Apocynin attenuates patulin-induced cytotoxicity through reduction of oxidation stress and apoptosis in HEK293cells

2020 ◽  
pp. 1-10
Author(s):  
J.H. Han ◽  
Y.J. Zhong ◽  
C.N. Jin ◽  
R.L. Luo ◽  
M.Y. Xia ◽  
...  
Keyword(s):  
Cell Injury ◽  
Reduced Glutathione ◽  
Hek293 Cells ◽  
Oxygen Species ◽  
Human Embryonic Kidney ◽  
Oxidation Stress ◽  
Mitochondria Membrane Potential ◽  
Alternative Intervention ◽  
Lactate Dehydrogenase Release ◽  
Derivative Products

Patulin (PAT) is a natural mycotoxin that commonly contaminates fruits and their derivative products and has been proven to induce cytotoxicity and oxidative damage in renal cells. In the present study, we aimed to evaluate the effect of apocynin, a potent phenolic antioxidant isolated from plants, on PAT-induced cell injury in human embryonic kidney (HEK293) cells. Compared with 7.5 μM PAT treatment alone, 10 μM apocynin co-treatment elevated cell viability, alleviated lactate dehydrogenase release and reduced caspase activities. Furthermore, apocynin inhibited reactive oxygen species overproduction, re-established mitochondria membrane potential and elevated intracellular ATP content. In addition, the results showed that apocynin aggrandized reduced glutathione (GSH) content, reduced oxidized glutathione (GSSG) content, raised the GSH/GSSG ratio and elevated superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase activities. Collectively, results of the study clearly show that apocynin supplement may serve as an alternative intervention to protect HEK293 cells against cytotoxicity induced by PAT through reduction of oxidation stress and apoptosis.

scholarly journals Transcriptomic and Proteomic Analysis Reveals Mechanisms of Patulin-Induced Cell Toxicity in Human Embryonic Kidney Cells

Toxins ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 681
Author(s):  
Nianfa Han ◽  
Ruilin Luo ◽  
Jiayu Liu ◽  
Tianmin Guo ◽  
Jiayu Feng ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Digital Gene Expression ◽  
Hek293 Cells ◽  
Kidney Cells ◽  
Oxygen Species ◽  
Human Embryonic Kidney ◽  
Absolute Quantitation ◽  
Human Embryonic Kidney Cells ◽  
Isobaric Tags ◽  
Induced Apoptosis

Patulin (PAT) is a natural mycotoxin that commonly contaminates fruits and fruit-based products. Previous work indicated that PAT-induced apoptosis in which reactive oxygen species (ROS) are involved in human embryonic kidney (HEK293) cells. To uncover novel aspects of the possible mechanism of PAT nephrotoxicity, the transcriptome and proteome profiles were investigated using the digital gene expression (DGE) and isobaric tags for relative and absolute quantitation (iTRAQ) proteomic approaches. A total of 127 genes and 85 proteins were found to express differentially in response to 5 μM PAT for 10 h in HEK293 cells. The most dramatic changes of expression were noticed with genes or proteins related to apoptosis, oxidative phosphorylation ribosome and cell cycle. Especially, the activation of caspase 3, UQCR11, active transport form and endocytosis appeared to be crucial in PAT kidney cytotoxicity. PAT also seemed to be associated with cancer and neuropathic disease as pathways associated with carcinogenesis, Alzheimer’s disease and Parkinson’s disease were induced. Overall, this study served to uncover overall insights associated with signaling pathway that modulated the PAT toxicity mechanism.

Bergenin Exhibits Hepatoprotective Activity Against Ethanol-Induced Oxidative Stress in ICR Mice

2019 ◽  
Vol 18 (4) ◽  
pp. 297-302
Author(s):  
Sriset Yollada ◽  
Chatuphonprasert Waranya ◽  
Jarukamjorn Kanokwan
Keyword(s):  
Reactive Oxygen Species ◽  
Gallic Acid ◽  
Aspartate Aminotransferase ◽  
Alanine Aminotransferase ◽  
Hepatic Injury ◽  
Reduced Glutathione ◽  
Reactive Oxygen ◽  
Hepatoprotective Activity ◽  
Oxygen Species ◽  
Hepatic Glutathione

Bergenin is a C-glucoside derivative of gallic acid but its antioxidant and hepatoprotective effects have not previously been compared with gallic acid. Male ICR mice were administered bergenin (10, 50, and 250 mg/kg/day) or gallic acid (100 mg/kg/day) for 7 consecutive days before a single administration of ethanol (5 g/kg). Liver sections were histopathologically examined. Aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde levels were determined in plasma. Total glutathione, reduced glutathione, and oxidized glutathione levels were determined in liver homogenates. Ethanol induced hepatic injury with prominent histopathological markers including nuclear pyknosis and necrotic areas and this accorded with increases in the plasma levels of aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde. Moreover, ethanol disturbed hepatic glutathione homeostasis by reducing glutathione stores. Hepatic injury in the ethanol-induced mice was prevented with bergenin and gallic acid by significant decreases in plasma aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde levels and restoration of the hepatic glutathione profile through an increase in the reduced glutathione/oxidized glutathione ratio. Bergenin at 10 mg/kg/day showed comparable hepatoprotective activity to gallic acid in an ethanol-induced mouse model of oxidative stress. Therefore, bergenin might be a promising candidate for further development as a novel hepatoprotective product.

