Different susceptibility of prefrontal cortex and hippocampus to oxidative stress following chronic social isolation stress

Chronic oxidative stress plays an important role in depression. The aim of present study was to examine the stress-induced changes in serum corticosterone (CORT) levels, cytosolic protein carbonyl groups, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO) and total superoxide dismutase (SOD) activity in the prefrontal cortex versus hippocampus of male Wistar rats exposed to acute (2 h of immobilization or cold), chronic (21d of social isolation) stress, and their combination (chronic + acute stress). The subcellular distribution of nuclear factor-κB (NF-κB) and cytosolic cyclooxygenase 2 (COX-2) protein expressions were also examined. Depressive- and anxiety-like behaviors were assessed via the forced swim, sucrose preference, and marble burying tests in chronically isolated rats. Although both acute stressors resulted in elevated CORT, increased MDA in the prefrontal cortex and NF-κB activation accompanied by increased NO in the hippocampus were detected only following acute cold stress. Chronic isolation resulted in no change in CORT levels, but disabled appropriate response to novel acute stress and led to depressive- and anxiety-like behaviors. Increased oxidative/nitrosative stress markers, likely by NF-κB nuclear translocation and concomitant COX-2 upregulation, associated with decreased SOD activity and GSH levels, suggested the existence of oxidative stress in the prefrontal cortex. In contrast, hippocampus was less susceptible to oxidative damage showing only increase in protein carbonyl groups and depleted GSH. Taken together, the prefrontal cortex seems to be more sensitive to oxidative stress than the hippocampus following chronic isolation stress, which may be relevant for further research related to stress-induced depressive-like behavior.     

Serum Myeloperoxidase Activity, Total Antioxidant Capacity and Nitric Oxide Levels in Patients with Chronic Otitis Media

It has been suggested that oxidative stress may play an important role in the pathogenesis of chronic otitis media (COM), but the role of oxidative stress in the pathogenesis of COM has not yet been fully explored. Therefore, the aim of this study was to investigate serum myeloperoxidase (MPO) activity, 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), total antioxidant capacity (TAC) and nitric oxide (NO) in patients with COM. Sixty-one patients with COM and 30 controls were enrolled in the present study. Patients were divided into two groups according to the presence (n = 21) or absence (n = 40) of cholesteatoma. Serum MPO activity and 4-HNE, MDA and NO levels were significantly higher in patients with COM than controls (for all, p < 0.001), while TAC levels were significantly lower (for all, p < 0.001). Serum MPO activity and MDA, 4-HNE and NO levels were significantly higher in patients with cholesteatoma than in those without cholesteatoma, while TAC levels were significantly lower; but the difference between groups was not statistically significant (p > 0.05). Increased oxidative stress seems to be associated with decreased antioxidant levels in patients with COM. Thus, increased oxidative stress may play a role in the pathogenesis of COM. It is believed that the administration of antioxidant vitamins such as A, C and E may be useful in preventing and treating COM.     

Flacourtia indica fruit extract modulated antioxidant gene expression,prevented oxidative stress and ameliorated kidney dysfunction in isoprenaline administered rats

This study evaluated the effect of Flacourtia indica fruit extract against isoprenaline (ISO) induced renal damage in rats. This investigation showed that ISO administration in rats increased the level oxidative stress biomarkers such as malondialdehyde (MDA), nitric oxide (NO), advanced protein oxidation product (APOP) in kidneys followed by a decrease in antioxidant enzymes functions. Flacourtia indica fruit extract, which is rich in strong antioxidants, also reduced the MDA, NO and APOP level in kidney of ISO administered rats. Inflammation and necrosis was also visible in kidney section of ISO administered rats which was significantly prevented by atenolol and Flacourtia indica fruit extract. Moreover, atenolol and Flacourtia indica fruit extract also modulated the genes expressions related to inflammation and oxidative stress in kidneys. The beneficial effects could be attributed to the presence of a number of phenolic antioxidants. This study suggests that Flacourtia indica fruit extract may prevent kidney dysfunction in ISO administered rats, probably by preventing oxidative stress and inflammation.     

