Oxidative Stress Toxicity Research Articles

Monosodium glutamate-induced oxidative kidney damage and possible mechanisms: a mini-review.

Animal studies suggest that chronic monosodium glutamate (MSG) intake induces kidney damage by oxidative stress. However, the underlying mechanisms are still unclear, despite the growing evidence and consensus that α-ketoglutarate dehydrogenase, glutamate receptors and cystine-glutamate antiporter play an important role in up-regulation of oxidative stress in MSG-induced renal toxicity. This review summaries evidence from studies into MSG-induced renal oxidative damage, possible mechanisms and their importance from a toxicological viewpoint.

Effects of Chard (Beta Vulgaris L. Var. Cicla) on Cardiac Damage in Valproic Acid-Induced Toxicity

The aim of this study was to examine the effects of chard on valproic acid (VPA)-induced cardiac damage. Female Sprague-Dawley rats were grouped as control, chard given control (100 mg/kg/day, by gavage), VPA (500 mg/kg/day, intraperitoneally) and chard given VPA (100 mg/kg/day chard by gavage, 500 mg/kg/day VPA, intraperitoneally). The aqueous extracts of chard leaves were given 1 h prior to administration of VPA for 7 days. Malondialdehyde (MDA), total sialic acid (SA) levels and catalase (CAT) activity significantly increased in the VPA group compared with the control group (P < 0.05). Chard administration significantly decreased MDA and SA levels in the control and in the VPA groups (P < 0.05). Chard administration also significantly increased CAT activities and glutathione levels both in the control and in the VPA groups (P < 0.05). As a conclusion, chard consumption may prevent cardiac tissue from oxidative stress and inflammation in VPA-induced toxicity. Practical Applications Valproic acid (VPA) is an antiepileptic drug and has severe toxic effects in experimental animals and humans. Chard (Beta vulgaris L. var. cicla) has antioxidant, antidiabetic, antitumor and hepatoprotective effects. Its protective effects against VPA toxicity have not been fully investigated yet. According to the results of this study, chard (B. vulgaris L. var. cicla) can be used as a dietary food supplement in the epilepsy treatment. The beneficial effect of chard consumption is an important finding in a nutritional point of view as chard contains many significant bioactive constituents for a healthy diet.

Fumonisins: oxidative stress-mediated toxicity and metabolism in vivo and in vitro.

Fumonisins (FBs) are widespread Fusarium toxins commonly found as corn contaminants. FBs could cause a variety of diseases in animals and humans, such as hepatotoxic, nephrotoxic, hepatocarcinogenic and cytotoxic effects in mammals. To date, almost no review has addressed the toxicity of FBs in relation to oxidative stress and their metabolism. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a plausible mechanism for FB-induced toxicity as well as the metabolism. The present review showed that studies have been carried out over the last three decades to elucidate the production of reactive oxygen species (ROS) and oxidative stress as a result of FBs treatment and have correlated them with various types of FBs toxicity, indicating that oxidative stress plays critical roles in the toxicity of FBs. The major metabolic pathways of FBs are hydrolysis, acylation and transamination. Ceramide synthase, carboxylesterase FumD and aminotransferase FumI could degrade FB1 and FB2. The cecal microbiota of pigs and alkaline processing such as nixtamalization can also transform FB1 into metabolites. Most of the metabolites of FB1 were less toxic than FB1, except its partial (pHFB1) metabolites. Further understanding of the role of oxidative stress in FB-induced toxicity will throw new light on the use of antioxidants, scavengers of ROS, as well as on the blind spots of metabolism and the metabolizing enzymes of FBs. The present review might contribute to reveal the toxicity of FBs and help to protect against their oxidative damage.

Attenuation of Oxidative Stress and Glucose Toxicity by Lutein Loaded Nanoparticles from &lt;I&gt;Spinacia oleracea&lt;/I&gt; Leaves

Attenuation of Oxidative Stress and Glucose Toxicity by Lutein Loaded Nanoparticles from &lt;I&gt;Spinacia oleracea&lt;/I&gt; Leaves

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ±dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn2+ and albumin levels (P<0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P<0.01). qBase+ was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P<0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation.

