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Endogenous Antioxidant (endogenous + antioxidant)
Selected AbstractsEffect of Exogenous and Endogenous Antioxidants on 3-Nitropionic Acid-Inducedin vivo Oxidative Stress and Striatal LesionsJOURNAL OF NEUROCHEMISTRY, Issue 4 2000Insights into Huntington's Disease Abstract: 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of complex II in the mitochondria. 3-NP toxicity has gained acceptance as an animal model of Huntington's disease (HD). In the present study, we confirmed that rats injected with 3-NP (20 mg/kg, i.p., daily for 4 days) exhibit increased oxidative stress in both striatum and cortical synaptosomes as well as lesions in the striatum. Synaptosomal membrane proteins from rats injected with 3-NP exhibited a decrease in W/S ratio, the relevant electron paramagnetic resonance (EPR) parameter used to determine levels of protein oxidation, and western blot analysis for protein carbonyls revealed direct evidence of increased synaptosomal protein oxidation. Treatment of rats with the brain-accessible free radical spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N -oxide (DEPMPO; 30 mg/kg, i.p., daily 2 h before 3-NP injection) or with N -acetylcysteine (NAC; 100 mg/kg, i.p., daily 2 h before 3-NP injection), a known glutathione precursor, before 3-NP treatments protects against oxidative damage induced by 3-NP as measured by EPR and western blot analysis for protein carbonyls. Furthermore, both DEMPMPO and NAC treatments before 3-NP administration significantly reduce striatal lesion volumes. These data suggest oxidative damage is a prerequisite for striatal lesion formation and that antioxidant treatment may be a useful therapeutic strategy against 3-NP neurotoxicity and perhaps against HD as well. [source] The Role of Neurotrophic Factors, Apoptosis-Related Proteins, and Endogenous Antioxidants in the Differential Temporal Vulnerability of Neonatal Cerebellum to EthanolALCOHOLISM, Issue 4 2003Marieta Barrow Heaton Background: Ethanol produces abnormalities in the developing nervous system, with certain regions being vulnerable during well-defined periods. Neonatal rodent cerebellum is particularly susceptible to ethanol during the early postnatal period [on postnatal days 4-5 (P4-5)], while this region is resistant to ethanol at a slightly later time (P7-9). We assessed basal levels of several substances which may be involved in differential temporal ethanol vulnerability in neonatal cerebellum, and analyzed alterations in these substances after early ethanol exposure. Methods: Assessments were made of neurotrophic factors nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4; apoptosis-related proteins Bcl-2, Bcl-xl, Bax, Bcl-xs, Bad, phosphorylated-Bad, phosphorylated-Akt, and phosphorylated-c-Jun N-terminal kinase; and the antioxidants superoxide dismutase, glutathione reductase, and catalase. These analyses quantified basal levels (in controls), and sequential changes following acute ethanol exposure at the vulnerable and resistant cerebellar periods (P4, P7). Results: Comparisons of basal levels of the molecules assessed between P4 and P7 revealed higher levels of total proapoptotic Bad at p4, higher levels of the protective pAkt kinase at P7, and lower levels of proapoptotic pJNK at P7. Other basal levels did not differ. While ethanol-mediated alterations were found at both ages favoring both apoptosis and survival, the apoptosis-promoting changes produced on P4 exceeded those on P7, and most occurred within the first 2 hr after exposure, a critical survival/death period. The number of alterations favoring survival were similar at the two ages, but at P7 most occurred within the first 2 hr after exposure, possibly acting in a protective manner. Conclusions: Differential temporal vulnerability to ethanol in the neonatal cerebellum appears to be paralleled by cellular alterations in neurotrophic factors, apoptosis-regulatory proteins, and/or antioxidant activities which generally favor apoptosis at the most sensitive age and survival at the resistant age. [source] Changes in antioxidant defense status in response to cisplatin and 5-FU in esophageal carcinomaDISEASES OF THE ESOPHAGUS, Issue 2 2008T. Kaur SUMMARY., The ability of reactive oxygen species to induce cellular damage and to cause cell death opens the possibility of exploiting this property in the treatment of esophageal cancer through a free radical mediated