l-Tyrosine Induces DNA Damage in Brain and Blood of Rats

Mutations in the tyrosine aminotransferase gene have been identified to cause tyrosinemia type II which is inherited in an autosomal recessive manner. Studies have demonstrated that an excessive production of ROS can lead to reactions with macromolecules, such as DNA, lipids, and proteins. Considering that the l-tyrosine may promote oxidative stress, the main objective of this study was to investigate the in vivo effects of l-tyrosine on DNA damage determined by the alkaline comet assay, in brain and blood of rats. In our acute protocol, Wistar rats (30 days old) were killed 1 h after a single intraperitoneal l-tyrosine injection (500 mg/kg) or saline. For chronic administration, the animals received two subcutaneous injections of l-tyrosine (500 mg/kg, 12-h intervals) or saline administered for 24 days starting at postnatal day (PD) 7 (last injection at PD 31), 12 h after the last injection, the animals were killed by decapitation. We observed that acute administration of l-tyrosine increased DNA damage frequency and damage index in cerebral cortex and blood when compared to control group. Moreover, we observed that chronic administration of l-tyrosine increased DNA damage frequency and damage index in hippocampus, striatum, cerebral cortex and blood when compared to control group. In conclusion, the present work demonstrated that DNA damage can be encountered in brain from animal models of hypertyrosinemia, DNA alterations may represent a further means to explain neurological dysfunction in this inherited metabolic disorder and to reinforce the role of oxidative stress in the pathophysiology of tyrosinemia type II.     

Chronic mitochondrial uncoupling treatment prevents acute cold-induced oxidative stress in birds

Endotherms have evolved two major types of thermogenesis that allow them to actively produce heat in response to cold exposure, either through muscular activity (i.e. shivering thermogenesis) or through futile electro-chemical cycles (i.e. non-shivering thermogenesis). Amongst the latter, mitochondrial uncoupling is of key importance because it is suggested to drive heat production at a low cost in terms of oxidative stress. While this has been experimentally shown in mammals, the oxidative stress consequences of cold exposure and mitochondrial uncoupling are clearly less understood in the other class of endotherms, the birds. We compared metabolic and oxidative stress responses of zebra finches chronically treated with or without a chemical mitochondrial uncoupler (2,4-dinitrophenol: DNP), undergoing an acute (24 h) and a chronic (4 weeks) cold exposure (12 °C). We predicted that control birds should present at least a transient elevation of oxidative stress levels in response to cold exposure. This oxidative stress cost should be more pronounced in control birds than in DNP-treated birds, due to their lower basal uncoupling state. Despite similar increase in metabolism, control birds presented elevated levels of DNA oxidative damage in response to acute (but not chronic) cold exposure, while DNP-treated birds did not. Plasma antioxidant capacity decreased overall in response to chronic cold exposure. These results show that acute cold exposure increases oxidative stress in birds. However, uncoupling mitochondrial functioning appears as a putative compensatory mechanism preventing cold-induced oxidative stress. This result confirms previous observations in mice and underlines non-shivering thermogenesis as a putative key mechanism for endotherms in mounting a response to cold at a low oxidative cost.     

