Stress In Sprague-Dawley Rats Research Articles

IRE1α/NOX4 signaling pathway mediates ROS-dependent activation of hepatic stellate cells in NaAsO2 -induced liver fibrosis.

Liver fibrosis is a severe health problem worldwide, and it is characterized by the activation of hepatic stellate cells (HSCs) and excessive deposition of collagen. Prolonged arsenic exposure can induce HSCs activation and liver fibrosis. In the present study, the results showed that chronic NaAsO2 ingestion could result in liver fibrosis and oxidative stress in Sprague-Dawley rats, along with representative collagen deposition and HSCs activation. In addition, the inositol-requiring enzyme 1α (IRE1α)-endoplasmic reticulum (ER)-stress pathway was activated, and the activity of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) was upregulated in rat livers. Simultaneously, the excessive production of reactive oxygen species (ROS) could induce HSCs activation, and NOX4 played an important role in generating ROS in vitro. Moreover, ER stress occurred with HSCs activation at the same time under NaAsO2 exposure, and during ER stress, the IRE1α pathway was responsible for NOX4 activation. Therefore, inhibition of IRE1α activation could attenuate the HSCs activation induced by NaAsO2 . In conclusion, the present study manifested that inorganic arsenic exposure could activate HSCs through IRE1α/NOX4-mediated ROS generation.

The experimental application of steam explosion-pre-treated flaxseed meal with hypoglycaemic and lipid-lowering functions in rats on a high-fat-sugar diet

With the increase in populations with suboptimal health and chronic diseases, consumer demands for health foods, especially food products with health functions. The flaxseed was a complex mixture mainly consisting of flaxseed oil, flaxseed protein, dietary fibre (including cellulose and flaxseed gum), carbohydrates and secoisolariciresinol diglucoside (SDG). To investigate the effects of expanded flaxseed meal (EFM) intervention on the hypoglycaemic and lipid-lowering functions of rats on a high-fat, high-sugar (HFHS) diet, EFM was fed to six groups (z = 8) of Sprague–Dawley (SD) rats: normal control, HFHS model, positive treatment control, and low-, medium-, and high-dose EFM (5%, 10% and 20% mass fraction EFM, respectively) groups. The results (8 weeks later) were as follows: (1) medium- and high-dose EFM achieved similar inhibitive effects on blood glucose levels compared with positive treatment (5.94±0.32 mmol/L); (2) all EFM doses significantly reduced total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in the blood plasma of SD rats and (3) EFM significantly increased glutathione peroxidase, superoxide dismutase and catalase activities, increased glutathione levels, and reduced the malondialdehyde content in the plasma of SD rats (P < 0.05). Therefore, EFM mitigated the adverse effects produced by HFHS diet on physiological functions, effectively regulated blood glucose and lipid metabolism, enhanced plasma antioxidant capacity and alleviated oxidative stress in SD rats with a certain dose–effect relationship among the EFM dose groups. Hepatic histological morphologies indicated that EFM also improved the size and density of lipid droplets in the liver of the rats and inhibited the onset of fatty liver. These results suggest that EFM is a potentially useful raw material in the development of blood glucose and lipid-lowering food products.

Effect of feeding coconut sugar-mix coffee rich in antioxidants on blood pressure, serum SOD and MDA of sprague dawley rats