Topical and Oral Herbal Pain Remedies

as many as 40 million Americans suffer with osteoarthritis. The most commonly recognized causes of arthritis are genetic predisposition, advancing age, obesity, trauma and “wear and tear.” However, the ‘wear and tear’ theory is probably an oversimplification, because many elderly people never develop arthritis, after years of wear and tear [1]. The degeneration of joints in all types of arthritis involves ongoing biochemical processes that negatively alter metabolism essential to maintaining healthy joints. Although conventional medical diagnostics attempt to assign patients a differential diagnosis of one specific kind of arthritis, in reality, many patients exhibit a continuum of symptoms. For example, even in those individuals who are officially diagnosed with osteoarthritis, many pro-inflammatory cytokines are released. This may not be due to the immune dis-regulation associated with rheumatoid arthritis, but instead can be caused by a myriad of other factors, such as toxicity and high levels of oxidative stress, which lead to accelerated tissue destruction [2].

Comparison the Effects of Cerium Nanoparticles (CeNP) and Cerium Oxide (CeO2) on Oxidative Toxic Stress in Human Lymphocytes

1 Student Research Committee, Hamadan University of Medical Sciences, Hamadan, ‎Iran.‎ 2 Department of Molecular Medicine and Genetic, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. 3 Department of Medical Nanotechnology, Faculty of Advanced Sciences & Technology, Pharmaceutical Sciences Branch, Islamic Azad University , Tehran, Iran. 4 Laboratory of Plant Cell Biology, Department of Biology, Bu-Ali Sina University, Hamedan, Iran.

Magnolia bark extract is a potent Nrf2 activator

Oxidative and xenobiotic stress have been shown to be causative agents for many diseases including cancer, age-related macular degeneration, cardiovascular diseases, and age-related memory loss. Cells have protection mechanisms against these stressors, in part, through the activation of the Nrf2 pathway. Research suggests that promoting health resilience could be achieved by transiently activating the Nrf2 pathway through an intake of dietary phytochemicals in the absence of oxidative stressors. Magnolia (Magnolia officinalis) bark has been widely used in traditional Chinese medicine they are rich in Magnolol and Honokiol. Here, we demonstrate that magnolia bark extract stimulates the Nrf2 pathway in mammalian liver cells both by reporter and gene expression assay. We also show that Magnolia bark helps protect cells against oxidative stress toxicity. We further carried out bioassay directed fractionation of the extract and show that the NRF2 activation is due to, in part, by the phytochemicals, magnolol and 4 methoxy honokiol, present in the magnolia bark extract.

Deciphering the underlying mechanisms of oxidation-state dependent cytotoxicity of graphene oxide on mammalian cells

The promising broad applications of graphene oxide (GO) derivatives in biomedicine have raised concerns about their safety on biological organisms. However, correlations between the physicochemical properties, especially oxidation degree of GOs and their toxicity, and the underlying mechanisms are not well understood. Herein, we evaluated the cytotoxicity of three GO samples with various oxidation degrees on mouse embryo fibroblasts (MEFs). Three samples can be internalized by MEFs observed via transmission electron microscopy (TEM), and were well tolerant by MEFs at lower doses (below 25μg/ml) but significantly toxic at 50 and 100μg/ml via Cytell Imaging System. More importantly, as the oxidation degree decreased, GO derivatives led to a higher degree of cytotoxicity and apoptosis. Meanwhile, three GOs stimulated dramatic enhancement in reactive oxygen species (ROS) production in MEFs, where the less oxidized GO produced a higher level of ROS, suggesting the major role of oxidative stress in the oxidation-degree dependent toxicity of GOs. Results from electron spin resonance (ESR) spectrometry showed a strong association of the lower oxidation degree of GOs with their stronger indirect oxidative damage through facilitating H2O2 decomposition into OH and higher direct oxidative abilities on cells. The theoretical simulation revealed the key contributions of carboxyl groups and aromatic domain size of nanosheets to varying the energy barrier of H2O2 decomposition reaction. These systematic explorations in the chemical mechanisms unravel the key physicochemical properties that would lead to the diverse toxic profiles of the GO nanosheets with different oxygenation levels, and offer us new clues in the molecular design of carbon nanomaterials for their safe applications in biomedicine.

Oral treatment with herbal formula B401 alleviates penile toxicity in aging mice with manganism.