Content of Minerals and Fatty Acids and Their Correlation with Phytochemical Compounds and Antioxidant Activity of Leguminous Seeds

This study was carried out to determine the effect of zinc on oxidative DNA damage in rats with experimental acute and chronic kidney deficiency. Six groups of five Wistar-Albino rats each were assigned as controls (C), acute kidney deficiency (AKD), zinc-supplemented (+Zn), acute kidney deficiency, zinc-supplemented (AKD + Zn), chronic kidney deficiency (CKD) and zinc-supplemented chronic kidney deficiency (CKD + Zn). The levels of 8-Oxo-2′-deoxyguanosine (8-OHdG) were determined, being the lowest in the CKD group (p < 0.05), higher in the C group than those of rats with CKD but lower than that of all the other groups (p < 0.05). There were no significant differences between the controls and the CKD + Zn group, or between the AKD and the +Zn groups. Among all groups, the highest 8-OHdG level was found in the AKD + Zn group (p < 0.05). DNA damage was greater in acute renal failure than in rats with chronic renal failure. The DNA damage in the zinc group was significantly higher than in the controls.     

Effects of Lithium and Lamotrigine on Oxidative–Nitrosative Stress and Spatial Learning Deficit After Global Cerebral Ischemia

Lithium (Li) and lamotrigine (LTG) have neuroprotective properties. However, the exact therapeutic mechanisms of these drugs have not been well understood. We investigated the antioxidant properties of Li (40 and 80 mg/kg/day) and LTG (20 and 40 mg/kg/day) in a rat model of global cerebral ischemia based on permanent bilateral occlusion of the common carotid arteries (BCAO). Nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GSH-R), catalase (CAT) and superoxide dismutase (SOD) levels were measured as an indicator of oxidative–nitrosative stress in both prefrontal cortex (PFC) and hippocampus after 28 days of treatment. The spatial learning disability was also assessed at the end of the study by Morris water maze (MWM) test. All oxidative–nitrosative parameters were found to be higher in the groups under treatment than in sham. Both drugs caused a decrease in PFC NO and MDA elevation, meanwhile the increase in GSH, GSH-R, CAT and SOD levels was significantly more evident in treated groups. We also found higher PFC GSH-R and hippocampal SOD levels in BCAO + Li (80 mg/day) treated group when compared with BCAO + LTG 40 mg/day. MWM test data showed a similar increase in spatial learning ability in all groups under treatment. We found no other statistical difference in comparison of treated groups with different dosages. Our findings suggested that Li and LTG treatments may decrease spatial learning memory deficits accompanied by lower oxidative–nitrosative stress in global cerebral ischemia. Both drugs may have potential benefits for the treatment of vascular dementia in clinical practice.     

Effect of 900-, 1800-, and 2100-MHz radiofrequency radiation on DNA and oxidative stress in brain

Ubiquitous and ever increasing use of mobile phones led to the growing concern about the effects of radiofrequency radiation (RFR) emitted by cell phones on biological systems. The aim of this study is to explore whether long-term RFR exposure at different frequencies affects DNA damage and oxidant-antioxidant parameters in the blood and brain tissue of rats. 28 male Sprague Dawley rats were randomly divided into four equal groups (n = 7). They were identified as Group 1: sham-control, Group 2: 900 MHz, Group 3: 1800 MHz, and Group 4: 2100 MHz. Experimental groups of rats were exposed to RFR 2 h/day for 6 months. The sham-control group of rats was subjected to the same experimental condition but generator was turned off. Specific absorption rates (SARs) at brain with 1 g average were calculated as 0.0845 W/kg, 0.04563 W/kg, and 0.03957, at 900 MHz, 1800 MHz, and 2100 MHz, respectively. Additionally, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), total antioxidant status (TAS), and total oxidant status (TOS) analyses were conducted in the brain tissue samples. Results of the study showed that DNA damage and oxidative stress indicators were found higher in the RFR exposure groups than in the sham-control group. In conclusion, 900-, 1800-, and 2100-MHz RFR emitted from mobile phones may cause oxidative damage, induce increase in lipid peroxidation, and increase oxidative DNA damage formation in the frontal lobe of the rat brain tissues. Furthermore, 2100-MHz RFR may cause formation of DNA single-strand breaks.     

