Oxidative Stress In Adult Rats Research Articles

Hydroalcoholic Extract of Centella asiatica and Madecassic Acid Reverse Depressive-Like Behaviors, Inflammation and Oxidative Stress in Adult Rats Submitted to Stress in Early Life.

Major depressive disorder (MDD) is a severe disorder that causes enormous loss of quality of life, and among the factors underlying MDD is stress in maternal deprivation (MD). In addition, classic pharmacotherapy has presented severe adverse effects. Centella asiatica (C. asiatica) demonstrates a potential neuroprotective effect but has not yet been evaluated in MD models. This study aimed to evaluate the effect of C. asiatica extract and the active compound madecassic acid on possible depressive-like behavior, inflammation, and oxidative stress in the hippocampus and serum of young rats submitted to MD in the first days of life. Rats (after the first day of birth) were separated from the mother for 3h a day for 10days. When adults, these animals were divided into groups and submitted to treatment for 14days. After subjecting the animals to protocols of locomotor activity in the open field and behavioral despair in the forced swimming test, researchers then euthanized the animals. The hippocampus and serum were collected and analyzed for the inflammatory cytokines and oxidative markers. The C. asiatica extract and active compound reversed or reduced depressive-like behaviors, inflammation in the hippocampus, and oxidative stress in serum and hippocampus. These results suggest that C. asiatica and madecassic acid have potential antidepressant action, at least partially, through anti-inflammatory and antioxidant profiles.

Melatonin Ameliorates Valproic Acid-Induced Neurogenesis Impairment: The Role of Oxidative Stress in Adult Rats.

Background Valproic acid (anticonvulsant medication) has been found to inhibit histone deacetylase activity and suppress hippocampal neurogenesis, which causes memory impairment in both humans and rodents. The neurohormone melatonin, which regulates mammalian seasonal and circadian physiology, has recently been shown to have neuroprotective properties, counteracting memory impairment associated with VPA-caused hippocampal neurogenesis reduction. This study is aimed at investigating the molecular mechanisms of melatonin associated with VPA-induced hippocampal neurogenesis and memory impairment. Methods Male Spraque-Dawley rats received VPA (300 mg/kg) twice daily or melatonin (8 mg/kg/day) or some rats were given melatonin for 14 days during VPA administration. Results The VPA-treated rats showed a significant increase in malondialdehyde (MDA) levels in the hippocampus and p21-positive cells in the subgranular zone (SGZ) of the dentate gyrus (DG) but decreased superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities. Moreover, VPA significantly decreased levels of nestin, Notchl, nuclear factor erythroid 2-related factor 2 (Nrf2), doublecortin (DCX), sex determining region Y-box 2 (SOX2), and brain-derived neurotrophic factor (BDNF). Conclusions We found that melatonin was able to counteract these neurotoxic effects, acting as a neuroprotectant in VPA-induced memory hippocampal neurogenesis impairment by preventing intracellular oxidative stress and increasing antioxidant activity.

Protective Effect of Hydroalcoholic Extract of Solanum surattense on Brain Tissue Damage and Oxidative Stress in Adult Rats with Toxoplasmosis

Introduction: Toxoplasmosis is caused by a protozoan named Toxoplasma gondii. This protozoan is a parasite of cats that can spread among other animals and birds around the world and cause a disease that varies from mild to severe. The disease is seen in the forms of acquired toxoplasmosis and congenital toxoplasmosis. Many studies have shown that there is a relationship between reproductive function and toxoplasmosis. T. gondii has led to decreased reproductive performance of males and females in many experimental animals. The aim of this study was to investigate the protective effect of hydroalcoholic extract of Solanum surattense on the brain tissue damage and brain oxidative stress induced by T. gondii in adult rats. Methods: For this purpose, 32 adult female rats were randomly divided into 4 groups. In group 1, 8 healthy rats received IP saline for 3 weeks. In group 2, 8 rats with T. gondii received IP saline for 3 weeks. In group 3, 8 rats with T. gondii received the hydroalcoholic extract of S. surattense for 3 weeks. In group 4, 8 healthy rats received the hydroalcoholic extract of S. surattense for 3 weeks. Then, brain tissue resection was performed to evaluate histological damage and levels of antioxidant enzymes. Results: Histological and biochemical studies showed that T. gondii had a deleterious effect on the brain tissue of rats and increased the level of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The administration of hydroalcoholic extract of S. surattense improved these effects due to its high antioxidant properties. Conclusion: The administration of the appropriate dose of hydroalcoholic extract of S. surattense for three consecutive weeks had a protective effect on brain tissue exposed to T. gondii.