Renal Cortical Slices: An In Vitro Model for Kidney Metabolism and Toxicity

1992 ◽  
Vol 20 (1) ◽  
pp. 71-76
Author(s):  
Andrea Trevisan ◽  
Stefano Maso ◽  
Paola Meneghetti
Keyword(s):  
Wistar Rats ◽  
Reduced Glutathione ◽  
Organic Anion ◽  
Cortical Slice ◽  
Lactate Dehydrogenase Release ◽  
Age Related ◽  
Renal Cortical Slice ◽  
Male Wistar Rats ◽  
Vitro Model

The in vitro renal cortical slice model was used to study: 1) the effects on the kidney of some haloalkanes and haloalkenes using 3-month-old male Wistar rats; 2) influence of age and sex on renal cortical slice indices in non-treated rats; and 3) effects of 1,2-dichloropropane on the slices after pretreatment of 3-month-old male Wistar rats with DL-butathionine-[S,R]-sulphoximine. The most nephrotoxic chemical used was 1,3-dichloropropene, which caused a total depletion in the levels of reduced glutathione, a high peroxidation of lipid (about three thousand-fold with respect to control), a significant release of tubular enzymes into the medium, and loss of organic anion ( p-aminohippurate) accumulation. All the chemicals affected the cytosol more than the brush border. The most remarkable age-related differences in the untreated slices were the progressive decrease of reduced glutathione (p<0.05 from three months of age), and an increase in lactate dehydrogenase release into the medium (p<0.05 from six months of age). By contrast, sex differences were slight. The ‘treatment with 1,2-dichloropropane of slices prepared from rats pretreated with DL-butathionine-[S,R]-sulphoximine significantly increased the depletion of glutathione content (p<0.05) and malondialdehyde release in the medium (p<0.001) caused by the solvent alone.

scholarly journals TRPM2 Non-Selective Cation Channels in Liver Injury Mediated by Reactive Oxygen Species

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1243
Author(s):  
Eunus S. Ali ◽  
Grigori Y. Rychkov ◽  
Greg J. Barritt
Keyword(s):  
Reactive Oxygen Species ◽  
Liver Injury ◽  
Cell Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Cell Types ◽  
Chronic Liver ◽  
Oxygen Species ◽  
Alcoholic Fatty Liver ◽  
Trpm2 Channels

TRPM2 channels admit Ca2+ and Na+ across the plasma membrane and release Ca2+ and Zn2+ from lysosomes. Channel activation is initiated by reactive oxygen species (ROS), leading to a subsequent increase in ADP-ribose and the binding of ADP-ribose to an allosteric site in the cytosolic NUDT9 homology domain. In many animal cell types, Ca2+ entry via TRPM2 channels mediates ROS-initiated cell injury and death. The aim of this review is to summarise the current knowledge of the roles of TRPM2 and Ca2+ in the initiation and progression of chronic liver diseases and acute liver injury. Studies to date provide evidence that TRPM2-mediated Ca2+ entry contributes to drug-induced liver toxicity, ischemia–reperfusion injury, and the progression of non-alcoholic fatty liver disease to cirrhosis, fibrosis, and hepatocellular carcinoma. Of particular current interest are the steps involved in the activation of TRPM2 in hepatocytes following an increase in ROS, the downstream pathways activated by the resultant increase in intracellular Ca2+, and the chronology of these events. An apparent contradiction exists between these roles of TRPM2 and the role identified for ROS-activated TRPM2 in heart muscle and in some other cell types in promoting Ca2+-activated mitochondrial ATP synthesis and cell survival. Inhibition of TRPM2 by curcumin and other “natural” compounds offers an attractive strategy for inhibiting ROS-induced liver cell injury. In conclusion, while it has been established that ROS-initiated activation of TRPM2 contributes to both acute and chronic liver injury, considerable further research is needed to elucidate the mechanisms involved, and the conditions under which pharmacological inhibition of TRPM2 can be an effective clinical strategy to reduce ROS-initiated liver injury.