High exposure to cigarette smoke triggers oxidative stress, thereby the intake of foods rich in antioxidants is needed. Coconut sugar-mix coffee enriched with antioxidants from red palm oil is one of the alternatives to increase the supply of antioxidants. This study aimed to determine the effects of feeding coconut sugar mixed coffee rich in antioxidant (CMCRA) on blood pressure, serum SOD and MDA of Sprague Dawley rats. Six groups of rats (n = 6) received the following treatments: one group of rats were given 0.45 g/day of the CMCRA without exposure to cigarette smoke (positive control/P1) while five groups of rats were exposed to cigarette smoke from two cigarettes per day during the study period and given distilled water (negative control/P2), 0.45 g/day of CMCRA (P3), 0.90 g/day of the CMCRA (P4), 1.35 g/day of the CMCRA (P5), and 0.45/day of cane sugar mixed coffee (P6). The observations were conducted on body weight, blood pressure, serum SOD levels, and serum MDA levels. The results of the study showed that the delta increase in blood pressure in the CMCRA groups was lower (5.8–28.6 mmHg) than the cane sugar coffee group (79.2 mmHg) or the negative control group (103.6 mmHg). The decrease in serum SOD levels in the tested-coffee groups (6.75– 44.62%) was lower than the market-sold coffee group (45.97%) or the negative control group (60.44%). The delta increase in serum MDA levels was lower in the tested-coffee groups (0.51– 5.73 nmol/mL) compared to the cane sugar coffee group (6.69 nmol/mL) or the negative control/distilled water group (8.28 nmol/mL). The coffee drinks enriched with antioxidants from red palm oil have the potential to suppress oxidative stress in Sprague-Dawley rats exposed to cigarette smoke.

Red orange and lemon extract prevents the renal toxicity induced by ochratoxin A in rats.

In this work, we investigated the effects of red orange and lemon extract (RLE) on ochratoxin A (OTA)-induced nephrotoxicity. In particular, we analyzed the change in renal function and oxidative stress in Sprague-Dawley rats treated with OTA (0.5 mg/kg body weight, b.w.) and with RLE (90 mg/kg b.w.) by oral administration. After OTA treatment, we found alterations of biochemical and oxidative stress parameters in the kidney, related to a severe decrease of glomerular filtration rate. The RLE treatment normalized the activity of antioxidant enzymes and prevented the glomerular hyperfiltration. Histopathological examinations revealed glomerular damages and kidney cortex fibrosis in OTA-rats, while we observed less severe fibrosis in OTA plus RLE group. Then, we demonstrated that oxidative stress could be the cause of OTA renal injury and that RLE reduces this effect.

Free Radical Scavenging Activity of Aerial Parts of <i>Artemisia pallens</i> in Mediating Hepatoprotective Activity of RIF+INH Intoxicated Rats

To investigate the free radical scavenging & hepatoprotective activity of phenolic rich fraction of Artemisia pallens on RIF+INH induced oxidative stress in Sprague dawley rats. Free radical scavenging and hepatoprotective activity was evaluated by using DPPH, Nitric oxide, Superoxide radical and Hydroxyl radical assay models and induced RIF+INH intoxicated rats. The total phenolic content was found to be 312.60 μg gallic acid equivalents (GAE)/gm of dry extract. The total flavonoid content was found to be 322.20 μg rutin equivalents (RUE)/gm of dry extract. In the current study, free radical scavenging activity was evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide, superoxide radical and hydroxyl radical scavenging activity were found to be (42.25 ± 0.95) and (09.16 ± 1.62) μg/ml, (101.62 ± 1.64) and (32.41 ± 1.24) μg/ml, (72.62 ± 1.86) and (10.28 ± 1.96) μg/ml, (33.82 ± 1.12) and (12.82 ± 1.86) μg/ml, respectively. There was also a dose dependent increase in reductive ability of Artemisia pallens extract with increase in concentration and were further investigated in invivo hepatoprotective activity experiment against toxicity induced by RIF+INH. The free radical scavenging and hepatoprotective activity may be attributed to the presence of phenolic compounds and histology of the liver section of the animals treated with the extracts showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration, which further evidenced the hepatoprotective activity of Artemisia pallens.

Metabolome and microbiome profiling of a stress-sensitive rat model of gut-brain axis dysfunction

Stress negatively impacts gut and brain health. Individual differences in response to stress have been linked to genetic and environmental factors and more recently, a role for the gut microbiota in the regulation of stress-related changes has been demonstrated. However, the mechanisms by which these factors influence each other are poorly understood, and there are currently no established robust biomarkers of stress susceptibility. To determine the metabolic and microbial signatures underpinning physiological stress responses, we compared stress-sensitive Wistar Kyoto (WKY) rats to the normo-anxious Sprague Dawley (SD) strain. Here we report that acute stress-induced strain-specific changes in brain lipid metabolites were a prominent feature in WKY rats. The relative abundance of Lactococcus correlated with the relative proportions of many brain lipids. In contrast, plasma lipids were significantly elevated in response to stress in SD rats, but not in WKY rats. Supporting these findings, we found that the greatest difference between the SD and WKY microbiomes were the predicted relative abundance of microbial genes involved in lipid and energy metabolism. Our results provide potential insights for developing novel biomarkers of stress vulnerability, some of which appear genotype specific.

