decrease in the a-wave at 2 months, while it took more than 5 months in b-wave amplitude. The photopic negative response (PhNR) and the i-wave amplitudes decreased following 4 and 5 months. OP1 and OP2 were the first to be altered and a significant decrease in the amplitude started after 3 months. Finally, 30 Hz-flicker and photopic S-cone were impaired after 2 and 3 months, respectively. The assessment of the eye fundus of the retina revealed an abnormal vascular architecture appeared at Months 6 and 7. In addition, we noticed exudates in the superior periphery of the retina at the same stage. The retina thickness showed a significant reduction at Month 7. Our results indicate that the clinical correlates of human DR are present in diabetic P. obesus. The depressed of ERGs, disruption of retinal architecture, and the appearance of exudates may reflect vascular and neuronal damage throughout the retina as are seen in the advanced stages of human DR.

Study of retinal alterations in a high fat diet-induced type ii diabetes rodent: Meriones shawi.

Diabetic retinopathy is a common complication of type 2 diabetes and the leading cause of blindness in adults of working age. The aim of this work was to study the repercussions of high fat diet (HFD) induced diabetes on the retina of Meriones shawi (M.sh). Two groups of six M.sh each was studied. Group I was a normal control, fed with standard laboratory granules. In Group II, rodents received a HFD of enriched laboratory granules, for a period of 3 months. Body weight and plasma glucose were determined in the two groups. Retinal sections of the two groups were stained with the Hematoxylin-Eosin. Photoreceptors were identified by immunolabeling for rhodopsin (rods) and PNA (cones). Gliosis and microglial activation were identified by immunolabeling for GFAP and Iba-1. Labeling of calretinin and parvalbumin were also carried out to study the AII amacrine cells. Retinal layers thicknesses, gliosis, and specific neural cell populations were quantified by microscopy. The body weight (+77%) and plasma glucose (+108%) were significantly greater in the HFD rodents. Three months of HFD induced a significant loss of 38.77% of cone photoreceptors, as well as gliosis and an increase of 70.67% of microglial cells. Calcium homeostatic enzymes were depleted. This work shows that HFD in Meriones shawi induces a type II diabetes-like condition that causes loss of retinal neurons and photoreceptors, as well as gliosis. Meriones shawi could be a useful experimental animal model for this physiopathology particularly in the study of retinal neuro-glial alterations in Type II diabetes.

Characterizing the Retinal Function of Psammomys obesus: A Diurnal Rodent Model to Study Human Retinal Function.

PURPOSE: To compare the retinal function of a diurnal murid rodent, Psammomys obesus, with that of Wistar albino rat and human subjects. MATERIALS AND METHODS: Adult Psammomys obesus were captured and transferred to the animal facilities where they were maintained at 25°C with standard light/dark cycles and natural halophilic plants, rich in water and mineral salts. Standard full-field photopic and scotopic electroretinograms were obtained. RESULTS: The right eye of all animals displayed well detectable and reproducible scotopic and photopic electroretinogram (ERG) responses. Results were compared with those obtained from human subjects and Wistar rats. ERG measurement showed that the amplitudes of scotopic responses in Psammomys obesus are quite similar to those of human subjects. The amplitude of the photopic a-wave was comparable to that of humans and six times higher than that of the albino rat. The amplitudes of photopic b-wave, photopic oscillatory potentials (OPs), and 30 Hz flicker were all markedly larger in Psammomys obesus compared to those obtained from human subjects and Wistar rats. Furthermore, like the human photopic ERG, the photopic ERG of Psammomys obesus also includes prominent post b-wave components (i.e. i- and d-waves) while the ERG of Wistar rats does not. CONCLUSIONS: Our results suggest that the retinal function of Psammomys obesus, especially the cone-mediated function, shares several features with that of human subjects. We believe that Psammomys obesus represents an interesting alternative to study the structure and function of the normal and diseased retina in a human-like rodent model of retinal function.

The sand rat, Psammomys obesus, develops type 2 diabetic retinopathy similar to humans.

PURPOSE: Diabetic retinopathy (DR) is a leading cause of blindness, yet pertinent animal models are uncommon. The sand rat (Psammomys obesus), exhibiting diet-induced metabolic syndrome, might constitute a relevant model. METHODS: Adult P. obesus (n = 39) were maintained in captivity for 4 to 7 months and fed either vegetation-based diets (n = 13) or standard rat chow (n = 26). Although plant-fed animals exhibited uniform body weight and blood glucose levels over time, nearly 60% of rat chow-raised animals developed diabetes-like symptoms (test group). Animals were killed, and their eyes and vitreous were processed for immunochemistry. RESULTS: Compared with plant-fed animals, diabetic animals showed many abnormal vascular features, including vasodilation, tortuosity, and pericyte loss within the blood vessels, hyperproteinemia and elevated ratios of proangiogenic and antiangiogenic growth factors in the vitreous, and blood-retinal barrier breakdown. Furthermore, there were statistically significant decreases in retinal cell layer thicknesses and densities, accompanied by profound alterations in glia (downregulation of glutamine synthetase, glutamate-aspartate transporter, upregulation of glial fibrillar acidic protein) and many neurons (reduced expression of protein kinase Cα and Cξ in bipolar cells, axonal degeneration in ganglion cells). Cone photoreceptors were particularly affected, with reduced expression of short- and mid-/long-wavelength opsins. Hypercaloric diet nondiabetic animals showed intermediate values. CONCLUSIONS: Simple dietary modulation of P. obesus induces a rapid and severe phenotype closely resembling human type 2 DR. This species presents a valuable novel experimental model for probing the neural (especially cone photoreceptor) pathogenic modifications that are difficult to study in humans and for screening therapeutic strategies.