The present study aims to elucidate the roles of nitric oxide synthase activity, oxidative stress, inflammation, and apoptosis in penile toxicity of aging mice associated with excess manganese (Mn) treatment and to investigate the effect of oral treatment with the herbal formula B401 in this respect. ICR strain mice were divided into two groups: the vehicle (sham group) and the B401 (50 mg/kg) group. The mice were orally treated for 5 days; then a high single dose of MnCl2 (100 mg/kg) was given by intraperitoneal injection to the mice. One day after MnCl2 treatment, corpora cavernosal tissues of both Mn-treated mice and their controls were simultaneously sampled to examine their immunohistochemical staining and Western blot analysis. Nitric oxide (NO) production, levels of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), expression levels of factors governing angiogenesis (vascular endothelial growth factor), oxidative stress (catalase, superoxide dismutase 2,4-hydroxynonenal), inflammation (tumor necrosis factor alpha), apoptosis (B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X protein [Bax], cleaved poly(adenosine diphosphate-ribose) polymerase [c-PARP], cytochrome C, caspase-12, and caspase-3) were evaluated in penile corpus cavernosum of the mice. We found that penile toxicity in the mice was enhanced under excess Mn treatment through reduction of NOS activity and increase in oxidative stress, inflammation, and apoptosis in the penile cavernous tissue. Furthermore, the penile toxicity in mice with manganism was alleviated by oral B401 treatment through enhancement of both nitric oxide synthesis and angiogenesis, with simultaneous reduction of oxidative stress, inflammation, and apoptosis in penile corpus cavernosum. We suggest that the herbal formula B401 may serve as a potential dietotherapeutic supplement for penile toxicity or dysfunction in aging males.

Oxidative stress and mitochondrial dysfunction in infected pregnant

The infected pregnant women have been various perinatal complications. The aim of the work was to clarify the role of oxidative stress and mitochondrial dysfunction in the development of perinatal complications in infected pregnant. Methods. The study included 68 pregnant women with signs of maternal-fetal infection (MFI) and 30 pregnant women who were found infected (control group). Later pregnant with MFI were divided into 2 groups: the first included 30 women who received traditional antibacterial and antiviral therapy, the second group consisted of 28 women who were additionally given an immunomodulator in combination with ozone therapy. Results. During pregnancy with MFI it is characterized the thrombophilic disorders, break immune homeostasis pregnant, endothelial dysfunction, which adversely affects perinatal indicators. Conclusions. The use of immunomodulators and ozone therapy in the complex treatment of MFI is pathogenetically substantiated effective treatment of oxidative stress and mitochondrial toxicity in the prevention of perinatal complications in infected women

WIN 55,212-2, agonist of cannabinoid receptors, prevents amyloid β1-42 effects on astrocytes in primary culture.

Alzheimer´s disease (AD), a neurodegenerative illness involving synaptic dysfunction with extracellular accumulation of Aβ1-42 toxic peptide, glial activation, inflammatory response and oxidative stress, can lead to neuronal death. Endogenous cannabinoid system is implicated in physiological and physiopathological events in central nervous system (CNS), and changes in this system are related to many human diseases, including AD. However, studies on the effects of cannabinoids on astrocytes functions are scarce. In primary cultured astrocytes we studied cellular viability using MTT assay. Inflammatory and oxidative stress mediators were determined by ELISA and Western-blot techniques both in the presence and absence of Aβ1-42 peptide. Effects of WIN 55,212-2 (a synthetic cannabinoid) on cell viability, inflammatory mediators and oxidative stress were also determined. Aβ1-42 diminished astrocytes viability, increased TNF-α and IL-1β levels and p-65, COX-2 and iNOS protein expression while decreased PPAR-γ and antioxidant enzyme Cu/Zn SOD. WIN 55,212-2 pretreatment prevents all effects elicited by Aβ1-42. Furthermore, cannabinoid WIN 55,212-2 also increased cell viability and PPAR-γ expression in control astrocytes. In conclusion cannabinoid WIN 55,212-2 increases cell viability and anti-inflammatory response in cultured astrocytes. Moreover, WIN 55,212-2 increases expression of anti-oxidant Cu/Zn SOD and is able to prevent inflammation induced by Aβ1-42 in cultured astrocytes. Further studies would be needed to assess the possible beneficial effects of cannabinoids in Alzheimer's disease patients.