Efecto protector de la vitamina C sobre el estrés oxidativo y daño al ADN en ratas con diabetes mellitus

<p>La diabetes mellitas (DM) es una enfermedad metabólica de origen endocrino, cuya principal característica bioquímica es la hiperglucemia crónica. Desencadena procesos bioquímicos graves para el organismo como el estrés oxidativo (EO). El objetivo de este estudio fue evaluar el efecto protector de la vitamina C (VitC) sobre el EO en ratas Sprague-Dawley con DM inducida por Streptozotocina (STZ). Se utilizaron 16 ratas (100 ± 20 g), divididas en 4 grupos: 1) control, 2) STZ (diabéticas), 3) VitC + STZ, 4) VitC. En homogenizado de hígado se determinó la concentración de malondiahaldehido, dienos conjugados y proteínas totales. Por otra parte se determinaron las actividades de superóxido dismutasa y catalasa. También se midió el daño al ADN hepático por ensayo cometa. Los resultados se analizaron estadísticamente mediante programa SPSS versión 17.0 para Windows. Se aplicó un Anova y una prueba de comparación múltiple DMS (p<0,05). Se pudo evidenciar que en el grupo de animales tratados con VitC disminuyeron los niveles de glucosa y la generación de EO; también hubo menor daño del ADN por radicales libres. Estos datos permiten inferir que la VitC ejerce una efectiva acción antioxidante y protectora del hígado ante la permanente producción de radicales libres; además de ser efectiva en la reparación y conservación del ADN.</p><p> </p>

Red Rosella (Hibiscus sabdariffa Linn.) Petal Brew is Able to Reduce the Sprague Dawley MDA Rate in Rats Exposed to Waste Cooking Oil

Food and snacks sold are usually fried using oil that has been used for frying repeatedly. Oil that is repeatedly used for frying is often called waste cooking oil. Waste cooking oil is a source of exogenous free radicals that can trigger oxidative stress. To prevent this, sufficient antioxidant intake is needed. One source of antioxidants is red rosella. The purpose of this study was to analyze the effect of giving red rosella petals on the conditions of oxidative stress in Sprague dawley rats exposed to waste cooking oil through MDA testing. The research method used was Completely Randomized Design (CRD). The sample consisted of 24 male rats which were randomly selected and divided into 4 groups: negative control (no treatment), positive control (administered with waste cooking oil of 8.92 meq/kg as much as 2 ml/kgBW), treatment 1 (administered with waste cooking oil of 8.92 meq/kg as much as 2 ml/kgBW and red rosella petal brew dosed of 540 mg/kgBW, and treatment 2 (administered with waste cooking oil of 8.92 meq/kg as much as 2 ml/kgBW and red rosella petals brew dosed of 810 mg/kgBW). The results of the one way ANOVA analysis (a=1%) and the Tukey HSD test showed the p value of MDA=0.00, indicating that all treatments had significant effect. In further tests, it was found that all treatments contained differences in MDA values. The best value in the treatment was by giving a dose of 810 mg/kgBW (serum MDA of 2.22 nmol/ml). It can be concluded that the administration of red rosella petal in doses of 540 mg/kgBW (EC50=407.52 ppm) and 810 mg/kgBW (EC50=247.82 ppm) can improve the oxidative stress of Sprague dawley rats.Food and snacks sold are usually fried using oil that has been used for frying repeatedly. Oil that is repeatedly used for frying is often called waste cooking oil. Waste cooking oil is a source of exogenous free radicals that can trigger oxidative stress. To prevent this, sufficient antioxidant intake is needed. One source of antioxidants is red rosella. The purpose of this study was to analyze the effect of giving red rosella petals on the conditions of oxidative stress in Sprague dawley rats exposed to waste cooking oil through MDA testing. The research method used was Completely Randomized Design (CRD). The sample consisted of 24 male rats which were randomly selected and divided into 4 groups: negative control (no treatment), positive control (administered with waste cooking oil of 8.92 meq/kg as much as 2 ml/kgBW), treatment 1 (administered with waste cooking oil of 8.92 meq/kg as much as 2 ml/kgBW and red rosella petal brew dosed of 540 mg/kgBW, and treatment 2 (administered with waste cooking oil of 8.92 meq/kg as much as 2 ml/kgBW and red rosella petals brew dosed of 810 mg/kgBW). The results of the one way ANOVA analysis (a=1%) and the Tukey HSD test showed the p value of MDA=0.00, indicating that all treatments had significant effect. In further tests, it was found that all treatments contained differences in MDA values. The best value in the treatment was by giving a dose of 810 mg/kgBW (serum MDA of 2.22 nmol/ml). It can be concluded that the administration of red rosella petal in doses of 540 mg/kgBW (EC50=407.52 ppm) and 810 mg/kgBW (EC50=247.82 ppm) can improve the oxidative stress of Sprague dawley rats.