Effect of adiantum capillus veneris against irradiation-induced oxidative stress in adult rats

Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues.

Prepubertal exposure to genistein alleviates di-(2-ethylhexyl) phthalate induced testicular oxidative stress in adult rats.

Di-(2-ethylhexyl) phthalate (DEHP) is the most widely used plastizer in the world and can suppress testosterone production via activation of oxidative stress. Genistein (GEN) is one of the isoflavones ingredients exhibiting weak estrogenic and potentially antioxidative effects. However, study on reproductive effects following prepubertal multiple endocrine disrupters exposure has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from postnatal day 22 (PND22) to PND35 with vehicle control, GEN at 50 mg/kg body weight (bw)/day (G), DEHP at 50, 150, 450 mg/kg bw/day (D50, D150, D450) and their mixture (G + D50, G + D150, G + D450). On PND90, general morphometry (body weight, AGD, organ weight, and organ coefficient), testicular redox state, and testicular histology were studied. Our results indicated that DEHP could significantly decrease sex organs weight, organ coefficient, and testicular antioxidative ability, which largely depended on the dose of DEHP. However, coadministration of GEN could partially alleviate DEHP-induced reproductive injuries via enhancement of testicular antioxidative enzymes activities, which indicates that GEN has protective effects on DEHP-induced male reproductive system damage after prepubertal exposure and GEN may have promising future in its curative antioxidative role for reproductive disorders caused by other environmental endocrine disruptors.

Antioxidant capacity responsible for a hypocholesterolemia is independent of dietary cholesterol in adult rats fed rice protein

Dietary cholesterol and aging are major risk factors to accelerate oxidation process for developing hypercholesterolemia. The major aim of this study is to elucidate the effects of rice protein on cholesterol level and oxidative stress in adult rats fed with and without cholesterol. After 2weeks of feeding, hepatic and plasma contents of cholesterol, reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA) and protein carbonyl (PCO) were measured. In liver, total antioxidative capacity (T-AOC), activities of antioxidant enzymes (total superoxide dismutase, T-SOD; catalase, CAT), glutathione metabolizing enzyme activities and gene expression levels (γ-glutamylcysteine synthetase, γ-GCS; glutathione reductase, GR; glutathione peroxidase, GPx) were determined. Under cholesterol-free/enriched dietary condition, T-AOC, activities of T-SOD and CAT, glutathione metabolism related enzymes' activities and mRNA levels (γ-GCS, GR and GPx) were effectively stimulated by rice proteins as compared to caseins. Compared with caseins, rice proteins significantly increased hepatic and plasma GSH contents, whereas hepatic and plasma accumulations of MDA, PCO and GSSG were significantly reduced by rice protein-feedings. As a result, the marked reductions of cholesterol in the plasma and in the liver were observed in adult rats fed rice proteins with and without cholesterol. The present study demonstrates that the hypocholesterolemic effect of rice protein is attributable to inducing antioxidative response and depressing oxidative damage in adult rats fed cholesterol-free/enriched diets. Results suggest that the antioxidant capability involved in the hypocholesterolemic action exerted by rice protein is independent of dietary cholesterol during adult period.

Developmental Programming of eNOS Uncoupling and Enhanced Vascular Oxidative Stress in Adult Rats After Transient Neonatal Oxygen Exposure

