scholarly journals Cytotoxic, genotoxic, and oxidative stress-related effects of lysergic acid diethylamide (LSD) and phencyclidine (PCP) in the human neuroblastoma SH-SY5Y cell line

2021 ◽  
Vol 72 (4) ◽  
pp. 333-342
Author(s):  
Andreja Jurič ◽  
Antonio Zandona ◽  
Blanka Tariba Lovaković ◽  
Dubravka Rašić ◽  
Alica Pizent ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Negative Control ◽  
Lysergic Acid ◽  
Lysergic Acid Diethylamide ◽  
Control Treatment ◽  
Human Neuroblastoma ◽  
Biochemical Assays ◽  
And Oxidative Stress ◽  
Primary Dna Damage

Abstract Lysergic acid diethylamide (LSD) is a classic hallucinogen, widely abused for decades, while phencyclidine (PCP) has increased in popularity in recent years, especially among the adolescents. Very little is known about the general toxicity of these compounds, especially about their possible neurotoxic effects at the cell level. The aim of this study was to address these gaps by assessing the toxic effects of 24-hour exposure to LSD and PCP in the concentration range of 0.39–100 μmol/L in the human neuroblastoma SH-SY5Y cell line. After cell viability was established, cells treated with concentrations that reduced their viability up to 30 % were further subjected to the alkaline comet assay and biochemical assays that enable estimation of oxidative stress-related effects. Treatment with LSD at 6.25 μmol/L and with PCP at 3.13 μmol/L resulted with 88.06±2.05 and 84.17±3.19 % of viable cells, respectively, and led to a significant increase in primary DNA damage compared to negative control. LSD also caused a significant increase in malondialdehyde level, reactive oxygen species (ROS) production, and glutathione (GSH) level, PCP significantly increased ROS but lowered GSH compared to control. Treatment with LSD significantly increased the activities of all antioxidant enzymes, while PCP treatment significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) but decreased catalase (CAT) activity compared to control. Our findings suggest that LSD has a greater DNA damaging potential and stronger oxidative activity than PCP in SH-SY5Y cells.

scholarly journals Genomic Adaption and Mutational Patterns in a HaCaT Subline Resistant to Alkylating Agents and Ionizing Radiation

2021 ◽  
Vol 22 (3) ◽  
pp. 1146
Author(s):  
Reinhard Ullmann ◽  
Benjamin Valentin Becker ◽  
Simone Rothmiller ◽  
Annette Schmidt ◽  
Horst Thiermann ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Copy Number ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Chromosomal Translocations ◽  
Dna Copy Number ◽  
Mutational Signatures ◽  
Copy Number Changes ◽  
And Oxidative Stress

Sulfur mustard (SM) is a chemical warfare agent that can damage DNA via alkylation and oxidative stress. Because of its genotoxicity, SM is cancerogenic and the progenitor of many chemotherapeutics. Previously, we developed an SM-resistant cell line via chronic exposure of the popular keratinocyte cell line HaCaT to increasing doses of SM over a period of 40 months. In this study, we compared the genomic landscape of the SM-resistant cell line HaCaT/SM to its sensitive parental line HaCaT in order to gain insights into genetic changes associated with continuous alkylation and oxidative stress. We established chromosome numbers by cytogenetics, analyzed DNA copy number changes by means of array Comparative Genomic Hybridization (array CGH), employed the genome-wide chromosome conformation capture technique Hi-C to detect chromosomal translocations, and derived mutational signatures by whole-genome sequencing. We observed that chronic SM exposure eliminated the initially prevailing hypotetraploid cell population in favor of a hyperdiploid one, which contrasts with previous observations that link polyploidization to increased tolerance and adaptability toward genotoxic stress. Furthermore, we observed an accumulation of chromosomal translocations, frequently flanked by DNA copy number changes, which indicates a high rate of DNA double-strand breaks and their misrepair. HaCaT/SM-specific single-nucleotide variants showed enrichment of C > A and T > A transversions and a lower rate of deaminated cytosines in the CpG dinucleotide context. Given the frequent use of HaCaT in toxicology, this study provides a valuable data source with respect to the original genotype of HaCaT and the mutational signatures associated with chronic alkylation and oxidative stress.

scholarly journals Rapamycin attenuated zinc-induced tau phosphorylation and oxidative stress in animal model: Involvement of dual mTOR/p70S6K and Nrf2/HO-1 pathways

2021 ◽  
Author(s):  
Chencen Lai ◽  
Qian Chen ◽  
Yuanting Ding ◽  
Songbai Su ◽  
Heng Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Morris Water Maze ◽  
Zinc Sulfate ◽  
Water Maze ◽  
Tau Phosphorylation ◽  
Alzheimers Disease ◽  
Tau Pathology ◽  
Biochemical Assays ◽  
And Oxidative Stress