Differential susceptibility of a few members of the nasuta–albomicans complex of Drosophila to paraquat-induced lethality and oxidative stress

Genome ◽  
2011 ◽  
Vol 54 (10) ◽  
pp. 829-835 ◽  
Author(s):  
Mysore S. Ranjini ◽  
Ravikumar Hosamani ◽  
Muralidhara ◽  
Nallur B. Ramachandra
Keyword(s):  
Oxidative Stress ◽  
Biochemical Analysis ◽  
Reduced Glutathione ◽  
Differential Susceptibility ◽  
Activity Levels ◽  
Oxygen Species ◽  
Stress Markers ◽  
The Status ◽  
Markers Of Oxidative Stress ◽  
And Oxidative Stress

The evolution of karyotypically stabilized short-lived (SL) and long-lived (LL) cytoraces in the laboratory have been established and validated through our previous lifespan studies. In the present investigation, we examined the possible reason(s) for the differential longevity among selected members of SL and LL cytoraces, employing the well known paraquat (PQ) resistance bioassay. Exposure of these races to varying concentrations of PQ revealed relatively higher resistance among LL cytoraces than SL cytoraces, as evident by the lower incidence of mortality. Biochemical analysis for endogenous markers of oxidative stress revealed that LL-2 cytorace exhibited lower reactive oxygen species (ROS) and lipid peroxidation (LPO) levels, higher activity levels of superoxide dismutase (SOD), and coupled with higher levels of reduced glutathione (GSH) compared with the levels found in SL-2 cytorace. These findings suggest that the higher susceptibility of SL cytoraces to PQ challenge may be, at least in part, related to the higher endogenous levels of oxidative stress markers. Although the precise mechanisms responsible for the longer longevity among LL cytoraces of the nasuta–albomicans complex of Drosophila merits further investigation, our data suggest that the relatively longer lifespan may be related to the status of endogenous markers that renders them more resistant towards oxidative-stress-mediated lethality, as evident in the PQ assay.

scholarly journals CYP450 Mediates Reactive Oxygen Species Production in a Mouse Model of β-Thalassemia through an Increase in 20-HETE Activity

2021 ◽  
Vol 22 (3) ◽  
pp. 1106
Author(s):  
Rayan Bou-Fakhredin ◽  
Batoul Dia ◽  
Hilda E. Ghadieh ◽  
Stefano Rivella ◽  
Maria Domenica Cappellini ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mouse Model ◽  
Cell Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Species Production ◽  
Different Sources ◽  
Dependent Pathway

Oxidative damage by reactive oxygen species (ROS) is one of the main contributors to cell injury and tissue damage in thalassemia patients. Recent studies suggest that ROS generation in non-transfusion-dependent (NTDT) patients occurs as a result of iron overload. Among the different sources of ROS, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes and cytochrome P450 (CYP450) have been proposed to be major contributors for oxidative stress in several diseases. However, the sources of ROS in patients with NTDT remain poorly understood. In this study, Hbbth3/+ mice, a mouse model for β-thalassemia, were used. These mice exhibit an unchanged or decreased expression of the major NOX isoforms, NOX1, NOX2 and NOX4, when compared to their C57BL/6 control littermates. However, a significant increase in the protein synthesis of CYP4A and CYP4F was observed in the Hbbth3/+ mice when compared to the C57BL/6 control mice. These changes were paralleled by an increased production of 20-hydroxyeicosatetraenoic acid (20-HETE), a CYP4A and CYP4F metabolite. Furthermore, these changes corroborate with onset of ROS production concomitant with liver injury. To our knowledge, this is the first report indicating that CYP450 4A and 4F-induced 20-HETE production mediates reactive oxygen species overgeneration in Hbbth3/+ mice through an NADPH-dependent pathway.

scholarly journals Glutathione Participation in the Prevention of Cardiovascular Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1220
Author(s):  
Deyamira Matuz-Mares ◽  
Héctor Riveros-Rosas ◽  
María Magdalena Vilchis-Landeros ◽  
Héctor Vázquez-Meza
Keyword(s):  
Cardiovascular Diseases ◽  
Superoxide Anion ◽  
Reactive Nitrogen Species ◽  
Hypochlorous Acid ◽  
Reduced Glutathione ◽  
Heart Diseases ◽  
Reactive Species ◽  
Oxygen Species ◽  
Cardiovascular Pathologies