The effects of zofenopril on cardiac function and pro-oxidative parameters in the streptozotocin-induced diabetic rat heart

Diabetes mellitus is a chronic condition that continues to increase in both incidence and prevalence. Renin–Angiotensin–Aldosterone System is one of the main modulators of chronic hyperglycaemia and, thus, its influence on tissues. Hyperglycaemia-induced oxidative stress is an important factor in diabetic cardiomyopathy. The present study was carried out on 24 adult male Wistar albino rats (8-week-old and with body masses of 190 ± 10 g). We evaluated the influence of acute administration of zofenopril on ex vivo myocardial function from rats with streptozotocin-induced diabetes mellitus, with a special emphasis on cardiodynamic and oxidative stress parameters in diabetic rat hearts. Rats were divided randomly into two groups (12 animals per group): control non-diabetic animals (C) were healthy rats perfused with 1.5 µM of zofenopril, and STZ-treated diabetic animals (DM) were diabetic animals perfused with 1.5 µM of zofenopril 4 weeks after the induction of diabetes. Our results demonstrated that diabetic rats are characterized by a depressed cardiac performance and that oxidative markers are related to alterations in cardiac function in rats with 4 weeks of STZ-induced diabetes. Additionally, the use of zofenopril as a monotherapy slightly diminished cardiac damage induced by chronic hyperglycaemia. However, long-term follow-up intervention trials are necessary to fully demonstrate the benefit of zofenopril in this context. A challenge for future investigations will be to identify the effects of chronic administration or combination therapy with angiotensin-converting enzyme inhibitors in various models of diabetes.     

Effect of U50,488H, a κ-opioid receptor agonist on myocardial α-and β-myosin heavy chain expression and oxidative stress associated with isoproterenol-induced cardiac hypertrophy in rat

Both oxidative stress and β-MHC expression are associated with pathological cardiac hypertrophy. β-adrenergic receptor stimulation plays an important role in cardiac hypertrophy. Recent studies have reported a negative interplay between opioid receptors and adrenoceptors in heart. This study investigated the effect of U50,488H (a selective κ-opioid receptor agonist) on myocardial oxidative stress and α- and β-MHC expression in isoproterenol-induced cardiac hypertrophy. Male Wistar rats were administered normal saline (control), isoproterenol (ISO) (5 mg/kg BW s.c. OD), and isoproterenol with U50,488H (0.4 and 0.6 mg/kg BW, i.p. OD) for 14 days. In a separate group, nor-binaltorphimine (nor-BNI) (0.5 mg/kg, BW, i.p.) (κ-receptor antagonist) was administered along with ISO and U50,488H. ISO administration caused significant increase in left ventricular (LV) wall thicknesses, LV mass in echocardiography, heart weight to body weight ratio, and myocyte size as compared to control. Both the doses of U50,488H offered significant protection against these changes. The higher dose of U50,488H significantly prevented ISO-induced increase in myocardial lipid peroxidation and depletion of myocardial antioxidants (glutathione, superoxide dismutase, and catalase), while a similar trend (although not significant) was observed with the lower dose also. ISO-induced myocardial fibrosis was also significantly attenuated by both the doses of U50,488H. Isoproterenol-induced β-MHC expression in the hypertrophied heart was not altered by either doses of U50,488H, however, the latter prevented the loss of myocardial α-MHC expression. All these effects of U50,488H were blocked by nor-BNI. This study provides the evidence that U50,488H reduced oxidative stress and preserved expression of α-MHC in isoproterenol-induced cardiac hypertrophy.     

