Oxidative 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.

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>

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.

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.

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.

Effects of Dietary Supplements on Space Radiation-Induced Oxidative Stress in Sprague-Dawley Rats

Of particular concern for the health of astronauts during space travel is radiation from protons and high-mass, high-atomic-number (Z), and high-energy particles (HZE particles). Space radiation is known to induce oxidative stress in astronauts after extended space flight. In the present study, the total antioxidant status was used as a biomarker to evaluate oxidative stress induced by gamma rays, protons and HZE-particle radiation. The results demonstrate that the plasma level of total antioxidants in Sprague-Dawley rats was significantly decreased (P < 0.01) in a dose-dependent manner within 4 h after exposure to gamma rays. Exposure to protons and HZE-particle radiation also significantly decreased the serum or plasma level of total antioxidants in the irradiated animals. Diet supplementation with L-selenomethionine alone or a combination of selected antioxidant agents was shown to partially or completely prevent the decrease in the serum or plasma levels of total antioxidants in animals exposed to gamma rays, protons or HZE particles. These findings suggest that exposure to space radiation may compromise the capacity of the host antioxidant defense and that this adverse biological effect can be prevented at least partially by dietary supplementation with L-selenomethionine and antioxidants.