The authors have previously shown that neonatal hyperoxic stress leads to high blood pressure, impaired endothelium-mediated vasodilatation, and increased vascular production of superoxide anion by NAD(P)H oxidase in adulthood. However, it is unknown whether changes in nitric oxide (NO) production and/or bioinactivation prevail and whether NO synthase (NOS) is also a source of superoxide. The purpose of this study was to evaluate whether adult animals exposed to neonatal hyperoxic stress have impaired vascular NO production associated with NOS uncoupling participating to vascular superoxide production and vascular dysfunction. In adult male rats exposed to 80% oxygen from day 3 to 10 of life (H, n = 6) versus room air controls (CTRL, n = 6), vascular (aorta) NO production is decreased at baseline (CTRL: 21 ± 1 vs. H: 16 ± 2 4,5-diaminofluorescein diacetate fluorescence intensity arbitrary units; P < 0.05) and after carbachol stimulation (acetylcholine analog; CTRL: 26 ± 2 vs. H: 18±2; P < 0.05). Pretreatment with L-arginine (CTRL: 32 ± 4 vs. H: 31 ± 5) and L-sepiapterine [analog of key NOS cofactor tetrahydro-L-biopterin (BH4)] (CTRL: 30 ± 3 vs. H: 29 ± 3) normalizes NO production after carbachol. L-Sepiapterine also normalizes impaired vasodilatation to carbachol. Vascular endothelial NO synthase (eNOS) immunostaining is reduced, whereas total eNOS protein expression is increased in H (CTRL: 0.76 ± 0.08 vs. H: 1.76± 0.21; P < 0.01). The significantly higher superoxide generation (CTRL: 20 ± 2 vs. H: 28 ± 3 hydroethidine fluorescence intensity arbitrary units; P < 0.05) is prevented by pretreatment with the eNOS inhibitor N-nitro-L-arginine methyl ester (CTRL: 21 ± 4 vs. H: 22 ± 4). Taken together, the current data indicate a role for eNOS uncoupling in enhanced vascular superoxide, impaired endothelium-mediated vasodilatation, and decreased NO production in adult animals with programmed elevated blood pressure after a brief neonatal oxygen exposure.

Protective effects of vitamin C and selenium supplementation on methomyl-induced tissue oxidative stress in adult rats

Methomyl (MET) is used worldwide in agriculture and health programs. Besides its advantages in the agriculture, it causes several toxic effects. The objective of this study was to examine the potential ability of vitamin C and/or selenium (Se), to alleviate the oxidative damage parameters, against MET-induced changes in blood biochemical markers and oxidative damage in liver and kidney of male Wistar rats. The animals were randomized into five groups of eight each: group I served as control rats; group II received MET (8mg/kgbody weight (BW)) in drinking water; group III received both MET and vitamin C (200mg/kg BW; by intraperitoneal injection); group IV received both MET and Se (0.6mg/100gBW). Animals of group V were treated with MET, vitamin C and Se. A significant increase in the levels of hepatic markers enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase) was determined. Furthermore, renal markers such as urea and creatinine were increased in MET-treated rats. Additionally, serum cholesterol and triglycerides were significantly enhanced. Exposure of rats to MET caused significant increase in malondialdehyde levels, thus causing a drastic alteration in antioxidant defense system, particularly in the activities of catalase and glutathione-S-transferase and glutathione peroxidase. However, simultaneous supplementation with vitamin C and Se restored these parameters partially. In conclusion, the results of the current study revealed that MET-induced toxicity caused perturbations of some biochemical parameters, lipid peroxidation and alterations in the antioxidant enzymes in liver and kidney homogenates. Administration of vitamin C and Se exhibited protective effect by inhibiting MET-induced toxicity in liver and kidney.

Effect of selenium on methimazole-induced liver damage and oxidative stress in adult rats and their offspring

This study aimed to investigate the protective effect of selenium (Se) on methimazole (MMI; an antithyroid drug)-induced hepatotoxicity in adult rats and their progeny. Female Wistar rats were randomly divided into four groups of six rats in each group: group I served as controls that received standard diet; group II received MMI in drinking water as 250mgL(-1) and standard diet; group III received both MMI (250mgL(-1), orally) and Se (0.5mgkg(-1) of diet); group IV received Se (0.5mgkg(-1) of diet) as sodium selenite. Treatments were started from the 14th day of pregnancy until day 14 after delivery. Exposure of rats to MMI promoted oxidative stress with an increase in liver malondialdehyde levels, advanced oxidation protein products and protein carbonyl contents and a decrease in the levels of glutathione, nonprotein thiols and vitamin C. A decrease in the activities of liver glutathione peroxidase, superoxide dismutase, catalase and lactate dehydrogenase and in the levels of plasma total protein and albumin was also observed. Plasma transaminase activities and total, direct and indirect bilirubin levels increased. Coadministration of Se through diet improved all biochemical parameters. The histopathological changes confirmed the biochemical results. Therefore, our investigation revealed that Se, a trace element with antioxidant properties, was effective in preventing MMI-induced liver damage.