Novel mechanism within the paraventricular nucleus reduces both blood pressure and hypothalamic pituitary-adrenal axis responses to acute stress.

Macrophage migration inhibitory factor (MIF) counteracts pressor effects of angiotensin II (ANG II) in the paraventricular nucleus of the hypothalamus (PVN) in normotensive rats, but this mechanism is absent in spontaneously hypertensive rats (SHRs) due to a lack of MIF in PVN neurons. Since endogenous ANG II in the PVN modulates stress reactivity, we tested the hypothesis that replacement of MIF in PVN neurons would reduce baseline blood pressure and inhibit stress-induced increases in blood pressure and plasma corticosterone in adult male SHRs. Radiotelemetry transmitters were implanted to measure blood pressure, and then an adeno-associated viral vector expressing either enhanced green fluorescent protein (GFP) or MIF was injected bilaterally into the PVN. Cardiovascular responses to a 15-min water stress (1-cm deep, 25°C) and a 60-min restraint stress were evaluated 3-4 wk later. MIF treatment in the PVN attenuated average restraint-induced increases in blood pressure (37.4 ± 2.0 and 27.6 ± 3.5 mmHg in GFP and MIF groups, respectively, P < 0.05) and corticosterone (42 ± 2 and 36 ± 3 μg/dl in GFP and MIF groups, respectively, P < 0.05). MIF treatment in the PVN also reduced stress-induced elevations in the number of c-Fos-positive cells in the rostral ventrolateral medulla (71 ± 5 in GFP and 47 ± 5 in MIF SHRs, P < 0.01) and corticotropin-releasing factor mRNA expression in the PVN. However, MIF had no significant effects on the cardiovascular responses to water stress in SHRs or to either stress in Sprague-Dawley rats. Therefore, viral vector-mediated restoration of MIF in PVN neurons of SHRs attenuates blood pressure and hypothalamic pituitary adrenal axis responses to stress.

Prenatal stress and subsequent exposure to chronic mild stress in rats; interdependent effects on emotional behavior and the serotonergic system

Exposure to prenatal stress (PS) can predispose individuals to the development of psychopathology later in life. We examined the effects of unpredictable chronic mild stress (CMS) exposure during adolescence on a background of PS in male and female Sprague-Dawley rats. PS induced more anxiety-like behavior in the elevated zero maze in both sexes, an effect that was normalized by subsequent exposure to CMS. Moreover, PS was associated with increased depression-like behavior in the forced swim test in males only. Conversely, sucrose intake was increased in PS males, whilst being decreased in females when consecutively exposed to PS and CMS. Hypothalamo–pituitary–adrenal (HPA) axis reactivity was affected in males only, with higher stress-induced plasma corticosterone levels after PS. Markedly, CMS normalized the effects of PS on elevated zero maze behavior as well as basal and stress-induced plasma corticosterone secretion. At the neurochemical level, both PS and CMS induced various sex-specific alterations in serotonin (5-HT) and tryptophan hydroxylase 2 (TPH2) immunoreactivity in the dorsal raphe nucleus, hippocampus and prefrontal cortex with, in line with the behavioral observations, more profound effects in male offspring. In conclusion, these findings show that prenatal maternal stress in Sprague-Dawley rats induces various anxiety- and depression-related behavioral and neuroendocrine changes, as well as alterations in central 5-HT and TPH2 function, predominantly in male offspring. Moreover, CMS exposure partially normalized the effects of previous PS experience, suggesting that the outcome of developmental stress exposure largely depends on the environmental conditions later in life and vice versa.

