Spraque-Dawley Rats Research Articles

Ameliorative effect of ferulic acid on gentamicininduced nephrotoxicity in a rat model; role of antioxidant effects

Introduction: The nephrotoxicity of gentamicin is thought to be a dangerous side effect in the use of this drug caused by the formation of oxidative stress and the production of reactive oxygen species (ROS) and nitrogen species. Antioxidant agents play important roles in reducing oxidative stress. Objectives: In this study, the antioxidant role of ferulic acid has been studied in nephrotoxicity caused by gentamicin. Materials and Methods: In this experimental study, 50 Spraque-Dawley rats were randomly divided into 5 groups. The first group was considered as the control group and other groups received different doses of ferulic acid + 80 mg/kg gentamycin for 8 days by intraperitoneally injection. After the treatment, blood samples were prepared from animals. Then, the right and left kidneys were removed, paraffin blocks prepared, and the rest of the tissues were lysed. Three samples were used to evaluate serum creatinine and urea, as well as urine creatinine, histopathologic status and oxidative stress factors levels, respectively. To compare the results of different groups, Mann-Whitney U test was used. Results: Ferulic acid treatment decreased tissue malondialdehyde (MDA), serum urea and creatinine, urine albumin/creatinine ratio and neutrophil gelatinase-associated lipocalin (NGAL), and also increased superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). Ferulic acid reduced tubular necrosis and eosinophilic casts in gentamycin group induced nephrotoxicity. Conclusion: Ferulic acid can be effective in inhibiting gentamicin-induced nephrotoxicity.

The investigation of effect of alpha lipoic acid against damage on neonatal rat lung to maternal tobacco smoke exposure.

This study was carried out to determine the changes in the lungs of the rat pups exposed to tobacco smoke during pregnancy period and to investigate the protective effects of alpha lipoic acid, which is administered during pregnancy, on these changes. Spraque-Dawley female rats were divided into four groups: control, tobacco smoke (TS), tobacco smoke + alpha lipoic acid (TS + ALA) and alpha lipoic acid (ALA). The rats in control group were untreated. Rats were exposed to TS twice a day for one hour starting from eight weeks before mating and during pregnancy. 20 mg / kg of ALA was administered to rats. On 7th and 21st days 7 of the pups from each group were decapitated. Histological, morphometric, biochemical and quantitative real-time RT-PCR analyzes were performed. Histopathological and biochemical changes were observed in TS group. While a significant decrease was observed both in SP-A and VEGF immunoreactivities and mRNA levels, caspase-3 immunoreactivity and TUNEL positive cells were increased in TS group. It is suggested that prenatal TS exposure leads to morphological and histopathological changes on lung development by causing oxidative damage in lungs of neonatal rats and the maternal use of ALA can provide a limited protective effect on the neonatal lung development against this oxidative stress originating from TS. Although pregnant women are increasingly aware on health risks of smoking, environmental tobacco smoke exposure is still a widespread problem. For this reason, it is thought that this damage can be partially reduced by some antioxidant supplements in pregnancy.

Prenatal Dönemde 900Mhz Elektromanyetik Alanın Sıçan Omurilik Dokusu Üzerine Etkilerinin Histopatolojik Olarak İncelenmesi

Objective: Technological devices, which are introduced into our daily lives and radiate increasingly more electromagnetic waves with a certain frequency, expose people to an electromagnetic field. It is also well known that electromagnetic fields caused by these devices have certain adverse effects on the embryonic and pubertal development, and cause pathological changes in the tissues. Pathological changes, which emerge as a result of the damages in the spinal tissue, may cause signal conduction problems in the brain, and peripheral nervous system. Therefore, in our study, we investigated with histopathological analysis techniques the changes in the spinal tissue of rats during the prenatal period that were exposed to an electromagnetic field frequency: 900MHz .Materials and Methods: Total 18 rats 6 pregnant Spraque-Dawley female rats and 12 baby rats delivered by these rats were included into our study. We divided the rats into two groups as electromagnetic field group and control group. The electromagnetic group consisted of 6 newborn rats, which were exposed to the electromagnetic field during the prenatal period. Pregnant rats in the electromagnetic field group were exposed to a magnetic field of 900MHz radio frequency with a digital signal generator ER device that was placed in the center of the cage for 24 hours and 20 days. Newborn rats were kept 60 days for the pubertal stage development, and then they were anesthetized.Results: We observed that the neuronal perikaryon and oligodendrocytes in the samples of the electromagnetic field group had pyknotic nuclear structures. We also determined that the Kaspaz-3 positive cells were increased in the neurons and oligodendrocytes in the gray matter of the spinal tissue samples in the electromagnetic field group compared to the control group p=0.0001, p