Post-infarct sleep disruption and its relation to cardiac remodeling in a rat model of myocardial infarction

Sleep disruption after myocardial infarction (MI) by affecting ubiquitin–proteasome system (UPS) is thought to contribute to myocardial remodeling and progressive worsening of cardiac function. The aim of current study was to test the hypothesis about the increased risk of developing heart failure due to experience of sleep restriction (SR) after MI. Male Wistar rats (n = 40) were randomly assigned to four experimental groups: (1) Sham, (2) MI, (3) MI and SR (MI + SR) (4) Sham and SR (Sham + SR). MI was induced by permanent ligation of left anterior descending coronary artery. Twenty-four hours after surgery, animals were subjected to chronic SR paradigm. Blood sampling was performed at days 1, 8 and 21 after MI for determination of serum levels of creatine kinase-MB (CK-MB), corticosterone, malondialdehyde (MDA) and nitric oxide (NO). Finally, at 21?days after MI, echocardiographic parameters and expression of MuRF1, MaFBx, A20, eNOS, iNOS and NF-kB in the heart were evaluated. We used H&;E staining to detect myocardial hypertrophy. We found out that post infarct SR increased corticosterone levels. Our results highlighted deteriorating effects of post-MI SR on NO production, oxidative stress, and echocardiographic indexes (p < 0.05). Moreover, its detrimental effects on myocardial damage were confirmed by overexpression of MuRF1, MaFBx, iNOS and NF-kB (p < 0.001) in left ventricle and downregulation of A20 and eNOS (p < 0.05). Furthermore, histological examination revealed that experience of SR after MI increased myocardial diameter as compared to Sham subjects (p < 0.05). Our data suggest that SR after MI leads to an enlargement of the heart within 21?days, marked by an increase in oxidative stress and NO production as well as an imbalance in UPS that ultimately results in cardiac dysfunction and heart failure.     

Oxidative stress and altered antioxidant defenses in children with acute exacerbation of atopic dermatitis

The underlying mechanisms of skin inflammation in atopic dermatitis (AD) are not completely understood. The purpose of the present study was to examine the involvement of oxidative stress and antioxidant defenses in children with acute exacerbation of AD. We studied 13 children who were hospitalized for acute exacerbation of AD with purulent skin infection by Staphylococcal aureus (age, 1.5 to 10.0 years), and 28 age-matched healthy subjects (controls). Urine samples obtained from the patients on admission, on 2nd and 7th-9th hospital days, as well as from the controls were analyzed for 8-hydroxy-2'-deoxyguanosine (8-OHdG) (a marker of oxidative DNA damage), acrolein-lysine adducts (a marker of lipid peroxidation), bilirubin oxidative metabolites (BOM) (a marker of antioxidant activity of bilirubin under oxidative stress) and nitrite/nitrate (NO(x)(-)) (a marker of endogenous nitric oxide production). Of these, urinary concentrations of 8-OHdG, acrolein-lysine adducts and BOM, but not NO(x)(-), were significantly higher in AD children on admission than those in control subjects. Response to treatment was associated with significant falls in the concentrations of 8-OHdG and acrolein-lysine adducts. Urinary concentrations of acrolein-lysine adducts, but not 8-OHdG, were still significantly higher in AD patients on the 7th-9th hospital day relative to the control. Urinary BOM remained almost constant and significantly high in AD children during hospitalization. Our findings indicate that oxidative stress and altered antioxidant defenses are involved in the pathophysiology of acute exacerbation of AD, and that suppression of oxidative stress might be a potentially useful strategy for the treatment of AD.     

Determination of Micronutrients and Oxidative Stress Status in the Blood of STZ-Induced Experimental Diabetic Rat Models

This study aims to research the effect of streptozotocin (STZ) at different doses on the serum micronutrients and oxidative stress status in diabetic rat models. Twenty male rats averaged 250 g and 3–4 months old were used as experimental models. They were put in four groups composed of five rats each. Diabetic was induced by administering STZ 55 and 65 mg/kg intraperitonally. The serum micronutrients including minerals and vitamins (Cu, Zn, Mg, Fe, vitamins D, E, and C) and oxidative stress (malondialdehyde, MDA) were determined. Cu, Zn, and Vitamin D3 levels were found to increase significantly in STZ groups (p < 0.005). Retinol levels decreased significantly in STZ groups (p < 0.005). In the groups administered 55 mg/kg STZ ferrum and vitamin C levels were found significantly lower than the other groups (p < 0.005). In the group given 65 mg/kg STZ α-tocopherol levels were highest (p < 0.005) among other groups. There was not any difference between the groups for MDA, Cu/Zn, and Mg. For both doses, oxidative stress status was not significantly affected within 48 h of the application, however, some micronutritents were affected significantly.     