mechanism. The present study was carried out with the aim of evaluating the changes in the antioxidant defense status in esophageal cancer patients treated without and with neoadjuvant therapy (NAT). Forty surgically resected tissue specimens from tumors, tissue adjoining the tumors and paired macroscopically normal mucosa were obtained from esophageal cancer patients treated with or without chemo-radiotherapy. An evaluation of antioxidant defense system in the normal, adjoining and tumor esophageal tissues in response to NAT revealed decreased catalase activity in tumor and adjoining tissues as compared to their respective normal tissue levels. Similarly, decreased superoxide dismutase activity was observed in tumor tissue in response to NAT. In both the treatment groups (with and without NAT), no significant change was observed in the enzyme activity of glutathione reductase in the normal, adjoining and tumor tissues. Enhanced glutathione peroxidase activity was found in tumor tissue, as compared to the adjoining and paired normal tissue of patients after NAT. Estimation of reduced glutathione (GSH) levels showed a significant decline in GSH levels in esophageal tumors after NAT. Depletion of GSH, an endogenous antioxidant, would elevate drug sensitivity and might predispose neoplastic cells to apoptosis in response to NAT. The antioxidant enzymes in the esophageal carcinoma thus may play an important role in influencing the final outcome upon NAT course. [source] Protection of estrogens against the progression of chronic liver diseaseHEPATOLOGY RESEARCH, Issue 4 2007Ichiro Shimizu Hepatitis C virus infections are recognized as a major causative factor of chronic liver disease. A characteristic feature of chronic hepatitis C, alcoholic liver disease and non-alcoholic fatty liver disease is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which, in turn, activates hepatic stellate cells (HSCs). HSCs are also thought to be the primary target cells for inflammatory and oxidative stimuli, and to produce extracellular matrix components. Based on available clinical information, chronic hepatitis C appears to progress more rapidly in men than in women, and cirrhosis is predominately a disease of men and postmenopausal women. Estradiol is a potent endogenous antioxidant. Hepatic steatosis was reported to become evident in an aromatase-deficient mouse and was diminished in animals after treatment with estradiol. Our previous studies showed that estradiol suppressed hepatic fibrosis in animal models, and attenuated HSC activation by suppressing the generation of reactive oxygen species in primary cultures. Variant estrogen receptors were found to be expressed to a greater extent in male patients with chronic liver disease than in female subjects. A better understanding of the basic mechanisms underlying the gender-associated differences observed in the progression of chronic liver disease would provide valuable information relative to the search for effective antifibrogenic therapies. [source] Cardiotoxicity of doxorubicin/paclitaxel combination in rats: Effect of sequence and timing of administrationJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2004Sherif Y. Saad Abstract The higher incidence of cardiotoxicity of doxorubicin (DOX)/paclitaxel (PTX) combination compared with DOX alone remains to be a major obstacle against effective chemotherapeutic treatment. We investigated the effect of sequence and time interval between administration of both drugs on the severity of cardiotoxicity of the combination. Male Wistar rats were divided into seven groups. DOX was administeded intraperitoneally (ip) at a single dose of 5 mg kg,1 every other 2 days, 2 doses per week for a total cumulative dose of 20 mg kg,1. PTX was administered by an ip route at a dose of 20 mg kg,1 every other 2 days. Both drugs were injected either alone or sequentially in combination. In one case, DOX preceded PTX by 30 min and 24 h and in the other case, PTX preceded DOX by 30 min and 24 h. Cardiotoxicity was evaluated by both biochemical and histopathological examination, 48 h after the last DOX dose. DOX-induced cardiotoxicity was manifested by abnormal biochemical changes including marked increases in serum creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), and aspartate aminotransferase (AST) activity levels. Myocardial tissue from DOX-treated rats showed significant increases in malondialdehyde (MDA) production and total