Cardiovascular diseases (CVD) (such as occlusion of the coronary arteries, hypertensive heart diseases and strokes) are diseases that generate thousands of patients with a high mortality rate worldwide. Many of these cardiovascular pathologies, during their development, generate a state of oxidative stress that leads to a deterioration in the patient’s conditions associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Within these reactive species we find superoxide anion (O2•–), hydroxyl radical (•OH), nitric oxide (NO•), as well as other species of non-free radicals such as hydrogen peroxide (H2O2), hypochlorous acid (HClO) and peroxynitrite (ONOO–). A molecule that actively participates in counteracting the oxidizing effect of reactive species is reduced glutathione (GSH), a tripeptide that is present in all tissues and that its synthesis and/or regeneration is very important to be able to respond to the increase in oxidizing agents. In this review, we will address the role of glutathione, its synthesis in both the heart and the liver, and its importance in preventing or reducing deleterious ROS effects in cardiovascular diseases.

scholarly journals Ginkgo biloba extract (EGb 761) attenuates oxidative stress induction in erythrocytes of sickle cell disease patients

2012 ◽  
Vol 48 (4) ◽  
pp. 659-665 ◽  
Author(s):  
Aline Emmer Ferreira Furman ◽  
Railson Henneberg ◽  
Priscila Bacarin Hermann ◽  
Maria Suely Soares Leonart ◽  
Aguinaldo José do Nascimento
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Lipid Peroxidation ◽  
Sickle Cell ◽  
Reduced Glutathione ◽  
Reactive Oxygen ◽  
Intracellular Reactive Oxygen Species ◽  
Oxygen Species ◽  
Egb 761 ◽  
Cell Disease

Sickle cell disease promotes hemolytic anemia and occlusion of small blood vessels due to the presence of high concentrations of hemoglobin S, resulting in increased production of reactive oxygen species and decreased antioxidant defense capacity. The aim of this study was to evaluate the protective action of a standardized extract of Ginkgo biloba (EGb 761), selected due to its high content of flavonoids and terpenoids, in erythrocytes of patients with sickle cell anemia (HbSS, SS erythrocytes) subjected to oxidative stress using tert-butylhydroperoxide or 2,2-azobis-(amidinepropane)-dihydrochloride, in vitro. Hemolysis indexes, reduced glutathione, methemoglobin concentrations, lipid peroxidation, and intracellular reactive oxygen species were determined. SS erythrocytes displayed increased rates of oxidation of hemoglobin and membrane lipid peroxidation compared to normal erythrocytes (HbAA, AA erythrocytes), and the concentration of EGb 761 necessary to achieve the same antioxidant effect in SS erythrocytes was at least two times higher than in normal ones, inhibiting the formation of intracellular reactive oxygen species (IC50 of 13.6 µg/mL), partially preventing lipid peroxidation (IC50 of 242.5 µg/mL) and preventing hemolysis (IC50 of 10.5 µg/mL). Thus, EGb 761 has a beneficial effect on the oxidative status of SS erythrocytes. Moreover, EGb 761 failed to prevent oxidation of hemoglobin and reduced glutathione at the concentrations examined.

Reperfusion injury on cardiac myocytes after simulated ischemia

1996 ◽  
Vol 270 (4) ◽  
pp. H1334-H1341 ◽  
Author(s):  
T. L. Vanden Hoek ◽  
Z. Shao ◽  
C. Li ◽  
R. Zak ◽  
P. T. Schumacker ◽  
...  
Keyword(s):  
Cell Death ◽  
Reperfusion Injury ◽  
Cell Injury ◽  
Membrane Damage ◽  
Cardiac Injury ◽  
Cellular Membrane ◽  
Iodide Uptake ◽  
Membrane Injury ◽  
Simulated Ischemia ◽  
Lactate Dehydrogenase Release

The extent of cardiac injury incurred during reperfusion as opposed to that occurring during ischemia is unclear. This study tested the hypothesis that simulated ischemia followed by simulated reperfusion causes significant "reperfusion injury" in isolated chick cardiomyocytes. Cells were exposed to hypoxia, hypercarbic acidosis, hyperkalemia, and substrate deprivation for 1 h followed by 3 h of reperfusion. Irreversible cell membrane injury, measured by propidium iodide uptake, increased from 4% of cells at the end of ischemia to 73% after reperfusion; death occurred in only 17% of cells kept ischemic for 4 h. Lactate dehydrogenase release was consistent with these changes. Lengthening ischemia from 30 to 90 min increased cell injury as expected, but of the total cell death, > 90% occurred during reperfusion. "Chemical hypoxia" composed of cyanide (2.5 mM) plus 2-deoxyglucose augmented injury before reperfusion compared with simulated ischemia. Inhibition of oxygen radical generation by use of metal chelator 1,10-phenanthroline reduced cell death from 73% to 40% after reperfusion (P = 0.001). We conclude that simulated reperfusion significantly augments the cellular membrane damage elicited by simulated ischemia in isolated cardiomyocytes devoid of other factors and suggest that reactive oxygen species, perhaps from the mitochondria, participate in this injury.

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