The Effect of Different Oral Doses of Hydroalcoholic Extract of Silymarin on the Blood Oxidative Stress Indicators in Streptozotocin Induced Diabetic Rats

The effect of oral administration of different doses of hydroalcoholic extract of silymarin on body weight, glucose concentration and indicators of oxidative stress superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and malondialdehyde (MDA) was investigated in the present study. Fifty adult male Wistar rats were used. The animals were divided into five groups and oral route of administration was used in control group (0.9 %, NaCl), control group patients (0.9 %, NaCl), diabetic group (100 mg/kg, silymarin), diabetic group (125 mg/kg, silymarin), diabetic group (250 mg/kg, silymarin) for 14 days with gavage. Diabetes was induced by a single injection of streptozotocin (45 mg/kg, i.p.). Before and 3 days after injection, and at 7 and 14 days of treatment, the fasting glucose level and weight were measured. At the end of 14 days, animals were anesthetized with ether and blood samples were taken by heart puncture and were analyzed for oxidative stress indicators. The results showed that hydroalcoholic extract of silymarin can increase the average body weight and decrease glucose and, at the end of 14 days, decrease MDA level and increase the level of antioxidant enzymes (SOD, GPX, CAT) in red blood cells in a dose-dependent manner (P < 0.05). In conclusion, the hydroalcoholic extract of silymarin has an overall beneficial effect on body weight, glucose level and oxidative stress. Therefore, silymarin may reduce oxidative stress via increasing antioxidant enzyme activity.     

Effects of Extremely Low-Frequency Magnetic Field on Caspase Activities and Oxidative Stress Values in Rat Brain

This study was aimed to investigate the effect of extremely low-frequency magnetic field (ELF-MF) on apoptosis and oxidative stress values in the brain of rat. Rats were exposed to 100 and 500 µT ELF-MF, which are the safety standards of public and occupational exposure for 2 h/day for 10 months. Brain tissues were immunohistochemically stained for the active (cleaved) caspase-3 in order to measure the apoptotic index by a semi-quantitative scoring system. In addition, the levels of catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO), total antioxidative capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) were measured in rat brain. Final score of apoptosis and MPO activity were not significantly different between the groups. CAT activity decreased in both exposure groups (p?<?0.05), while TAC was found to be lower in ELF 500 group than those in ELF-100 and sham groups (p?<?0.05). MDA, TOS, and OSI values were found to be higher in ELF-500 group than those in ELF-100 and sham groups (p?<?0.05). In conclusion, apoptosis was not changed by long-term ELF-MF exposure, while both 100 and 500 µT ELF-MF exposure induced toxic effect in the rat brain by increasing oxidative stress and diminishing antioxidant defense system.     

Characterization of Clostridium thermocellum Isolates Grown on Cellulose and Sugarcane Bagasse