nitrate/nitrite (NOx) levels, parallel with depletion of "endogenous antioxidant reserve," including GSH contents and GSH-Px activity level. PTX treatment produced significant changes in the biochemical parameters measured by a lower magnitude than those changes produced by DOX alone. Combination of both drugs resulted in aggravation of DOX-induced cardiotoxicity regardless the sequence and time interval between administration of either drug. Administration of PTX 30 min and 24 h after DOX treatment showed exaggeration of combination-induced cardiotoxicity compared with the reverse sequence. This exacerbation was manifested by much more pronounced changes in serum and cardiac tissue parameters measured. Histopathological examination of ventricles of rat's heart revealed that DOX treatment produced myo-cytolysis and myocardial necrosis. Administration of PTX following DOX treatment showed extensive myocardial necrosis compared with those rats treated with either DOX alone or the reverse sequence of administration. Moreover, rats treated with PTX 24 h after DOX treatment showed exaggeration of the combination-induced cardiotoxicity. In conclusion, PTX might synergistically aggravate DOX-induced cardiotoxicity. The effect might be much more pronounced with those rats treated with PTX 24 h after DOX treatment. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:78,86, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20012 [source] Changes in the levels of glutathione after cellular and cutaneous damage induced by squalene monohydroperoxideJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2001Katsuyoshi Chiba Abstract Squalene monohydroperoxide (Sq-OOH), the initial product of ultraviolet-peroxidated squalene, was used to investigate the effect of peroxidative challenge upon the glutathione contents in rabbit ear skin and primary-cultured fibroblasts derived from rabbit ear skin. The cellular reduced glutathione (GSH) contents decreased during 30-minute incubations in vitro with Sq-OOH, and oxidized glutathione (GSSG) was formed concomitantly, indicating that Sq-OOH had a potential for GSH-depleting activity in vitro. When Sq-OOH was applied topically to the skin in vivo, only GSSG contents increased significantly within 30 minutes. Moreover, pretreatment with the GSH depletors, DL -buthionine sulfoximine (BSO) and diethyl maleate (DEM), could potentiate the cytotoxicity and comedogenicity induced by Sq-OOH. These findings suggest that the endogenous antioxidant, glutathione, is quite sensitive to Sq-OOH and may be an important material for protecting cells and/or tissues against the oxidative stress induced by Sq-OOH treatment. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:150,158, 2001 [source] ,-glutamylcysteine ethyl ester-induced up-regulation of glutathione protects neurons against A,(1,42)-mediated oxidative stress and neurotoxicity: Implications for Alzheimer's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2005Debra Boyd-Kimball Abstract Glutathione (GSH) is an important endogenous antioxidant found in millimolar concentrations in the brain. GSH levels have been shown to decrease with aging. Alzheimer's disease (AD) is a neurodegenerative disorder associated with aging and oxidative stress. A,(1,42) has been shown to induce oxidative stress and has been proposed to play a central role in the oxidative damage detected in AD brain. It has been shown that administration of ,-glutamylcysteine ethyl ester (GCEE) increases cellular levels of GSH, circumventing the regulation of GSH biosynthesis by providing the limiting substrate. In this study, we evaluated the protective role of up-regulation of GSH by GCEE against the oxidative and neurotoxic effects of A,(1,42) in primary neuronal culture. Addition of GCEE to neurons led to an elevated mean cellular GSH level compared with untreated control. Inhibition of ,-glutamylcysteine synthetase by buthionine sulfoximine (BSO) led to a 98% decrease in total cellular GSH compared with control, which was returned to control levels by addition of GCEE. Taken together, these results suggest that GCEE up-regulates cellular GSH levels which, in turn, protects neurons against protein oxidation, loss of mitochondrial function, and DNA fragmentation induced by A,(1,42). These results are consistent with the notion that up-regulation of GSH by GCEE may play a viable protective role in the oxidative and neurotoxicity induced by A,(1,42) in AD brain. © 