Grape Powder Supplementation Prevents Oxidative Stress–Induced Anxiety-Like Behavior, Memory Impairment, and High Blood Pressure in Rats

We examined whether or not grape powder treatment ameliorates oxidative stress–induced anxiety-like behavior, memory impairment, and hypertension in rats. Oxidative stress in Sprague-Dawley rats was produced by using L-buthionine-(S,R)-sulfoximine (BSO). Four groups of rats were used: 1) control (C; injected with vehicle and provided with tap water), 2) grape powder–treated (GP; injected with vehicle and provided for 3 wk with 15 g/L grape powder dissolved in tap water), 3) BSO-treated [injected with BSO (300 mg/kg body weight), i.p. for 7 d and provided with tap water], and 4) BSO plus grape powder–treated (GP+BSO; injected with BSO and provided with grape powder–treated tap water). Anxiety-like behavior was significantly greater in BSO rats compared with C or GP rats (P < 0.05). Grape powder attenuated BSO-induced anxiety-like behavior in GP+BSO rats. BSO rats made significantly more errors in both short- and long-term memory tests compared with C or GP rats (P < 0.05), which was prevented in GP+BSO rats. Systolic and diastolic blood pressure was significantly greater in BSO rats compared with C or GP rats (P < 0.05), whereas grape powder prevented high blood pressure in GP+BSO rats. Furthermore, brain extracellular signal-regulated kinase-1/2 (ERK-1/2) was activated (P < 0.05), whereas levels of glyoxalase-1 (GLO-1), glutathione reductase-1 (GSR-1), calcium/calmodulin-dependent protein kinase type IV (CAMK-IV), cAMP response element–binding protein (CREB), and brain-derived neurotrophic factor (BDNF) were significantly less (P < 0.05) in BSO but not in GP+BSO rats compared with C or GP rats. We suggest that by regulating brain ERK-1/2, GLO-1, GSR-1, CAMK-IV, CREB, and BDNF levels, grape powder prevents oxidative stress–induced anxiety, memory impairment, and hypertension in rats.

Rosiglitazone attenuates casein-induced hepatic endoplasmic reticulum stress in Sprague-Dawley rats: a novel model of endoplasmic reticulum stress

The proteins found in cow milk have been reported to cause systemic inflammation. Endoplasmic reticulum (ER) stress is known to be involved in the development of several metabolic disorders including insulin resistance and non-alcoholic fatty liver disease. However, the effect of thiazolidinediones (TZDs) on ER stress is still controversial. This is why we want to investigate in this study whether casein, which is the major protein in cow's milk, induces ER stress in the liver and whether rosiglitazone can attenuate these changes. Nine-week-old male Sprague-Dawley (SD) rats were separated into three groups: (1) vehicle treated; (2) daily subcutaneous injections of 1 mL 10% casein; (3) daily subcutaneous injection of 1 mL 10% casein and rosiglitazone 4 mg/[kg d]. After 6 weeks, body weight, food intake, glucose and lipid parameters, and serum AST/ALT levels were measured after an overnight fast. Real time RT-PCR and immunohistochemical staining for various ER stress markers were performed, and a TUNEL analysis was also performed. After 6 weeks, casein injection induced weight reduction, systemic inflammation, and hepatic dysfunction in SD rats. Casein injection increased both the gene and protein expression of ER stress markers in the liver and also caused hepatocyte apoptosis. Rosiglitazone treatment attenuated casein-induced systemic inflammation, ER stress, deteriorated liver function, and increased apoptosis. In conclusion, our results may provide further insight into the effects of casein on chronic inflammatory diseases, and to have a better understanding of the mechanism of the anti-inflammatory properties of rosiglitazone regardless of its hypoglycemic effect.