Although plant cell walls may be degraded by microbial free enzymes, many bacteria degrade cellulose via enzyme complexes called cellulosomes. The study of the structures and mechanisms of these large macromolecular complexes is an active and ongoing research topic, with the goal of developing methods to improve lignocellulosic biomass conversion using cellulosomes. The aim of the present work was to evaluate and characterize the holocellulolytic activities produced by two new isolates (ISO1 and ISO2) of the spore-forming thermophilic anaerobic bacterium Clostridium thermocellum, during growth on crystalline cellulose and sugarcane bagasse, in comparison with activities obtained from the C. thermocellum strain CthJW. The pH and temperature values for optimal growth of the isolates were pH 7 and 60 °C, respectively. The isolates produced cellulolytic, xylanolytic, and pectinolytic activities when cultured on crystalline cellulose or sugarcane bagasse, which have never been used previously as the sole carbon source for these bacteria. The profiles of secreted proteins for these isolates, ISO1 and ISO2, were quite different from those obtained for the standard strain CthJW and from each other, as shown by 2D gel electrophoresis maps, and these profiles also depend on the carbon source used. Different protein isoforms were also detected in the maps for all growth conditions and bacterial strains. MALDI-TOF mass spectrometry was used to identify the differentially expressed proteins for ISO1 and ISO2 under growth in the presence of cellulose as carbon source. Twenty-five differentially expressed spots were identified and grouped into 8 functional categories: metabolism (20 %), motor function (20 %), protein synthesis (12 %), oxidative stress (16 %), secretory pathway (12 %), cellulose hydrolysis (4 %), protein folding (4 %), and defense (12 %). Spots 200 and 197, identified as a glycosyl hydrolase family member 9 and as a chaperone GroEL, respectively, were detected for all isolates and are potentially related to cellulosome architecture.     

Size-Dependent Neurotoxicity of Aluminum Oxide Particles: a Comparison Between Nano- and Micrometer Size on the Basis of Mitochondrial Oxidative Damage

Aluminum nanoparticles (AlNPs) are among the most abundantly produced nanosized particles in the market. There is limited information about the potential harmful effects of aluminum oxide due to its particle size on human health. Considering the toxic effects of Al on brain as its target tissue, in this study, the toxicity of nanoparticles, microparticles, and ionic forms of Al on rat brain and isolated mitochondria was evaluated. Sixty male Wistar rats were divided into ten groups (six rats each), in which group I was the control, and the other groups were administered different doses of Al nanoparticles, Al microparticles (AlMP), and Al ionic forms (2, 4, and 8 mg/kg, i.p.) for 28 days. After 24 h, the animals were killed, brain tissue was separated, the mitochondrial fraction was isolated, and oxidative stress markers were measured. Also, mitochondrial function was assayed by MTT test. The results showed that all forms of Al particles induced ROS formation, lipid peroxidation, protein oxidation, glutathione depletion, mitochondrial dysfunction, and gait abnormalities in a dose-dependent manner. In addition, Al particles decreased mitochondrial membrane potential. These data indicated that oxidative stress might contribute to the toxicity effects of Al. Comparison of oxidative stress markers between all forms of Al revealed that the toxic effect of AlNP on brain tissue was substantially more than that caused by AlMP and bulk form. This study showed more neurotoxicity of AlNPs compared to other forms on brain oxidative damage that probably is due to more penetration into the brain.     

Astragaloside IV prevents acute kidney injury in two rodent models by inhibiting oxidative stress and apoptosis pathways

Oxidative stress and apoptosis play key role in the pathogenesis of acute kidney injury (AKI). We hypothesize that Astragaloside IV(AS-IV) prevents AKI through inhibiting oxidative stress and apoptosis. The rats were divided into sham control, saline-,vehicle-, or AS-IV-treated groups. AS-IV (20 mg/kg) was orally administered once daily to the rats for 7 consecutive days before terminating the experiments. In ischemia-induced AKI model, experimental rats were subjected to bilateral clamping of the renal arteries for 45 min, followed by reperfusion for 24 h. In contrast-induced AKI model, iopamidol (2.9 g iodine/kg) was administered intravenously into the rats. Renal function, histopathology, oxidative stress and apoptosis were evaluated in these models. Pretreatment with AS-IV significantly decreased blood urea nitrogen, serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin levels, as well as urinary kidney injury molecule-1 level and tubular injury. AS-IV also reduced oxidative stress and tubular cell apoptosis. The p38 mitogen-activated protein kinase phosphorylation and caspase-3 activity were elevated in kidney tissues from AKI rats, accompanied by an increase in Bax expression and a decrease in Bcl-2 expression at mRNA and protein levels. These changes were prevented by AS-IV pretreatment. Therefore, AS-IV can be developed as a novel therapeutic approach to prevent AKI through targeting inhibition of oxidative stress and apoptosis pathways.     

