scholarly journals Mitochondrial, lysosomal and DNA damages induced by acrylamide attenuate by ellagic acid in human lymphocyte

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247776
Author(s):  
Ahmad Salimi ◽  
Elahe Baghal ◽  
Hassan Ghobadi ◽  
Niloufar Hashemidanesh ◽  
Farzad Khodaparast ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Dna Damage ◽  
Ellagic Acid ◽  
Human Lymphocytes ◽  
Health Concern ◽  
Cytochrome P450 Enzyme ◽  
Dna Damages ◽  
Ros Formation

Acrylamide (AA), is an important contaminant formed during food processing under high temperature. Due to its potential neurotoxicity, reproductive toxicity, hepatotoxicity, immunotoxicity, genotoxicity and carcinogenicity effects, this food contaminant has been recognized as a human health concern. Previous studies showed that acrylamide-induced toxicity is associated with active metabolite of acrylamide by cytochrome P450 enzyme, oxidative stress, mitochondrial dysfunction and DNA damage. In the current study, we investigated the role of oxidative stress in acrylamide’s genotoxicity and therapeutic potential role of ellagic acid (EA) in human lymphocytes. Human lymphocytes were simultaneously treated with different concentrations of EA (10, 25 and 50 μM) and acrylamide (50 μM) for 4 h at 37°C. After 4 hours of incubation, the toxicity parameters such cytotoxicity, ROS formation, oxidized/reduced glutathione (GSH/GSSG) content, malondialdehyde (MDA) level, lysosomal membrane integrity, mitochondria membrane potential (ΔΨm) collapse and 8-hydroxy-2’-deoxyguanosine (8-OHdG) were analyzed using biochemical and flow cytometry evaluations. It has been found that acrylamide (50 μM) significantly increased cytotoxicity, ROS formation, GSH oxidation, lipid peroxidation, MMP collapse, lysosomal and DNA damage in human lymphocytes. On the other hand, cotreatment with EA (25 and 50 μM) inhibited AA-induced oxidative stress which subsequently led to decreasing of the cytotoxicity, GSH oxidation, lipid peroxidation, MMP collapse, lysosomal and DNA damage. Together, these results suggest that probably the co-exposure of EA with foods containing acrylamide could decrease mitochondrial, lysosomal and DNA damages, and oxidative stress induced by acrylamide in human body.

Curcumin protects DNA damage in a chronically arsenic-exposed population of West Bengal

2010 ◽  
Vol 29 (6) ◽  
pp. 513-524 ◽  
Author(s):  
Jaydip Biswas ◽  
Dona Sinha ◽  
Sutapa Mukherjee ◽  
Soumi Roy ◽  
Maqsood Siddiqi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Dna Damage ◽  
West Bengal ◽  
Health Hazard ◽  
Human Lymphocytes ◽  
Protein Carbonyl ◽  
Ros Generation ◽  
Exposed Population

Groundwater arsenic contamination has been a health hazard for West Bengal, India. Oxidative stress to DNA is recognized as an underlying mechanism of arsenic carcinogenicity. A phytochemical, curcumin, from turmeric appears to be potent antioxidant and antimutagenic agent. DNA damage prevention with curcumin could be an effective strategy to combat arsenic toxicity. This field trial in Chakdah block of West Bengal evaluated the role of curcumin against the genotoxic effects of arsenic. DNA damage in human lymphocytes was assessed by comet assay and fluorescence-activated DNA unwinding assay. Curcumin was analyzed in blood by high performance liquid chromatography (HPLC). Arsenic induced oxidative stress and elucidation of the antagonistic role of curcumin was done by observation on reactive oxygen species (ROS) generation, lipid peroxidation and protein carbonyl. Antioxidant enzymes like catalase, superoxide dismutase, glutathione reductase, glutathioneS-transferase, glutathione peroxidase and non-enzymatic glutathione were also analyzed. The blood samples of the endemic regions showed severe DNA damage with increased levels of ROS and lipid peroxidation. The antioxidants were found with depleted activity. Three months curcumin intervention reduced the DNA damage, retarded ROS generation and lipid peroxidation and raised the level of antioxidant activity. Thus curcumin may have some protective role against the DNA damage caused by arsenic.