High-sodium intake aggravates myocardial injuries induced by aldosterone via oxidative stress in Sprague-Dawley rats

To evaluate the effects of aldosterone with or without high sodium intake on blood pressure, myocardial structure and left ventricular function in rats, and to investigate the mechanisms underlying the effects. Eight-week-old male Sprague-Dawley rats were randomly divided into 3 groups: (1) control (CON) group fed a normal sodium diet, (2) aldosterone (ALD) group receiving aldosterone infusion and a normal sodium diet, and (3) high sodium plus aldosterone (HS-ALD) group receiving 1% NaCl diet in conjunction with aldosterone infusion. Aldosterone was administered through continuously subcutaneous infusion with osmotic minipump at the rate of 0.75 μg/h for 8 weeks. The myocardium structure was observed using transthoracic echocardiography and transmission electron microscopy. The collagen deposition in left ventricle was evaluated with Masson's trichrome staining. The expression of IL-18, p22phox, and p47phox proteins was examined using Western blot analysis. The systolic blood pressure in the ALD and HS-ALD groups was significantly higher than that in the CON group after 2-week treatment. But the blood pressure showed no significant difference between the HS-ALD and ALD groups. The left ventricular hypertrophy, myocardial collagen deposition and oxidative stress were predominantly found in the HS-ALD and ALD group. Furthermore, the breakdown of myocardial structure and oxidative stress were more apparent in the HS-ALD group as compared with those in the ALD group. Long-term infusion of aldosterone results in hypertension and profibrotic cardiovascular responses in rats fed a normal sodium diet, which were mediated by oxidative stress. High-sodium intake could aggravate myocardial injuries induced by aldosterone.

Ileal inducible nitric oxide synthase mRNA expression in response to stress is modified in Sprague-Dawley rats exposed to a previous intestinal inflammation

The ability of stress to initiate or reactivate an inflammatory process seems to depend on an individual's susceptibility to stressful stimuli. The aim of this study was to establish whether previous inflammation alters the response to stress in Sprague-Dawley rats, a strain not especially susceptible to stressful stimuli. Stress exposure was performed in rats treated with indomethacin, to induce cyclic intestinal inflammation, during the inactive phase of inflammation. Both control and indomethacin-treated rats submitted to stress showed a decrease in body weight gain and blood leukocyte levels, as well as an increase in fecal pellet output. The increase in intestinal mucosal mast cell count induced by stress was similar in both groups of animals. Moreover, no differences were observed between control and indomethacin-treated rats in the degree of bacterial translocation and myeloperoxidase levels after stress exposure. Despite these similarities, differences between groups were observed in inducible nitric oxide synthase (iNOS) mRNA expression. Although ileal iNOS mRNA expression was inhibited in healthy rats submitted to stress, stress failed to modify this parameter in indomethacin-treated rats. As iNOS is another inflammatory marker, our results may allow the possibility that a previous intestinal inflammation could change the intestinal susceptibility to stress. Whether these differences in ileal iNOS expression can be indicative of a possible change in the predisposition to develop an intestinal inflammatory reaction in response to stress in Sprague-Dawley rats remains to be elucidated.