The effects of immunosuppressants on vascular function, systemic oxidative stress and inflammation in rats

Immunosuppressants have been associated with increased cardiovascular disease risk. We determined the effects of calcineurin and mammalian target of rapamycin (mTOR) inhibitor administration on endothelial dysfunction and associated inflammation and oxidative stress in adult rats. Cyclosporine A (low and high dose), sirolimus, tacrolimus, everolimus and placebo were administered to 8-week-old male Wistar rats for 10 consecutive days. Aortic vascular endothelial and smooth muscle function were assessed ex vivo in organ baths. Maximal aortic contraction to noradrenaline in sirolimus-treated rats was significantly greater than cyclosporine groups, everolimus and placebo, whereas endothelial-dependent relaxation was significantly impaired with cyclosporine and tacrolimus compared with everolimus. Endothelial-independent relaxation was impaired in tacrolimus-treated rats compared with low dose cyclosporine, everolimus and sirolimus. Sirolimus was associated with a reduction in plasma interleukin (IL)-1β and tumour necrosis factor (TNF)-α and higher levels of catalase and total antioxidant status. In nontransplanted rats, vascular dysfunction was evident following administration of cyclosporine A, sirolimus and tacrolimus, whereas everolimus did not compromise aortic endothelial or smooth muscle function. At the doses administered in this model, the immunosuppressants exerted varying effects on vascular function.

Municipal landfill leachate induces hepatotoxicity and oxidative stress in rats

Human beings are more often exposed to complex mixtures of hazardous chemicals than single toxicant. The present study investigated the effects of Olushosun municipal landfill leachate (OMLL) from Ojota in Lagos State of Nigeria on hepatic function and some biomarkers of oxidative stress in adult rats. Physicochemical characteristic analysis of OMLL showed that while total alkalinity, total acidity, total hardness, biochemical oxygen demand and chemical oxygen demand were 3-fold, 2-fold, 4-fold and 1-fold, respectively, concentrations of heavy metals analysis showed that copper, lead, cadmium, arsenic, cobalt, chromium and mercury were 9-fold, 4-fold, 21-fold, 1320-fold, 7-fold, 5-fold and 4-fold, respectively, higher than acceptable limits by regulatory authorities. The OMLL was administered at 0, 10, 20, 30 and 40% concentrations to adult male rats for 14 days. Following exposure, serum was collected for serum biochemistry assays and liver was collected to determine the antioxidant status. Exposure of animals to 10, 20, 30 and 40% OMLL resulted in 3%, 31%, 52% and 83% increase in aspartate aminotransferase activity, whereas it elevated alanine aminotransferase activity by 10%, 25%, 30% and 49%, respectively, when compared with the control. While OMLL administration significantly increased catalase activity, a sequential decrease in reduced glutathione level and in superoxide dismutase and glutathione-S-transferase activities with concomitant increase in malondialdehyde level were observed, when compared with the control. Collectively, the hepatotoxicity of OMLL could be due to the induction of oxidative stress and may suggest possible health hazards in subjects with occupational or environmental exposure.

Protective effects of selenium on methimazole-induced anemia and oxidative stress in adult rats and their offspring

The present study investigates the potential ability of selenium, considered as an antioxidant with pharmacological property to alleviate oxidative stress and hematological parameter disorders induced by methimazole, an antithyroid drug. Pregnant Wistar rats were randomly divided into four groups of six each: group I served as negative control and received a standard diet; group II received 250 mg/L of methimazole in drinking water and a standard diet; group III received both methimazole (250 mg/L, orally) and selenium (0.5 mg/kg of diet) supplemented to the standard diet; group IV served as positive control and received a supplement of selenium in the diet (0.5 mg/kg of diet) as sodium selenite (Na(2)SeO(3)). Treatment was started from the 14th day of pregnancy until day 14 after delivery. Methimazole reduced the number of red blood cells, hemoglobin concentration and hematocrit in mothers and their pups. Besides, plasma iron, vitamins B(9), B(12), C and E levels were reduced. Lipid peroxidation increased, objectified by high malondialdehyde levels and lactate dehydrogenase activity in plasma, while glutathione, glutathione peroxidase, superoxide dismutase and catalase activities showed a significant decline. Co-administration of selenium through diet improved all the parameters cited above. It can be concluded that the administration of selenium alleviates methimazole-induced toxicity, thus demonstrating its antioxidant efficacy.