Protective effect of aqueous extracts from Canarium odontophyllum Miq. leaf on liver in streptozotocin-induced diabetic rats

The fruit of Canarium odontophyllum Miq. are a traditional delicacy in Borneo for its anti-aging benefit. This study evaluated the protective effect of C. odontophyllum leaf aqueous extract on the damaged liver in streptozotocin-induced diabetic rats. A total of 30 male Spraque-Dawley rats (150-250g) were randomly divided into three groups: control group, diabetic without treatment and diabetic treated with 300 mg/kg aqueous extract once a day for 28 days. The diabetic condition was induced by intravenous injection of 65 mg/kg streptozotocin (STZ). The blood was collected to assess the biochemical changes and the oxidative stress marker whereas the liver section was examined for morphological changes. Result showed that the level of blood aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in STZ-induced rats treated with C. odontophyllum were significantly reduced (p<0.05) compared to STZ group. Oxidative stress test showed lower level of malondealdehid (MDA) and protein carbonyl but significantly (p<0.05) higher activity of GSH, SOD and GPx compared to untreated diabetic group. Abnormal cells were not detected from the histological observation. These findings demonstrated that the aqueous extract of C. odontophyllum has the potential to provide protective effect against liver damage in diabetic rat.

Histopathologic evaluation of the effects of local simvastatin application and photobiomodulation by light-emitting diode on bone healing of rat calvarial defects

ABSTRACTThe purpose of this study was to evaluate the effect of photombiomodulation (PBM) and locally applied simvastatin on bone formation in critical size defects of the experimental rat model calvarium. A total of 28 Spraque-Dawley male rats, mean age of 18 weeks, were used. Bilateral 5 mm critical sized calvarial defects were created. Then 0.5 mg/mL simvastatin solution was inoculated into gelatin sponge and locally applied on one side. The other side served as control. Half of the animals were subjected to PBM treatment and the remaining half were left for spontaneous healing. The animals were sacrificed by guillotine at days 8 and 15. The specimens were histopathologically analysed. The histopathologic evaluation revealed that the new bone formation levels were significantly higher at the 15th day compared to the 8th day. The bone formation levels with PBM and simvastatin treatment either combined or applied individually were significantly higher than the control ones. PBM and local simvastatin applications had favourable effects on the early phase of new bone formation and reduced the bone healing period in the rat model. Further human trials must be performed for evaluation of the reliability of this protocol.

Asiatic acid prevents the quinolinic acid-induced oxidative stress and cognitive impairment.

Increased accumulation of endogenous neurotoxin quinolinic acid has been found in various neurodegenerative diseases. Oxidative stress caused by quinolinic acid is considered as imperative factor for its toxicity. Asiatic acid, a natural triterpene is widely studied for its various medicinal values. In the present study the effects of asiatic acid in preventing the cognitive impairment and oxidative stress caused by quinolinic acid was investigated. Male Spraque-Dawley rats were orally administered asiatic acid (30mg/kg/day) for 28days, while quinolinic acid toxicity-induced animals received quinolinic acid (1.5mmol/kg/day) from day 15 to day 28 for 14days. Asiatic acid administration prevented the loss of spatial memory caused due to quinolinic acid-induced toxicity as determined using the novel object location test. In addition, asiatic acid administration alleviated the deleterious effect of quinolinic acid in brain such as increased oxidative stress, decreased antioxidant status and mitochondrial oxidative phosphorylation dysfunction. These data demonstrate that asiatic acid through its potent antioxidant and cognition enhancement property prevented the neuronal impairments caused by quinolinic acid.