P1132 : Regulation of oxidative stress and lipid peroxidation in methotrexate-induced liver toxicity by pretreatment with turmeric

P1132 : Regulation of oxidative stress and lipid peroxidation in methotrexate-induced liver toxicity by pretreatment with turmeric

Cell line-specific oxidative stress in cellular toxicity: A toxicogenomics-based comparison between liver and colon cell models

Imbalance between high reactive oxygen species formation and antioxidant capacity in the colon and liver has been linked to increased cancer risk. However, knowledge about possible cell line-specific oxidative stress-mechanisms is limited. To explore this further, gene expression data from a human liver and colon cell line (HepG2/Caco-2), both exposed to menadione and H2O2 at six time points (0.5–1–2–4–8 and 24h) were compared in association with cell cycle distribution. In total, 3164 unique- and 1827 common genes were identified between HepG2 and Caco-2 cells. Despite the higher number of unique genes, most oxidative stress-related genes such as CAT, OGG1, NRF2, NF-κB, GCLC, HMOX1 and GSR were differentially expressed in both cell lines. However, cell-specific regulation of genes such as KEAP1 and GCLM, or of the EMT pathway, which are of pathophysiological importance, indicates that oxidative stress induces different transcriptional effects and outcomes in the two selected cell lines. In addition, expression levels and/or -direction of common genes were often different in HepG2 and Caco-2 cells, and this led to very diverse downstream effects as confirmed by correlating pathways to cell cycle changes. Altogether, this work contributes to obtaining a better molecular understanding of cell line-specific toxicity upon exposure to oxidative stress-inducing compounds.

Protective effect of antioxidants on DNA damage in leukocytes from X-linked adrenoleukodystrophy patients

Toxic metabolites accumulation and oxidative stress have been associated to the pathophysiology of X-linked adrenoleukodystrophy (X-ALD), an inborn error of peroxisome metabolism. Parameters of oxidative damage to proteins and lipids in X-ALD patients were already described in literature; however, DNA injuries were not studied yet. Considering that, the aims were to investigate DNA damage by comet assay in heterozygotes and symptomatic X-ALD patients, to look for associations between DNA damage and lipid peroxidation as measured by urinary 15-F2t-isoprostane; and to evaluate the in vitro effect of N-acetyl-l-cysteine (NAC), trolox (TRO) and rosuvastatin (RSV) on DNA damage in leukocytes from symptomatic patients. Symptomatic patients presented higher DNA damage levels than those found in heterozygotes and controls; heterozygotes and controls showed similar results. In order to investigate the in vitro antioxidant effect on DNA damage, whole blood cells from symptomatic patients were incubated with NAC (1 and 2.5mM), TRO (25 and 75μM) and RSV (0.5, 2 and 5μM) before DNA damage analysis. NAC, TRO and RSV, at all tested concentrations, were all capable to reduce DNA damage in symptomatic X-ALD patients until control levels. Finally, DNA damage correlated with urinary isoprostanes and plasmatic levels of TBA-RS and DCFH-DA, allowing to hypothesize that DNA damage might be induced by lipid peroxidation in symptomatic patients. The present work yields experimental evidence that NAC, TRO and RSV reduce the in vitro DNA injury in symptomatic X-ALD patients, what may suggest that the administration of these antioxidants might be considered as an adjuvant therapy for X-ALD.

Occupational exposure to chemicals and oxidative toxic stress

Humans are occupationally and environmentally exposed to different types of xenobiotics such as pesticides and metals. Exposure to these compounds can alter the oxidants/prooxidants and antioxidants balance through increasing oxidative toxic stress (OTS) condition. OTS can be defined as the exposure of molecule, cell or tissue, to the excess levels of oxidants, particularly to the free radicals, such as superoxide or hydroxyl radicals, which commonly refer to reactive oxygen species (ROS). OTS may occur either due to the overproduction of ROS or to the decrease of cellular antioxidant levels. There is now a strong body of evidence indicating that exposure to chemicals in workplaces is mediated via oxidant signaling pathways. The aim of this review is to provide an overview of the role of some common chemicals in formation of free radicals and the induction of OTS.

Trihalomethanes in liver pathology: Mitochondrial dysfunction and oxidative stress in the mouse.