Konjac glucomannan ameliorated high fat‐induced oxidative stress in rats

The aim of study was to determine ameliorative effects of konjac glucomannan (KGM), a viscous dietary fiber, on oxidative stress in Sprague‐Dawley rats fed a high‐fat fiber‐free diet. Six‐week‐old rats (n=8/group) were fed a normal‐fat (5% corn oil, w/w) fiber‐free, or high‐fat (25%, w/w) diets containing no fiber, KGM (5%, w/w) or inulin (5%, w/w, as a prebiotic control) for 4 weeks. The DNA damage of lymphocytes was determined by comet assay. In addition, lymphocytes were treated with formamidopyrimidine DNA‐glycosylase (FPG, 1 μg/mL) to determine its ability to defend oxidative stress. Plasma antioxidants and the malondialdehyde (MDA) levels in the plasma, liver and colon were also determined. Results indicated that the high‐fat fiber‐free diet significantly elevated lymphocyte DNA damage and MDA levels in the liver and colon, with a decrease in the plasma α‐tocopherol levels, as compared with its low‐fat counterpart. Incorporation of either KGM or inulin into the high‐fat fiber‐free diet significantly reduced the lymphocytes DNA damage and FPG‐induced lesion, and liver MDA levels. Furthermore, KGM and inulin significantly reduced the MDA level in the distal and proximal colon, respectively. Therefore, the present study suggests that KGM reduced oxidative stress caused by high‐fat diet in rats. This study was supported by the National Science Council Grant NSC‐99‐2320‐B‐040‐014‐MY2, Taipei, Taiwan.

Lentiviral-Human Heme Oxygenase Targeting Endothelium Improved Vascular Function in Angiotensin II Animal Model of Hypertension

We examined the hypothesis that vascular and renal dysfunction caused by angiotensin II (Ang II) through increased levels of blood pressure, inflammatory cytokines, and oxidative stress in Sprague-Dawley rats can be prevented by lentiviral-mediated delivery of endothelial heme oxygenase (HO)-1. We targeted the vascular endothelium using a lentiviral construct expressing human HO-1 under the control of the endothelium-specific promoter VE-cadherin (VECAD-HO-1) and examined the effect of long-term human HO-1 expression on blood pressure in Ang II-mediated increases in blood pressure and oxidant stress. A bolus injection of VECAD-HO-1 into the renal artery resulted in expression of human HO-1 for up to 6-9 weeks. Sprague-Dawley rats were implanted with Ang II minipumps and treated with lentivirus carrying either the HO-1 or green fluorescent protein. Renal tissue from VECAD-HO-1-transduced rats expresses human HO-1 mRNA and proteins without an effect on endogenous HO-1. Infusion of Ang II increased blood pressure (p < 0.001) but decreased vascular relaxation in response to acetylcholine, endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS) levels, and renal and plasma levels of adiponectin (p < 0.05); in contrast, plasma tumor necrosis factor-α and monocyte chemoattractant protein-1 levels increased. Ang II-treated animals had higher levels of superoxide anion and inducible nitric oxide synthase and increased urinary protein and plasma creatinine levels. Lentiviral transduction with the VECAD-HO-1 construct attenuated the increase in blood pressure (p < 0.05), improved vascular relaxation, increased plasma adiponectin, and prevented the elevation in urinary protein and plasma creatinine in Ang II-treated rats. Endothelial-specific expression of HO-1 also reduced oxidative stress and levels of inflammatory cytokines resulting in increased expression of the anti-apoptotic proteins phosphorylated AKT, phosphorylated AMP-activated protein kinase, peNOS, and eNOS. Collectively, these findings demonstrate that endothelial-specific increases in HO-1 expression attenuate Ang II hypertension and the associated vascular dysfunction that is associated with increases in adiponectin and peNOS and reductions in oxidative stress and levels of inflammatory cytokines.

Protective effect of hesperidin against γ-radiation induced oxidative stress in Sprague-Dawley rats

The high risk of human exposure to ionizing radiations during radiation therapy and also during space travel underscores the need to develop novel radioprotectors with improved efficacy. Increased oxidative stress and antioxidant deficit have been suggested to play a major role in radiation induced toxicity, and hence maintaining an antioxidant balance through dietary supplementation might provide beneficial effects during radiation exposure. The present study was designed to evaluate the effect of hesperidin, a flavanone glycoside found in citrus plants, on the antioxidant defense system and lipid peroxidation against γ-radiation induced damage in rats. Exposure of rats to γ-radiation (5 Gy) resulted in tissue damage characterized by significantly elevated levels of serum marker enzymes (AST, ALT, ALP, LDH, and CPK) and a decrease in their activities in the heart tissue. γ-Radiation induced oxidative stress was observed by elevated levels of lipid peroxidation and a decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, and GSH) in the heart and kidney of rats. Post-treatment with hesperidin (50 and 100 mg/kg bw/day, orally) for 7 days following exposure to γ-radiation significantly attenuated these changes when compared to the radiation exposed groups. Histopathological examination of the heart tissue of rats exposed to γ-radiation and treated with hesperidin also showed minimal damage when compared to those exposed to γ-radiation alone. These findings indicate the protective effect of hesperidin on lipid peroxidation and the antioxidant tissue defense system during γ-radiation induced tissue damage in rats.