Chronic Lymphocytic Leukemia: Correlations Between Oxidative Stress Metabolism and Cytogenetic Subgroups

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4157-4157
Author(s):  
Felix Carbonell ◽  
Isabel Oliver ◽  
Rosa Collado ◽  
Carmen Tormos ◽  
Antonio Iradi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Dna Damage ◽  
Chronic Lymphocytic Leukemia ◽  
Chromosomal Abnormalities ◽  
Lymphocytic Leukemia ◽  
Oxidative Stress Marker ◽  
Antioxidant Enzyme Activities ◽  
Oxygen Intermediates

Abstract The chronic lymphocytic leukemia (B cell-CLL) is a heterogeneous lymphoproliferative disorder susceptible to oxidative stress. The excessive production of reactive oxygen intermediates above the capability of naturally produced antioxidants may result in the instability of essential macromolecules, and represents the molecular basis of many diseases including cancer. Highly reactive radicals interact with DNA inducing a multitude of oxidative modifications, and are implicated in mutagenesis due to misreplication of the damaged base 8-oxo-2′-deoxiguanosine (8-oxo-dG). Furthermore, protooncogene activation and/or tumor suppressor gene inhibition has been reported as a consequence of oxygen radical-induced DNA modification. Even though their molecular alterations involving different genes as TP53 (17p13.1) and ATM (11q22-23) in B-cells CLL has been well established, the role of oxidative stress is still poorly understood and a matter of our interest. The aim of the present study was to analyze the correlations between oxidative stress status and the most common genetic subgroups in B-CLL. Patients and methods: We analyzed peripheral blood and urine from 86 untreated patients with B-CLL, and 39 normal controls. DNA damage was measured assessing the levels of 8-oxo-dG by HPLC-EC. Lipid peroxidation was studied quantifying the levels of malondialdehyde (MDA) and 8-isoprostane by HPLC-EC and enzyme immunoassay, respectively. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were examined by spectrophotometric methods; and the oxidative stress marker oxidized/reduced glutathione ratio (GSSG/GSH) was measured by HPLC. Genetic abnormalities were analyzed by fluorescence in situ hybridization (FISH) technique with LSI D13S19, LSI ATM, LSI P53 and CEP 12 probes (Abbott Molecular Inc, Des Plaines, IL, USA). Results: With regard to antioxidant enzyme activities, there was a significantly decrease of SOD (range: 1.53–13.19 vs 11.88±3.25, p<0.001) and CAT (15.27–68.42 vs 47.15±16.45, p<0.05) levels in all B-CLL cytogenetic subgroups as compared with control subjects. On the contrary, GPx activity increased significantly among patients with del(13q) (31.22±16.53 vs 13.60±5.72, p<0.05). There was also a general increase of GSH (0.64–13.69 vs 0.45±0.51, p<0.001) and GSSG (14.41–67.47 vs 21.12±3.50, p<0.001) content in lymphocytes of CLL patients. As a consequence, the GSSG/GSH x 100 ratio (1.34–43.78 vs 1.95±1.94, p<0.001) increased indicating that the thiol redox status is elevated in CLL lymphocytes. In addition, there was an extensive lipid peroxidation as indicated by the increase of MDA and 8-isoprostane, especially among cases with ATM (MDA/8-isoprostane: 1.98±1.61/118.87±25.96 vs 0.21±0.10/74.64±33.94, p<0.001 and p<0.05) and TP53 (MDA: 2.09±0.78 vs 0.21±0.10, p<0.001) deletions. Finally, DNA damage was also enhanced in B-CLL. The mutagenic base 8-oxo-dG was found to be significantly increased in the lymphocytes DNA and urine of CLL patients (CLL lymphocytes: 13.20–92.64 vs 12.99±18.30, p<0.001 and urine 1.19–85.05 vs 7.43±2.63, p<0.001). Conclusion: Several oxidative stress parameters could relate to the prognostic role of some chromosomal abnormalities, as the favorable increase of GPx in patients with del(13q), the low oxidative damage among cases of trisomy 12, or the DNA and lipid deterioration of patients with ATM and TP53 deletions.