The effects of pioglitazone in cirrhotic rats with hepatopulmonary syndrome

BackgroundHepatopulmonary syndrome (HPS) is characterized by oxygen desaturation and increased intrapulmonary shunting formation in cirrhosis. Due to an unclarified mechanism, there is still no effective therapy except liver transplantation. Recent studies revealed that pulmonary angiogenesis may participate in pathogenesis, in which nitric oxide (NO) and vascular endothelial growth factor (VEGF) play roles. Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, exerts anti-angiogenesis effect. However, whether pioglitazone influences pulmonary angiogenesis, shunting and HPS remains unexplored. MethodsCirrhosis with HPS was induced in Spraque-Dawley rats with common bile duct ligation (CBDL). Pioglitazone (10 mg/kg/day, oral gavage) or vehicle was administered from 8th to 28th day post CBDL. On the 28th day, the mortality rate, hemodynamic parameters, concentrations of plasma glucose and liver biochemistry parameters, and arterial blood gas data were evaluated. Lungs were dissected for protein expression analyses. In another series, intrapulmonary shunting degree was determined by color microsphere method in paralleled groups. ResultsThe survival rates were similar in HPS rats with or without pioglitazone administration. Pioglitazone did not influence the hemodynamic parameters, glucose and liver biochemistry levels, oxygen saturation and alveolar arterial gradient, but significantly down-regulated pulmonary VEGF protein expression, endothelial NO synthase (eNOS) activation, and decreased intrapulmonary shunts. Pioglitazone significantly decreased intrapulmonary shunts as compared with the vehicle (18.1 ± 4.5 vs. 9.8 ± 3.6, p = 0.015). ConclusionPioglitazone down-regulated VEGF, eNOS and decreased intrapulmonary shunts without improving oxygenation. The current finding suggests a multifactorial mechanism of HPS that could not be successfully overcome merely by pioglitazone-induced anti-angiogenesis and shunting reduction.

Intraluminal spindle-shaped-head suture induced occlusion of middle cerebral artery in the rats

Objective: This study aimed to introduce a modified animal model of middle cerebral arterial occlusion (MCAO) through placement of intraluminal spindle-shaped head suture by comparing the traditional MCAO model. Methods: A total of 60 male Spraque-Dawley (SD) rats were divided into two groups and MCAO was induced using spindle-shaped head suture or round head suture. The mortality, infarct volume, neurological function, success rate of the surgery, and stability of modeling were examined to evaluate the effectiveness of this model. Results: Our results showed the success rate was 90.0% in spindle-shaped head group and 83.3% in round head group showing no significant difference; spindle-shaped head achieved a better establishment of MCAO model as shown in neurological examination. The infarct volume was 31.99 ± 5.44% in spindle-shaped head group and was significantly higher than in round head group (24.59 ± 7.17%; p < 0.05), and the coefficient of variation of infarct volume in spindle-shaped head group was lower than in round head group. Conclusion: Our findings indicate that the modified suture induces a more reproducible and stable ischemic stroke following MCAO in SD rats.

SYSTEMATIC ASSESSMENT OF MINIMALLY-INVASIVE STRATEGIES FOR LUNG-TARGETED DELIVERY OF MICRORNA MIMICS IN RATS

MicroRNAs (miRNA) are key regulators of gene expression that have been causally implicated in the pathobiology of many different diseases. There is increasing interest in using synthetic miRNA mimics in vivo as potential therapeutic agents for pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. To assess the relative merits of four commonly used minimally-invasive strategies for lung-targeted administration of miRNA mimics in rats. A synthetic miRNA mimic with no mammalian homologue (cel-miR-39-3p; 0.5 nmol in 50 μL invivofectamine/PBS vehicle) was delivered to male Spraque-Dawley rats using 5 different strategies (n=3 rats/method). These included intratracheal liquid instillation (IT-L), intratracheal aerosolization (IT-A), intranasal liquid instillation (IN-L), intranasal aerosolization (IN-A) and intravenous (IV; via jugular vein) delivery. Relative levels of cel-miR-39 were quantified by RT-qPCR to assess pulmonary yield and distribution, persistence over time, and tissue-specificity. At 2 h post delivery, the highest levels of cel-miR-39 were achieved in the lungs after delivery by IT-L (mean ± SD; 9.4 ± 4.5, 2-ΔCq expression units). Expression levels progressively fell with delivery by IN-L (0.9 ± 1.6), IV (0.07 ± 0.02), IN-A (0.04 ± 0.04), and IT-A (0.0008 ± 0.0007). The pulmonary distribution of cel-miR-39 was generally comparable between delivery methods, with similar levels in both right and left lung lobes, and evidence of penetration to distal regions. Cel-miR-39 remained detectable in lung tissue 24 h post delivery, but levels were 10-100 fold lower. All methods, with the exception of IV delivery, showed lung-selective targeting, with cel-miR-39 levels 10-100 fold lower in the heart and 100-10000 fold lower in the liver. MicroRNA uptake in the lungs differed markedly by up to 4 orders of magnitude depending of the method of administration, suggesting that the choice of delivery strategy could have a significant impact on potential therapeutic outcomes in preclinical investigations of miRNA-based drug candidates.