2005 Wiley-Liss, Inc. [source] Neuroprotective effects of Triticum aestivum L. against ,-Amyloid-induced cell death and memory impairmentsPHYTOTHERAPY RESEARCH, Issue 1 2010Jung-Hee Jang Abstract ,-Amyloid (A,) is a key component of senile plaques, neuropathological hallmarks of Alzheimer's disease (AD) and has been reported to induce cell death via oxidative stress. This study investigated the protective effects of Triticum aestivum L. (TAL) on A,-induced apoptosis in SH-SY5Y cells and cognitive dysfunctions in Sprague-Dawley (SD) rats. Cells treated with A, exhibited decreased viability and apoptotic features, such as DNA fragmentation, alterations in mitochondria and an increased Bax/Bcl-2 ratio, which were attenuated by TAL extract (TALE) pretreatment. To elucidate the neuroprotective mechanisms of TALE, the study examined A,-induced oxidative stress and cellular defense. TALE pretreatment suppressed A,-increased intracellular accumulation of reactive oxygen species (ROS) via up-regulation of glutathione, an essential endogenous antioxidant. To further verify the effect of TALE on memory impairments, A, or scopolamine was injected in SD rats and a water maze task conducted as a spatial memory test. A, or scopolamine treatment increased the time taken to find the platform during training trials, which was decreased by TALE pretreatment. Furthermore, one of the active components of TALE, total dietary fiber also effectively inhibited A,-induced cytotoxicity and scopolamine-caused memory deficits. These results suggest that TALE may have preventive and/or therapeutic potential in the management of AD. Copyright © 2009 John Wiley & Sons, Ltd. [source] Pharmacological effects of fermented red pepperPHYTOTHERAPY RESEARCH, Issue 11 2004Y. M. Choi Abstract The pharmacological effects were investigated of fermented red pepper (HF-S), which consisted of 14.7% carbohydrate, 1.5% lipid, 4.9% protein, 0.3% ash, 78.2% moisture content, with 0.15% capsaicin and 0.06% dihydrocapsaicin. Oral administration of 0.25 mL HF-S for 3 weeks produced signi,cant changes of the perirenal fat pad weight compared with the HF-control group, suggesting a suppressive effect on lipid accumulation and a signi,cant decrease in the risk of arteriosclerosis. The HF-S (0.25 mL) group also showed a lower plasma TG, TC level and atherogenic index than that of the HF-control. In addition, the HF-S (0.25 mL) group showed a marked increase in the production of glutathione, which is the major endogenous antioxidant, and a decrease in the production of lipid peroxide as the product of chemical damage by oxygen free radicals. It is assumed that the effect of HF-S might relate to high glutathione production on the suppression of lipid peroxidation. HF-S stimulated not only the proliferation of macrophages (as high as the positive control, LPS at 1000 µg/mL) but also mitogenic activity (1.2-fold of LPS at 100 µg/mL). Copyright © 2004 John Wiley & Sons, Ltd. [source] The in vitro effects of melatonin on human sperm function and its scavenging activities on NO and ROSANDROLOGIA, Issue 2 2010S. S. Du Plessis Summary Various systems of antioxidants exist endogenously in the body to help protect it against free radical damage by scavenging excessive ROS and RNS. Melatonin, a hormone secreted by the pineal gland, and responsible for controlling the circadian rhythm, is one such endogenous antioxidant. Melatonin has been reported to be present in human seminal fluid, but its antioxidant activities in semen are rather contradictory. This study aimed at establishing the effects of melatonin treatment on human spermatozoa. Spermatozoa were incubated with 2 mm melatonin (120 min, 37 °C, 5% CO2) after which motility parameters were measured by computer aided motility analysis, while cell viability (PI), intracellular NO (DAF-2/DA) and ROS (DCFH-DA) were assessed using flow cytometry. In vitro melatonin treated samples (n = 12) showed a significantly higher percentage of motile, progressive motile and rapid cells, while simultaneously reducing the number of nonviable spermatozoa when compared with the control. Endogenous NO was significantly decreased, but no effect was observed on ROS levels. From these results, it can be concluded that melatonin was able to directly or indirectly scavenge NO, as indicated by the reduction in 4,5-diaminofluorescein-2/diacetate fluorescence. Future studies will indicate whether melatonin treatment during sperm preparation