Trihalomethanes (THMs) are disinfection byproducts found in chlorinated water, and are associated with several different kinds of cancer in human populations and experimental animal models. Metabolism of THMs proceeds through enzymes such as GSTT1 and CYP2E1 and gives rise to reactive intermediates, which form the basis for their toxic activities. The aim of this study was to assess the mitochondrial dysfunction caused by THMs at low levels, and the resulting hepatic histological and biochemical changes in the mouse. Male ICR mice were administered with two THMs: dibromochloromethane (DBCM) and bromodichloromethane (BDCM); once daily, by gavage, to a total of four administrations. Animals were sacrificed four weeks after DBCM and BDCM administrations. Blood biochemistry was performed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), albumin (Alb), total protein (TP), creatinine, and urea. Animals exposed to DBCM and BDCM showed elevated ALT and TB levels (p < 0.05) as compared with controls. Histological analysis confirmed the presence of vacuolar degenerescence and a multifocal necrotizing hepatitis in 33% of animals (n = 2). Mitochondrial analysis showed that THMs reduced mitochondrial bioenergetic activity (succinate dehydrogenase (SQR), cytochrome c oxidase (COX), and ATP synthase) and increased oxidative stress (glutathione S-transferase (GST)) in hepatic tissues (p < 0.05). These results add detail to the current understanding of the mechanisms underlying THM-induced toxicity, supporting the role of mitochondrial dysfunction and oxidative stress in liver toxicity caused by DBCM and BDCM. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1009-1016, 2016.

Characterization of Water Melon (&amp;lt;i&amp;gt;Citrullus lanatus&amp;lt;/i&amp;gt;) Genotypes under High Salinity Regime

For horticultural crops and especially for vegetables, salinity is dilemma. It is the most limiting factor for plant growth and development by producing reactive oxygen species and ultimately oxidative stress. In the present study, the screening of watermelon (Citrullus lanatus Thanb. Mavs.) Cultivars was observed for salt tolerance. Four salinity levels (1.5, 3, 4.5, and 6 dS·m-1 NaCl) and six cultivars (Crimson, Charleston Gray, Anarkali, Chairman, Sugar Baby and Champion) tested for screening. It was observed that all morphological attributes and ionic contents were severely affected. But it was revealed by statistical analysis that Charleston Gray was affected least while Champion was most salt sensitive cultivar due to oxidative stress and ionic toxicity. It is concluded that different genotypes under consideration vary in their ability to tolerate salt stress.

Pretreatment with diallylsulphide modulates mercury-induced neurotoxicity in male rats.

Many studies have reported on the toxicity and related oxidative stress of mercury. Antioxidants play an important role in counteracting metal-induced neurotoxicity under in vivo conditions. In this study, the effect of diallylsulphide (DAS) was evaluated on mercuric chloride induced activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione content in brains of rats. Pretreatment of rats with DAS in the Hg-treated group also inhibited an increase in lipid peroxidation and elevated acetyl cholinesterase and glutathione content. Activities of antioxidant enzymes were also restored concomitantly when compared to the control rats after DAS administration. DAS also caused a decrease in tumor necrosis factor-α level which was higher in HgCl2-treated group. The results indicate that DAS augments antioxidant defense with anti-inflammatory response against HgCl2-induced neurotoxicity. The increased level of antioxidant enzymes enhances the antioxidant potential of the organ to reduce oxidative stress.

Defective copper transport in the copt5 mutant affects cadmium tolerance.

Cadmium toxicity interferes with essential metal homeostasis, which is a problem for both plant nutrition and the consumption of healthy food by humans. Copper uptake is performed by the members of the Arabidopsis high affinity copper transporter (COPT) family. One of the members, COPT5, is involved in copper recycling from the vacuole toward the cytosolic compartment. We show herein that copt5 mutants are more sensitive to cadmium stress than wild-type plants, as indicated by reduced growth. Exacerbated cadmium toxicity in copt5 mutants is due specifically to altered copper traffic through the COPT5 transporter. Three different processes which have been shown to affect cadmium tolerance are altered in copt5 mutants. First, ethylene biosynthesis diminishes under copper deficiency and, in the presence of cadmium, ethylene production diminishes further. Copper deficiency responses are also attenuated under cadmium treatment. Remarkably, while copt5 roots present higher oxidative stress toxicity symptoms than controls, aerial copt5 parts display lower oxidative stress, as seen by reduced cadmium delivery to shoots. Taken together, these results demonstrate that copper transport plays a key role in cadmium resistance, and suggest that oxidative stress triggers an NADPH oxidase-mediated signaling pathway, which contributes to cadmium translocation and basal plant resistance. The slightly lower cadmium levels that reach aerial parts in the copt5 mutants, irrespective of the copper content in the media, suggest a new biotechnological approach to minimize toxic cadmium entry into food chains.