Ascorbate lacks significant influence in rats with bile duct ligation-induced liver injury

BackgroundLiver inflammation may induce fibrogenesis, cirrhosis and portal hypertension. Liver cirrhosis is characterized by increased intrahepatic resistance and enhanced vasoconstrictive response. The splanchnic vasodilatation, angiogenesis and portosystemic collaterals formation further bring about lethal complications. Ascorbate is a potent antioxidant with anti-inflammation, anti-fibrosis, and anti-angiogenesis effects. However, the relevant influences in chronic liver injury have not been sufficiently explored. MethodsChronic liver injury was induced in Spraque-Dawley rats with common bile duct ligation (BDL). Ascorbate (250 mg/kg/day, oral gavage) or vehicle was administered starting on the 1st day after operation. On the 8th (hepatitis) and 29th (cirrhosis) day, serum biochemistry parameters, hepatic concentrations of lipid peroxidation-related substances, protein expressions of α-SMA, TGF-β, iNOS, eNOS, p-eNOS-Ser1177, p-eNOS-Thr496, VEGF, VEGFR2, p-VEGFR2, and liver histology were evaluated. In three series of paralleled groups, rats treated with 28-day ascorbate or vehicle received hemodynamic measurements, hepatic and collateral vasoresponsiveness perfusion experiments, mesenteric CD31 immunofluorescence staining, and Western blot analyses of mesenteric VEGF, VEGFR2, pVEGFR2, PDGF, PDGFβ, COX1, COX2, eNOS, p-eNOS-Thr495, p-eNOS-Ser1177 protein expressions. In another series, the severity of portosystemic shunting was evaluated. ResultsAscorbate did not influence hepatitis, oxidative stress, fibrosis, and hemodynamic parameters in BDL rats. The intrahepatic and collateral vasoresponsiveness were not affected, either from direct incubation or acute treatment with ascorbate. Furthermore, the mesenteric angiogenesis and severity of shunting were not influenced. ConclusionThe oxidative stress, fibrosis, hemodynamic derangements, angiogenesis and vascular functional changes in BDL-induced chronic liver injury may be too overwhelming to be modulated by ascorbate.

DARAPLADIB INHIBIT ADHESION MOLECULE EXPRESSION IN AORTA AT EARLY STAGES OF ATHEROSCLEROSIS USING SPRAGUE-DAWLEY TYPE 2 DIABETES MELLITUS MODEL

Objective: Hyperglycemia and hyperlipidemia in diabetes mellitus (DM) can lead an atherosclerosis. The increase of low-density lipoprotein level in DM and atherosclerosis is correlated with lipoprotein-associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids. LysoPC regulated inflammation mediators, include cytokines, adhesion molecules (such as vascular cell adhesion molecule-1 [VCAM-1] and intercellular adhesion molecules-1 [ICAM-1]), and monocyte chemoattractant protein-1 (MCP-1) chemotactic. Darapladib is known as a Lp-PLA2 specific inhibitor. It is also considered to be an atherosclerosis treatment. The aim of this study is to know darapladib effect on VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using Sprague-Dawley Type 2 DM (T2DM) model.Methods: About 30 Spraque-Dawley rats are divided into three main groups: Normal, T2DM, and T2DM with darapladib administration group. Each group consists of 2 serials treatment time: 8 and 16 weeks treatment group. Fasting blood glucose, resistance insulin, and lipid profile were measured and analyzed to ensure T2DM model. VCAM-1 and ICAM-1 expression were measured using double staining immunofluorescence. Each data were analyzed using one-way ANOVA.Results: There is a significant difference in VCAM-1 expression in T2DM group (8 and 16 weeks), with p=0.011 and 0.034 (p&lt;0.05), respectively. Mean while, a significant difference for ICAM-1 only showed in 8 weeks T2DM group with p=0.03 (p&lt;0.05). Moreover, there is a decreasing trend in 16 weeks T2DM group.Conclusion: Our results showed that darapladib can decrease VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using Sprague- Dawley T2DM model. This showed another evidence of darapladib as atherosclerosis treatment.