techniques could protect spermatozoa from excessive NO production. [source] Role of haem oxygenase-1 in microbial host defenceCELLULAR MICROBIOLOGY, Issue 2 2009Su Wol Chung Summary Haem oxygenase (HO)-1 is a cytoprotective enzyme that plays a critical role in defending the body against oxidant-induced injury during inflammatory processes. HO catalydes the degradation of haem to carbon monoxide (CO), biliverdin and ferrous iron. Biliverdin is converted to bilirubin, a potent endogenous antioxidant. CO has a number of biological functions, including anti-inflammatory properties. In various models of disease, HO-1 is known to play a critical role by ameliorating the pathological consequences of injury. In many of these models, the beneficial effects of HO-1 and its products of haem catabolism are by suppressing an inflammatory response. However, when investigating diseases due to microbial infections, inhibition of the inflammatory response could disrupt the ability of the immune system to eradicate an invading pathogen. Thus, questions remain regarding the role of HO-1 in microbial host defence. This microreview will address our present understanding of HO-1 and its functional significance in a variety of microbial infections. [source] Glutathione, vitamin E and oxidative stress in coronary artery disease: relevance of age and genderEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2009V. Cavalca Abstract Background, Observational studies suggest that low levels of antioxidants are associated with high risk for coronary artery disease (CAD). We investigated whether the biomarkers of oxidative balance undergo the same modifications in all CAD patient groups, regardless of gender and age. Materials and methods, One hundred sixty-eight CAD patients and 107 healthy controls were assayed for plasma levels of reduced glutathione (GSH), ,- and ,-tocopherol (,- and ,-T) as endogenous antioxidants. A damage score (DS), representative of oxidative stress status, was calculated. ancova models were used to test the association between antioxidants, DS and CAD and its modulation by age and gender. Results, The DS was higher in CAD than in controls. GSH levels, were lower in CAD patients (mean ± SEM: 57·61 ± 1·87 ,mol 10 g,1 haemoglobin vs. 68·55 ± 2·23 in controls, P < 0·0006) in males and in older subjects. Levels of other antioxidants exhibited a complex pattern. Overall, no difference was found in ,- and ,-T contents between CAD and controls, but lower ,-T values were observed in CAD females. A significant interaction between CAD status and gender was observed (P = 0·003). Conclusions, Our study shows that the involvement of antioxidants in CAD is related to patients' characteristics. These findings may be relevant in planning antioxidant therapies. [source] Lipid damage in farmed rainbow trout (Oncorhynchus mykiss) after slaughtering and chilled storageEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 12 2008Jaime Ortiz Abstract The flow ice system including ozone (OFI condition) was tested for slaughtering and storage (up to 16,days) of farmed rainbow trout (Oncorhynchus mykiss). Lipid damage analyses were carried out and compared to sensory acceptance and instrumental colour changes. Comparison to individuals processed with the flow ice system in the absence of ozone (FI condition) was undertaken. Rainbow trout slaughtered and chilled under FI and OFI conditions showed a low lipid damage development, according to lipid oxidation and hydrolysis events and lipid composition (polyunsaturated fatty acids, phospholipids and endogenous antioxidants) changes. Additionally, both icing conditions led to largely good quality and shelf life times and to the absence of changes in colour properties. It is concluded that flow ice as such, or including the presence of ozone, can be considered as ideal strategy to be employed as slaughtering and storage system during the commercialisation of the actual farmed species. The ozone presence has shown some profitable effects as leading to an extended shelf life time by quality retention of several sensory parameters; in contrast, some negligible negative effects could be observed on the secondary and tertiary lipid oxidation development. However, the oxidation values reached by individuals kept under OFI conditions cannot be considered as particularly high. [source] Ischemia,reperfusion injury: assessment and treatment, part IIJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2004DACVECC, Maureen McMichael DVM Abstract Objective: To review the current scientific literature on ischemia,reperfusion (IR) injury in both human and veterinary medicine and to describe the assessment of IR injury, the available testing methods, and the options available for treatment. Data sources: Data sources include scientific reviews and original research publications in both human and veterinary medicine. Summary: The assessment of IR injury includes measuring products formed by the reaction of reactive oxygen species (ROS) with biological membranes, measuring levels of endogenous antioxidants, and measuring ROS themselves. Testing depends on the laboratory used, the test method chosen, the sample submitted (i.e., plasma, urine, tissue, etc.), and the timing of the test in relation to sample collection. For this reason, testing is not standardized and pharmacological data on antioxidant effectiveness are not available. Antioxidants and drugs tested have included single agents as well as ,cocktails' consisting of several agents working at different key points in the injury cascade. Conclusions: There are several new testing methods as well as new strategies for attempting to ameliorate the damage inflicted upon reperfusion and this article is intended as a review of the assessment and treatment of IR injury. [source] Aucubin prevents loss of hippocampal neurons and regulates antioxidative activity in diabetic encephalopathy ratsPHYTOTHERAPY RESEARCH, Issue 7 2009Hong-Yu Xue Abstract In this study, the neuroprotection of aucubin and its mechanism were evaluated in the rat model of diabetic encephalopathy. Diabetes mellitus (DM) rats were stratified by cognitive capability (CC), and assigned to four treatment groups for aucubin treatment (doses of 0, 1, 5 or 10 mg/kg aucubin), with a further two groups of non-DM rats ranked by CC as controls for aucubin (doses of 0 or 5 mg/kg aucubin). Neuroprotection was estimated by the indexes of behavior and histology. Behavioral testing was performed in a Y-maze. The surviving neurons in CA1,CA4 and subiculum (SC) of the hippocampus were counted under a microscope. In addition, the apoptotic neurons in the CA1 of the hippocampus were also examined by using TUNEL staining. In order to clarify the mechanism of aucubin's neuroprotection, the activities of endogenous antioxidants and nitric oxide synthase (NOS) together with the content of lipid peroxide in the hippocampus were assayed. The results proved that aucubin significantly reduced the content of lipid peroxide, regulated the activities of antioxidant enzymatic and decreased the activity of NOS. All these effects indicated that aucubin was a potential neuroprotective agent and its neuroprotective effects were achieved, at least in part, by promoting endogenous antioxidant enzymatic activities. Copyright © 2009 John Wiley & Sons, Ltd. [source] Spirulina platensis protects against gentamicin-induced nephrotoxicity in ratsPHYTOTHERAPY RESEARCH, Issue 11 2008Ali Karadeniz Abstract The present study aimed to investigate the protective effect of Spirulina platensis (SP) on gentamicin sulphate (GS)-induced changes in the levels of lipid peroxidation and endogenous antioxidants in the kidney of rats. Sprague-Dawley rats were treated in separate groups as follows for 7 consecutive days: control (C), gentamicin sulphate (100 mg/kg i.p.) (GS), Spirulina platensis (1000 mg/kg orally) (SP) and Spirulina platensis (1000 mg/kg orally) plus gentamicin sulphate (100 mg/kg i.p.) (SP + GS). The degree of protection was evaluated by determining the effects of Spirulina platensis on malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX) and nitric oxide (NO), and plasma creatinine and urea levels were estimated in kidney homogenates to evaluate antioxidant activity, and the kidney was histologically examined as well. Spirulina platensis elicited significant nephroprotective activity by decreasing lipid peroxidation (MDA) and elevated the levels of GSH, SOD, GPX, NO, creatinine and urea. Furthermore, these biochemical observations were supplemented by histological examination of the rat kidneys. In conclusion, the present study indicates a very important role of reactive oxygen species (ROS) and the relation to renal dysfunction and point to the therapeutic potential of Spirulina platensis in gentamicin sulphate induced nephrotoxicity. Copyright © 2008 John Wiley & Sons, Ltd. [source] | |||||||||||||