Protective effect of palm vitamin E and α-tocopherol against gastric lesions induced by water immersion restraint stress in Sprague-Dawley rats.

Objective:Stress can lead to various changes in the gastrointestinal tract of rats. The present study was designed to compare the effect of palm vitamin E (PVE) and α-tocopherol (α-TF) supplementations on the gastric parameters important in maintaining gastric mucosal integrity in rats exposed to water immersion restraint stress (WRS). These parameters include gastric acidity, plasma gastrin level, gastric prostaglandin E2 (PGE2), and gastric lesions.Materials and Methods:Sixty male Sprague-Dawley rats (200-250 g) were divided into three equal groups: a control group, which received a normal rat diet (RC), and two treatment groups, receiving oral supplementation of either PVE or α-TF at 60 mg/kg body weight for 28 days. Each group was further divided into two groups: the nonstress and stress groups. The stress groups were subjected to 3.5 h of WRS once at the end of the treatment period. Blood samples were then taken to measure the gastrin level, after which the rats were killed. Gastric juice was collected for measurement of gastric acidity and gastric tissue was taken for measurement of gastric mucosal lesions and PGE2.Results:Exposure to stress resulted in the production of gastric lesions. PVE and α-TF lowered the lesion indices as compared to the stress control group. Stress reduced gastric acidity but pretreatment with PVE and α-TF prevented this reduction. The gastrin levels in the stress group were lower as compared to that in the nonstress control. However, following treatment with PVE and α-TF, gastrin levels increased and approached the normal level. There was also a significant reduction in the gastric PGE2 content with stress exposure, but this reduction was blocked with treatment with both PVE and α-TF.Conclusion:In conclusion, WRS leads to a reduction in the gastric acidity, gastrin level, and gastric PGE2 level and there is increased formation of gastric lesions. Supplementation with either PVE or α-TF reduces the formation of gastric lesions, possibly by blocking the changes in the gastric acidity, gastrin, and gastric PGE2 induced by stress. No significant difference between PVE and α-TF was observed.

Effect of voluntary wheel running on circadian corticosterone release and on HPA axis responsiveness to restraint stress in Sprague-Dawley rats

Adaptations of the hypothalamic-pituitary-adrenal (HPA) axis to voluntary exercise in rodents are not clear, because most investigations use forced-exercise protocols, which are associated with psychological stress. In the present study, we examined the effects of voluntary wheel running on the circadian corticosterone (Cort) rhythm as well as HPA axis responsiveness to, and recovery from, restraint stress. Male Sprague-Dawley rats were divided into exercise (E) and sedentary (S) groups, with E rats having 24-h access to running wheels for 5 wk. Circadian plasma Cort levels were measured at the end of each week, except for week 5 when rats were exposed to 20 min of restraint stress, followed by 95 min of recovery. Measurements of glucocorticoid receptor content in the hippocampus and anterior pituitary were performed using Western blotting at the termination of the restraint protocol. In week 1, circadian Cort levels were twofold higher in E compared with S animals, but the levels progressively decreased in the E group throughout the training protocol to reach similar values observed in S by week 4. During restraint stress and recovery, Cort values were similar between E and S, as was glucocorticoid receptor content in the hippocampus and pituitary gland after death. Compared with E, S animals had higher plasma ACTH levels during restraint. Taken together, these data indicate that 5 wk of wheel running are associated with normal circadian Cort activity and normal negative-feedback inhibition of the HPA axis, as well as with increased adrenal sensitivity to ACTH after restraint stress.

Effect Of Voluntary Training On Glucocorticoid Responsiveness To Restraint Stress In Sprague-Dawley Rats

Effect Of Voluntary Training On Glucocorticoid Responsiveness To Restraint Stress In Sprague-Dawley Rats