Severe bilateral ischemic-reperfusion renal injury: hyperacute and acute changes in apparent diffusion coefficient, T1, and T2 mapping with immunohistochemical correlations

The aim of this study was to investigate the hyperacute and acute changes in apparent diffusion coefficient (ADC), T1, and T2 mapping in rat kidneys after severe bilateral renal ischemic-reperfusion injury (IRI). After baseline MRI, 24 Spraque-Dawley rats with renal IRI were divided equally as group 1 (post-IRI MRI at 6 hours, days 1, 3, and 7) and groups 2, 3, and 4 (post-IRI MRI at 6 hours; 6 hours and day 1; 6 hours, days 1 and 3, respectively), while six other rats without IRI (group 5) were used as sham control. ADC, T1, and T2 values of the cortex and outer and inner stripes of outer medulla (OSOM and ISOM), and immunohistochemical studies assessing monocyte chemoattractant protein-1 (MCP-1), CD68+ cells, tubular cast formation, and collagen deposition in three zones at different time points were evaluated. Significantly reduced ADCs in OSOM and ISOM are noninvasive biomarkers denoting hyperacute damages after IRI. Linear regression analysis revealed a significant inverse correlation between 6-hour/baseline ADC ratios and MCP-1 staining (P < 0.001, r2 = 0.738). ADC, T1, and T2 values are useful for assessing variable IRI changes in different layers depending on underlying microstructural and histopathological changes at different time points.

Comparison of the impact of epigallocatechin gallate and ellagic acid in an experimental cataract model induced by sodium selenite.

To compare the potential protective effects of epi-gallocatechin gallate (EGCG) and ellagic acid (EA) in an experimental cataract model. Twenty-eight Spraque-Dawley rat pups were assigned into four groups. All the rats, except for those in the control group, were injected subcutaneously sodium selenite to induce experimental cataract on the postpartum ninth day, and between 10th and 14th days. Rats in the sham, EGCG, and EA groups were intraperitoneally administered 50 mg/(kg·d) saline solution, 50 mg/(kg·d) EGCG and 200 mg/(kg·d) EA, respectively. The reduced glutathione (GSH) and malondialdehyde (MDA) levels, total antioxidant status (TAS) and total oxidant status (TOS) in lens supernatants were measured. The mean cataract gradings in EGCG and EA groups were found to be significantly lower than that in sham group (P<0.001). The mean GSH levels and TASs in EGCG and EA groups were significantly higher than that in sham group while mean MDA levels and TOSs in EGCG and EA groups were significantly lower than that in the sham group (P<0.001). EGCG and EA have protective effects on cataract development via the inhibition of oxidative stress.

Effects of metals cadmium and chromium alone and in combination on the liver and kidney tissue of male Spraque-Dawley rats: An ultrastructural and electron-energy-loss spectroscopy investigation.

Heavy metal pollution has increased in the last decades. Water sources are contaminated and human exposure is often long term exposure to variable amounts of different metals. In this study, male Sprague-Dawley rats were exposed via oral gavage for 28days to cadmium (Cd) and chromium (Cr), alone and in combination at concentrations 1000 times the human World Health Organization's acceptable water limits. Rat equivalent dosages were used. Blood markers of liver and kidney function were measured, changes to cellular morphology was determined with transmission electron microscopy and the intracellular metal localisation was determined with the electron energy-loss spectroscopy and energy filtered transmission electron microscopy analysis. Both Cd and Cr caused changes to the nuclear and mitochondrial membranes and irregular chromatin condensation of hepatocytes. Cr exposure caused dilation of the rough endoplasmic reticulum (rER). The combination caused nuclear and mitochondrial membrane damage as well as irregular chromatin condensation. In the kidney tissue, Cd caused irregular chromatin condensation in the cells of the proximal convoluted tubule (PCT). Cr caused changes to the outer nuclear and mitochondrial membrane and chromatin structure. The combination group caused membrane damage, irregular chromatin condensation and rER changes in the PCT. All the metal groups showed damage to the endothelial cells and pedicles, but not to the mesangial cells. Cd and Cr bio-accumulation was observed in the nucleus, mitochondria and rER of the liver and kidney and therefore are responsible for the cellular observed damage that can cause functional changes to the tissues and organs.