Brain in the Brawn

Nitric oxide (NO) plays a central role in the regulation of cardiovascular homeostasis and is involved in the regulation of vascular tone and cardiac contractility as well as gene expression and cell proliferation. Furthermore, NO modulates renin secretion and salt and fluid reabsorption in the kidney.1 Three isoforms of NO synthase (NOS) have been identified, the neuronal NOS (nNOS or NOS I), the inducible NOS (iNOS or NOS II), and the endothelial NOS (eNOS or NOS III). While all of these enzymes potentially affect blood pressure, only eNOS-deficient mice are hypertensive.2,3 Although nNOS is expressed in cardiac myocytes,4,5 as well as in vascular smooth muscle cells,6–8 relatively little is known about the role played by nNOS-derived NO in cardiovascular homeostasis. Both pro- and antihypertensive actions have been attributed to nNOS, and selective inhibitors of this isoform have been reported to normalize blood pressure,9 as well as to attenuate flow-induced vasodilatation in eNOS−/− mice.8 The regulation of nNOS activity, like that of eNOS, is determined by phosphorylation of the enzyme as well as by its association with a number of regulatory proteins.10 One protein that associates with nNOS in human embryonic kidney (HEK293) cells and is reported to play a major role in regulating the activity of the Ca2+-dependent enzyme, is the plasma membrane Ca2+/calmodulin-dependent Ca2+-ATPase (PMCA).11 The ATPase binds to nNOS via an interaction between its carboxyl terminus and the PDZ domain of nNOS. Increasing expression of the PMCA4b isoform markedly attenuates NO synthesis by nNOS, an effect not observed in cells overexpressing a mutant PMCA that was devoid of Ca2+-transporting activity.11 Thus, …

Plasma protein carbonyl concentration is not enhanced by chronic intake of high-protein diets in adult rats

We tested the hypothesis of whether high dietary protein intake is linked to oxidative stress as measured by the concentration of reactive carbonyl residues in plasma proteins. Three groups of male Wistar rats (∼230 g, n = 10) were fed either 15% (15C), 30% (30C), or 60% (60C) casein diets over a period of 18 weeks. For comparison, a vitamin E deficient diet (60C-E) based on diet 60C was given to an additional group to provoke oxidative stress. Concentrations of α-tocopherol in plasma and of reactive carbonyl residues in total plasma proteins were measured by high performance liquid chromatography using fluorescence and by diode array detection after 2,4-dinitrophenylhydrazine reaction, respectively. After 1 week the concentration of reactive carbonyl residues in plasma proteins was found to be significantly ( P < 0.05) higher in the 60C and 60C-E groups (∼2.7 nmol/mg protein) compared with the 15C and 30C groups (∼1.7 nmol/mg protein). After 14 weeks the 15C (3.4 ± 1.2 nmol/mg protein) and 60C-E groups (3.9 ± 1.7 nmol/mg protein) showed a significantly increased concentration of reactive carbonyl residues in plasma protein compared with the 30C and 60C groups (2.5 ± 1.0 nmol/mg protein; 2.6 ± 0.8 nmol/mg protein). As expected, chronic vitamin E deficiency (60C-E) resulted in significantly decreased α-tocopherol concentrations (3.91 ± 2.42 μmol/mL vs. 31.3 ± 4.8 μmol/mL) and a higher concentration of reactive carbonyl residues in plasma proteins. These results do not support the hypothesis that a chronic intake of high-protein diets leads to oxidative stress in adult rats. However, in the non-adapted state (1 week) a high protein intake contributes to oxidative modifications of protein-bound amino acid residues.