Toxicity of carbon tetrachloride, free radicals and role of antioxidants

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Velid Unsal ◽  
Mustafa Cicek ◽  
İlhan Sabancilar
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Endoplasmic Reticulum ◽  
Free Radicals ◽  
Carbon Tetrachloride ◽  
Side Effects ◽  
Oxidative Damage ◽  
Cytochrome P450 Enzyme ◽  
Pathological Conditions

AbstractSeveral chemicals, including environmental toxicants and clinically useful drugs, cause severe cellular damage to different organs of our body through metabolic activation to highly reactive substances such as free radicals. Carbon tetrachloride is an organic compound of which chemical formula is CCl₄. CCl4 is strong toxic in the kidney, testicle, brain, heart, lung, other tissues, and particularly in the liver. CCl4 is a powerful hepatoxic, nephrotoxic and prooxidant agent which is widely used to induce hepatotoxicity in experimental animals and to create hepatocellular carcinoma, hepatic fibrosis/cirrhosis and liver injury, chemical hepatitis model, renal failure model, and nephrotoxicity model in recent years. The damage-causing mechanism of CCl4 in tissues can be explained as oxidative damage caused by lipid peroxidation which starts after the conversion of CCl4 to free radicals of highly toxic trichloromethyl radicals (•CCl₃) and trichloromethyl peroxyl radical (•CCl₃O2) via cytochrome P450 enzyme. Complete disruption of lipids (i.e., peroxidation) is the hallmark of oxidative damage. Free radicals are structures that contain one or more unpaired electrons in atomic or molecular orbitals. These toxic free radicals induce a chain reaction and lipid peroxidation in membrane-like structures rich in phospholipids, such as mitochondria and endoplasmic reticulum. CCl4-induced lipid peroxidation is the cause of oxidative stress, mitochondrial stress, endoplasmic reticulum stress. Free radicals trigger many biological processes, such as apoptosis, necrosis, ferroptosis and autophagy. Recent researches state that the way to reduce or eliminate these CCl4-induced negative effects is the antioxidants originated from natural sources. For normal physiological function, there must be a balance between free radicals and antioxidants. If this balance is in favor of free radicals, various pathological conditions occur. Free radicals play a role in various pathological conditions including Pulmonary disease, ischemia / reperfusion rheumatological diseases, autoimmune disorders, cardiovascular diseases, cancer, kidney diseases, hypertension, eye diseases, neurological disorders, diabetes and aging. Free radicals are antagonized by antioxidants and quenched. Antioxidants do not only remove free radicals, but they also have anti-inflammatory, anti-allergic, antithrombotic, antiviral, and anti-carcinogenic activities. Antioxidants contain high phenol compounds and antioxidants have relatively low side effects compared to synthetic drugs. The antioxidants investigated in CCI4 toxicity are usually antioxidants from plants and are promising because of their rich resources and low side effects. Data were investigated using PubMed, EBSCO, Embase, Web of Science, DOAJ, Scopus and Google Scholar, Carbon tetrachloride, carbon tetrachloride-induced toxicity, oxidative stress, and free radical keywords. This study aims to enlighten the damage-causing mechanism created by free radicals which are produced by CCl4 on tissues/cells and to discuss the role of antioxidants in the prevention of tissue/cell damage. In the future, Antioxidants can be used as a therapeutic strategy to strengthen effective treatment against substances with high toxicity such as CCl4 and increase the antioxidant capacity of cells.