Gelam honey increases antioxidant enzyme activity in young rat cardiac mitochondria

Objective: The aim of this study is to determine the effect of gelam honey on antioxidant enzyme activity in cardiac mitochondria of young and aged rats. Methods: Twenty-four male Spraque-Dawley rats were divided into young (2 months) and aged (19 months) groups. Each group was further divided into control (fed with plain water) and supplemented with 2.5 g/kg body weight of gelam honey for 8 months. Results: Gelam honey increases cardiac manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx) activities in young. Malondialdehyde (MDA) level was reduced in gelam honey supplemented young group. Gelam honey increases cytochrome oxidase activity in the young group compared to control. Conclusions: Gelam honey reduces the oxidative damage and increase mitochondrial function by increasing antioxidant enzymes and cytochrome oxidase activity in the young group.

Comparison of Systemic and Topical Hypericum Perforatum on Diabetic Surgical Wounds

ABSTRACTBackground: Surgical wounds in diabetic patients still remain a problem till the present day. As a common plant found around the world, Hypericum perforatum L. (Hypericaceae) is traditionally prepared as an oily extract and used as a folk remedy for various diseases such as wounds, burns, cuts, etc. This study aims to evaluate the effect of St. John's wort (Hypericum perforatum) on problematic wounds while comparing oral and topical applications. Methods: Incisional and excisional wound models were made on the dorsal regions of 54 diabetic Spraque–Dawley rats. The rats were divided into the following six groups (n = 9): Group 1: control, Group 2: diabetic, Group 3: diabetic oral Hypericum perforatum, Group 4: diabetic topical Hypericum perforatum, Group 5: diabetic oral olive oil, and Group 6: diabetic topical olive oil. Results: Groups 3 and 4 had significantly higher tensile strength, tissue hydroxyproline concentration, and collagen density compared with Group 2. Inflammatory cell density and collagen density on day 3 were significantly higher in Groups 3 and 6 compared with Group 2. On day 21, Groups 3 and 6 had significantly higher fibroblastic activity compared with Group 2. Conclusions: This study has proved that oral St. John's wort has more positive effects on problematic wounds compared with topical St. John's wort and olive oil, which is a vehicle. Hypericum perforatum results with faster inflammatory response and better healing. These results could be an addition to literature about the clinical usage of Hypericum perforatum on diabetic wounds.

Protective effect of CDP-choline on hypotension and tissue injury in septic shock model

CDP-choline is an endogen molecule and also a drug that is used in several trauma and ischemic conditions. It has been demonstrated that it improves the hemodynamic parameters in different shock models and prevents tissue damage in rats. The current study tested the effect of CDP-choline on hypotension, inflammation and tissue injury induced by septic shock model in rats. Twenty-four adult, male Spraque-Dawley rats, weighing 250-300 g were used. Septic shock was induced by cecal ligation-incision (CLI). CDP-choline (100 mg/kg) injected intravenously (i.v.) at the 180th minute of the experiment. The animals were observed for 180 minutes after the injection, then blood and tissue samples were obtained for cytokine measurements and histological examinations, respectively. The cecal ligation-incision decreased arterial pressure and increased heart rate. Intravenous injection of CDP-choline reversed hypotension and increased arterial pressure up to control levels within the first 60 minutes without changing the increase in heart rate. The effect lasted for 3 hours. CDP-choline attenuated the increases in TNF-α, IL-1β and IL-6 levels in septic shock. Moreover, the drug exerted protective effects for the injury induced by septic shock in lungs, liver and kidney tissues; whereas this effect was not present on spleen. In conclusion, the present data suggested that intravenous CDP-choline administration can improve the deteriorations in hemodynamic and inflammatory parameters and can prevent the tissue injury in septic shock-induced by CLI in rats

Short-term Effects of Date Palm Extract (Phoenix dactylifera) on Ischemia/Reperfusion Injury Induced by Testicular Torsion/Detorsion in Rats.