Obtusifolin Treatment Improves Hyperlipidemia and Hyperglycemia: Possible Mechanism Involving Oxidative Stress

Clinical research has confirmed the efficacy of several plant extracts in the modulation of oxidative stress associated with hyperlipidemia and hyperglycemia induced by obesity and diabetes. Findings indicate that obtusifolin has antioxidant properties. The aim of this study was to evaluate the possible protective effects of obtusifolin against oxidative damage in diabetic hyperlipidemia and hyperglycemia. In this study, the rats were divided into the following groups with eight animals in each: control, untreated diabetic, three obtusifolin (10, 30, and 90 mg/kg/day)-treated diabetic groups. Diabetes was induced by streptozotocin (STZ) in rats. STZ was injected intraperitoneally at a single dose of 60 mg/kg for diabetes induction. Obtusifolin (intraperitoneal injection) was administered 3 days after STZ administration; these injections were continued to the end of the study (4 weeks). At the end of the 4-week period, blood was drawn for biochemical assays. In order to determine the changes of cellular antioxidant defense systems, antioxidant enzymes including glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities were measured in serum. Moreover, we also measured serum nitric oxide (NO) and serum malondialdehyde (MDA) levels, markers of lipid peroxidation. STZ-induced diabetes caused an elevation (P < 0.001) of blood glucose, MDA, NO, total lipids, triglycerides and cholesterol, with reduction of GSH level and CAT and SOD activities. The results indicated that the significant elevation in the blood glucose, MDA, NO, total lipids, triglycerides and cholesterol; also the reduction of glutathione level and CAT and SOD activity were ameliorated in the obtusifolin-treated diabetic groups compared with the untreated groups, in a dose-dependent manner (P < 0.05, P < 0.01, P < 0.001). These results suggest that obtusifolin has antioxidant properties and improves chemically induced diabetes and its complications by modulation of oxidative stress.     

Aqueous extract of black tea (Camellia sinensis) prevents ethanol+cholecystokinin-induced pancreatitis in a rat model

Black Tea Extract (BTE), a phytocompound has been attributed with a plethora of health-promoting actions. We have previously demonstrated that BTE inhibits chronic hepatitis in a rat model induced with high-fat and ethanol (EtOH). This study reports that BTE prevents altered pancreatic acinar cell functions, oxidative stress, inflammatory changes and DNA damage in the EtOH+cholecystokinin (CCK)-induced model of pancreatitis. The EtOH+CCK model rats were administered with BTE, and were examined the activity of pancreatic digestive enzymes (amylase and lipase), proinflammatory cytokines (IL-6 and TNF-alpha), oxidative and antioxidative enzymes (nitric oxide, NO; malondialdehyde, MDA; superoxide dismutase, SOD; catalase, CAT), antioxidant level (glutathione, GSH), histopathological changes and the integrity of genomic DNA. Results show that because of chronic EtOH treatment, serum level of amylase and lipase (two biomarkers for pancreatitis) and pancreatic levels of MDA and NO (two biomarkers of oxidative stress) increased significantly, which could be effectively blunted by BTE. BTE could normalize EtOH+CCK-induced suppressed activities of SOD and CAT, and GSH content of pancreatic tissue. Also, histopathological and inflammatory changes during EtOH+CCK-induced pancreatitis could be blunted by BTE. Furthermore, BTE could effectively reduce EtOH+CCK-induced increase in DNA fragmentation and damage. These findings suggest that BTE prevents pancreatitis caused by chronic EtOH+CCK toxicity presumably by enhancing antioxidant, anti-inflammatory and antiapoptotic activity in rats.