Mitochondrial and lysosomal protective agents ameliorate cytotoxicity and oxidative stress induced by cyclophosphamide and methotrexate in human blood lymphocytes

2019 ◽  
Vol 38 (11) ◽  
pp. 1266-1274 ◽  
Author(s):  
A Salimi ◽  
R Pirhadi ◽  
Z Jamali ◽  
M Ramazani ◽  
BS Yousefsani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Mitochondrial Membrane ◽  
Human Lymphocytes ◽  
Membrane Damage ◽  
Lysosomal Membrane ◽  
Protective Agents ◽  
Blood Lymphocytes ◽  
Ros Formation ◽  
And Oxidative Stress

Cyclophosphamide (CYP) and methotrexate (MTX) have been evaluated for their ability to induce toxicity in human peripheral blood lymphocytes (PBLs) and the protective role of mitochondrial and lysosomal stabilizing agents. The potential toxicity effects of CYP and MTX were measured in vitro by cellular parameters assays such as cellular viability, reactive oxygen species (ROS) formation, mitochondrial membrane permeability transition (mitochondrial membrane potential (MMP)) collapse, lysosomal membrane damage, intracellular reduced glutathione (GSH), extracellular oxidized glutathione (GSSG), and lipid peroxidation. Separately, human lymphocytes were treated with concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 ng/mL for CYP and 1, 2, 5, and 10 µg/mL for MTX for 6 h. Statistical evaluations showed that CYP and MTX significantly decreased the cell viability at the three highest concentrations when compared with both the negative and solvent controls. In addition, CYP and MTX were significantly induced ROS formation, MMP collapse, lysosomal membrane damage, lipid peroxidation, and GSH depletion compared with the controls. Mitochondrial and lysosomal protective agents like cyclosporine A and chloroquine, respectively, decreased cytotoxicity and oxidative stress induced by CYP and MTX. The present results indicate that CYP and MTX are toxic to human PBLs and their toxicity could be ameliorated by mitochondrial and lysosomal protective agents.

scholarly journals Insights in the Role of Lipids, Oxidative Stress and Inflammation in Rheumatoid Arthritis Unveiled by New Trends in Lipidomic Investigations

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 45
Author(s):  
Helena Beatriz Ferreira ◽  
Tânia Melo ◽  
Artur Paiva ◽  
Maria do Rosário Domingues
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Lipid Profile ◽  
Inflammatory Responses ◽  
Molecular Level ◽  
Lipid Hydroperoxides ◽  
Lipid Species ◽  
Inflammatory Autoimmune Disease

Rheumatoid arthritis (RA) is a highly debilitating chronic inflammatory autoimmune disease most prevalent in women. The true etiology of this disease is complex, multifactorial, and is yet to be completely elucidated. However, oxidative stress and lipid peroxidation are associated with the development and pathogenesis of RA. In this case, oxidative damage biomarkers have been found to be significantly higher in RA patients, associated with the oxidation of biomolecules and the stimulation of inflammatory responses. Lipid peroxidation is one of the major consequences of oxidative stress, with the formation of deleterious lipid hydroperoxides and electrophilic reactive lipid species. Additionally, changes in the lipoprotein profile seem to be common in RA, contributing to cardiovascular diseases and a chronic inflammatory environment. Nevertheless, changes in the lipid profile at a molecular level in RA are still poorly understood. Therefore, the goal of this review was to gather all the information regarding lipid alterations in RA analyzed by mass spectrometry. Studies on the variation of lipid profile in RA using lipidomics showed that fatty acid and phospholipid metabolisms, especially in phosphatidylcholine and phosphatidylethanolamine, are affected in this disease. These promising results could lead to the discovery of new diagnostic lipid biomarkers for early diagnosis of RA and targets for personalized medicine.

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