Background:Antioxidants are potent scavengers of free radicals and have beneficial effects on human health.Objective:The aim of this study was to investigate the potential protective antioxidant activity of the edible portion of date fruit extract in an experimental testicular torsion/detorsion (T/D) model in rats.Materials and Methods:To investigate the potential protective effects of date palm (DP), 30 male Spraque-Dawley rats were divided into three groups: sham-operated, T/D, and T/D + DP-treated (500 mg/kg, PO) groups. Testicular ischemia was induced via keeping the left testis under 720° clockwise torsion for 2 h (h), afterward, detorsion was performed. All rats were sacrificed 4 h after detorsion. Serum malondialdehyde (MDA) concentration, total oxidative status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and histopathological damage score were evaluated.Results:Serum MDA, TOS, and OSI levels rose significantly in the T/D group. These values were lower in the T/D + DP group. TAS values decreased significantly in T/D group and rose in T/D + DP group. Severe injury was seen in the twisted testes of T/D group. In contrast, ipsilateral-twisted testicular tissue in the DP-treated group showed moderate-to-mild changes. Contralateral testicular tissue in the T/D group had a mild-to-moderate tissue injury; meanwhile, treated group revealed normal-to-mild changes. Spermatogenesis was significantly improved in DP-treated group when compared with the T/D group.Conclusion:The findings suggest a possible protective effect of DP against testicular oxidative damage induced by T/D; however, more detailed studies are warranted.SUMMARYGiven the presence of several phenolic compounds possessing high antioxidant activity in DP, it could potentially be used to reduce testis ischemia/reperfusion-induced damage.Abbreviations Used: TAS: Total antioxidant status,TOS: Total oxidative status; OSI: Oxidative stress index; MDA: Malondialdehyde; C: Congestion; H: Hemorrhage, E: Edema; SG: Sloughed germinal cells; SA: Spermatogenesis arrest; STD: Seminiferous tubules disorganization; STA: Seminiferous tubules atrophy; G: Giant cells; T/D: Torsion/detorsion; DP: Date palm

Localization and quantification of dystrophin in epileptic rats

Aim: In Duchenne muscular dystrophy (DMD) populations, a higher prevalence of epilepsy has been found compared with control groups. We hypothesized that epilepsy/seizures causes loss of dystrophin in the brain. Our aim was to localize dystrophin in cerebellum and hippocampus and to develop a reliable method for quantification of dystrophin. Methods: Male adult Spraque-Dawley rats were used in a amygdala kindled model (N=24). Cerebellar and hippocampal tissue were stained immunohistochemically with anti-dystrophin, anti-calbindin, anti-GFAP and Hoechst. Anti-NeuN was only applied in hippocampal tissue. Under fluorescent microscope, pictures were taken for quantification in ImageJ. Results: Glia cells and Purkinje cells colocalized with dystrophin, however, hippocampal neuronal cells did not show a colocalization with dystrophin. Statistical analysis of the quantification of dystrophin around the Purkinje neuron, showed a high intra-observer correlation (Mean grey value: Pearson correlation (r=1,000, P&lt;0,0001) and ICC (r=1,000, P&lt;0,0001); Intensity density: Pearson correlation (r=0,986, P&lt;0,000) and ICC (r=0,984, P&lt;0,0001)). Conclusion: Dystrophin is ubiquitously expressed in the cerebellum and hippocampus, but the exact distribution of the dystrophin isoforms in these areas are not clear yet. We have developed a reliable quantification method of dystrophin around the cerebellar Purkinje cells, but not for glia cells and hippocampal neurons. Future studies should therefore not only be aimed at the distribution of the dystrophin isoforms, but also at the quantification of glia cells and hippocampal neurons.

The protective effect of the proteasome inhibitor bortezomib on the uterus of ovariectomized rats

Bortezomib (BORT) is an anti-tumour agent that inhibits proteasome, which is responsible for the degradation of many intracellular proteins. Although some side-effects and chemotherapeutic effects of BORT are known, there has not been enough research regarding its effects on different tissues of proteasome inhibition in the senile period (post-menopausal). The aim of this study was to investigate the safety of using BORT during the post-menopausal period. The post-menopausal effects of BORT were investigated on ovariectomized (OVX) Spraque-Dawley rats. The female rats were separated into three groups: control, ovariectomized (OVX), and OVX + BORT. OVX and OVX + BORT groups consisted of six rats in each. BORT was administered intraperitoneally in a dosage of 0.2 mg/kg two days a week for four weeks after OVX. The uteri of the rats were investigated using morphometrical, histopathological, and immunohistopathological methods. A striking atrophy in the endometrium and myometrium was observed due to an estrogen deficiency in the OVX group. The partial protective effect of BORT administration was observed morphometrically and histopathologically. In immunohistochemical research, cytoplasmic NF-&#x03BA;B activity was observed in the presence of proteasome inhibition in the endometrium. In light of these findings, the limited protective effects of post-menopausal BORT administration are worth mentioning.