Alzheimers disease is pathologically featured by abnormal accumulation of amyloid-beta plaque, neurofibrillary tangles, oxidative stress, neuroinflammation, and neurodegeneration. Metal dysregulation including excessive zinc released by presynaptic neurons plays an important role in tau pathology and oxidase activation. The activities of mammalian target of rapamycin (mTOR)/ ribosomal S6 protein kinase (p70S6K) are elevated in the brains of patients with Alzheimers disease. Zinc induces tau hyperphosphorylation via mTOR/P70S6K activation in vitro. However, the involvement of mTOR/P70S6K pathway in zinc-induced oxidative stress, tau degeneration, synaptic and cognitive impairment, has not been fully elucidated in vivo. Here we assessed in the effect of pathological concentration of zinc in SH-SY5Y cells by using biochemical assays and immunofluorescence staining. Rats (n = 18, male) were lateral ventricularly-injected with zinc and treated with rapamycin (intraperitoneal injection) for one week and assessed using Morris water maze. Evaluation of the oxidative stress, tau phorsphylation and synaptic impairment were performed using the hippocampus tissue of the rats by biochemical assays and immunofluorescence staining. Results from Morris water maze showed that the capacity of spatial memory is impaired in zinc-treated rats. Zinc sulfate significantly increased the levels of P-mTOR Ser2448, P-p70S6K Thr389, and P-tau Ser356, and decreased levels of Nrf2 and HO-1 in SH-SY5Y cells and in zinc-treated rats compared with control groups. Increased expressions of reactive oxygen species were observed in zinc sulfate-induced SH-SY5Y cells as well as in the hippocampus of zinc-injected rats. Rapamycin, an inhibitor of mTOR, rescued the zinc-induced increases in mTOR/p70S6K activations, tau phosphorylation and oxidative stress, as well as Nrf2/HO-1 inactivation, cognitive impairment and synaptic impairment reduced the expression of synapse-related proteins in zinc-injected rats. In conclusion, our findings imply that rapamycin prevents zinc-induced cognitive impairment and protects neurons from tau pathology, oxidative stress and synaptic impairment, by decreasing mTOR/p70S6K hyperactivity and increasing Nrf2/HO-1 activity.

scholarly journals GAMBARAN HISTOPATOLOGI PARU TIKUS WISTAR SETELAH DIBERI PAPARAN ASAP ROKOK

2018 ◽  
Vol 2 (2) ◽  
Author(s):  
Novera Herdiani ◽  
Endah Budi Permana Putri
Keyword(s):  
Oxidative Stress ◽  
Alveolar Macrophage ◽  
Cigarette Smoke ◽  
Wistar Rats ◽  
Positive Control ◽  
Negative Control ◽  
Control Treatment ◽  
Rat Lung ◽  
Dragon Fruit ◽  
Lung Histopathology

Abstract: Cigarette smoke is the main cause of lung obstruction. One of the obstructions in real that iscaused by cigarette smoke is oxidative stress. Oxidative stress trigger inflammation response occur andlung obstruction. Cigarette smoke able to cause lung histopathology changes like lungs obstruction onalveolus wall. Red dragon fruit extract tackle free radical then able to against the oxidative stress. Theobjective of this study to examines the image of rat lung histopathology under exposed cigarette smoke.Twenty four Wistar rats divided four groups: negative control, positive control, red dragon fruit extracttreatment of 7,2 g/200 g WB, and red dragon fruit extract10,8 g/200 g WB. Negative control only givenstandard feed. Positive control given standar feed and exposed 21 cigarette per day. Treatment groupgiven feed during 21 days. In the 22nd day rats be sacrificed, the lung taken out for observation andimage of rat lung histopathology changes by making lung organ histopathology preparationhematoxicillin Eosion (HE) staining and observed under magnification light microscope 400x. The endresult of the study indicate the finding of changes in lung histopathology such as obstruction level overthe lung tissue higher, alveolar macrophage covered alveoli after being exposed cigarette smoke. Groupwhich does not exposed cigarette smoke, lung alveolus macrophage in normal condition, there are noobstruction or alveolus macrophage occurred, its alveolar macrophage does no covering alveoli.Treatment group administered fruit dragon extract dose 10,8 g/200 g WB and dose 7,2 g/200 g WB seemalmost the same with negative control treatment. Conclusion of the research is cigarette smoke exposecan influence the number of alveolar macrophage on wistar rats. Suggestion very required furtherresearch on oxdative stress parameter.

Cartap-induced cytotoxicity in mouse C2C12 myoblast cell line and the roles of calcium ion and oxidative stress on the toxic effects

Toxicology ◽  
2006 ◽  
Vol 219 (1-3) ◽  
pp. 73-84 ◽  
Author(s):  
Jiunn-Wang Liao ◽  
Jaw-Jou Kang ◽  
Chian-Ren Jeng ◽  
Shao-Kuang Chang ◽  
Ming-Jang Kuo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Calcium Ion ◽  
Toxic Effects ◽  
C2c12 Myoblast ◽  
Myoblast Cell Line ◽  
Myoblast Cell ◽  
And Oxidative Stress
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