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 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.

Nose-only water-pipe smoking effects on airway resistance, inflammation, and oxidative stress in mice

2013 ◽  
Vol 115 (9) ◽  
pp. 1316-1323 ◽  
Author(s):  
Abderrahim Nemmar ◽  
Haider Raza ◽  
Priya Yuvaraju ◽  
Sumaya Beegam ◽  
Annie John ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Airway Resistance ◽  
Reduced Glutathione ◽  
Mechanistic Explanation ◽  
The United States ◽  
Forced Oscillation Technique ◽  
Water Pipe ◽  
Respiratory Effects ◽  
And Oxidative Stress

Water-pipe smoking (WPS) is a common practice in the Middle East and is now gaining popularity in Europe and the United States. However, there is a limited number of studies on the respiratory effects of WPS. More specifically, the underlying pulmonary pathophysiological mechanisms related to WPS exposure are not understood. Presently, we assessed the respiratory effects of nose-only exposure to mainstream WPS generated by commercially available honey flavored “moasel ” tobacco. The duration of the session was 30 min/day and 5 days/wk for 1 mo. Control mice were exposed to air only. Here, we measured in BALB/c mice the airway resistance using forced-oscillation technique. Lung inflammation was assessed histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid, and oxidative stress was evaluated biochemically by measuring lipid peroxidation, reduced glutathione and several antioxidant enzymes. Pulmonary inflammation assessment showed an increase in neutrophil and lymphocyte numbers. Likewise, airway resistance was significantly increased in the WPS group compared with controls. Tumor necrosis factor α and interleukin 6 concentrations were significantly increased in BAL fluid. Lipid peroxidation in lung tissue was significantly increased whereas the level and activity of antioxidants including reduced glutathione, glutathione S transferase, and superoxide dismutase were all significantly decreased following WPS exposure, indicating the occurrence of oxidative stress. Moreover, carboxyhemoglobin levels were significantly increased in the WPS group. We conclude that 1-mo nose-only exposure to WPS significantly increased airway resistance, inflammation, and oxidative stress. Our results provide a mechanistic explanation for the limited clinical studies that reported the detrimental respiratory effects of WPS.

Reduction of doxorubicin-induced cytotoxicity and mitochondrial damage by betanin in rat isolated cardiomyocytes and mitochondria

2021 ◽  
pp. 096032712110228
Author(s):  
AA Hafez ◽  
Z Jamali ◽  
S Samiei ◽  
S Khezri ◽  
A Salimi
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Bioactive Compound ◽  
Isolated Cardiomyocytes ◽  
Cardiac Inflammation ◽  
Flow Cytometric ◽  
Significant Toxicity ◽  
Ros Formation ◽  
Gene Regulatory ◽  
And Oxidative Stress

Doxorubicin (DOX) is an anticancer drug which is used for treatment of several types of cancers. But the clinical use of doxorubicin is limited because of its cardiotoxicity and cardiomyopathy. Mitochondrial-dependent oxidative stress and cardiac inflammation appear to be involved in doxorubicin-induced cardiotoxicity. Betanin as a bioactive compound in Beetroot ( Beta vulgaris L.) displays anti-radical, antioxidant gene regulatory and cardioprotective activities. In this current study, we investigated the protective effect of betanin on doxorubicin-induced cytotoxicity and mitochondrial-dependent oxidative stress in isolated cardiomyocytes and mitochondria. Isolated cardiomyocytes and mitochondria were treated with three concentrations of betanin (1, 5 and 10 µM) and doxorubicin (3.5 µM) for 6 h. The parameters of cellular and mitochondrial toxicity were analyzed using biochemical and flow cytometric methods. Our results showed a significant toxicity in isolated cardiomyocytes and mitochondria in presence of doxorubicin which was related to reactive oxygen species (ROS) formation, increase in malondialdehyde (MDA), increase in oxidation of GSH to GSSG, lysosomal/mitochondrial damages and mitochondrial swelling. While betanin pretreatment reverted doxorubicin-induced cytotoxicity and oxidative stress in isolated cardiomyocytes and mitochondria. These results suggest that betanin elicited a typical protective effect on doxorubicin-induced cytotoxicity and oxidative stress. It is possible that betanin could be used as a useful adjuvant in combination with doxorubicin chemotherapy for reduction of cardiotoxicity and cardiomyopathy.

scholarly journals Protective Role of UCP2 in Oxidative Stress and Apoptosis during the Silent Phase of an Experimental Model of Epilepsy Induced by Pilocarpine

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Marina Rascio Henriques Dutra ◽  
Regiane dos Santos Feliciano ◽  
Kalil Ribeiro Jacinto ◽  
Telma Luciana Furtado Gouveia ◽  
Eduardo Brigidio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Role ◽  
Negative Regulator ◽  
Antioxidant Enzyme Activities ◽  
Ucp2 Expression ◽  
Silent Phase ◽  
Ros Formation ◽  
Neuroprotective Actions ◽  
And Oxidative Stress

Neuroprotection is a desirable process in many neurological disorders, yet complex mechanisms involved in this field are not completely understood. The pilocarpine epilepsy model causes potent, seizure-induced excitotoxicity cell death and mitochondria impairment. The present study is aimed at investigating the role of UCP2, a ROS negative regulator, in the neuroprotection after cholinergic insult. Our data demonstrated that UCP2 expression was augmented in the rat hippocampus 3 days after status epilepticus (SE), reaching a peak on the fifth day, then returning to basal levels. Concomitantly, phospho-AKT expression levels were higher in the hippocampus during the early silent phase (5 days after SE). Additionally, it was demonstrated that the blockade of UCP2 by antisense oligonucleotides (ASO) in SE rats successfully diminished both UCP2 mRNA and protein contents. SE ASO rats presented increased mitochondrial proapoptotic factor expression, caspase-3 activity, inflammatory cytokine expression, and ROS formation. Moreover, ASO treatment diminished p-AKT expression and antioxidant enzyme activities after pilocarpine insult. In conclusion, the present results highlight the neuroprotective actions of UCP2, acting in the inhibition of apoptotic factors and oxidative stress, to increase neuron survival after SE onset.

scholarly journals Sodium para-aminosalicylic acid inhibits manganese-induced NLRP3 inflammasome-dependent pyroptosis by inhibiting NF-κB pathway activation and oxidative stress

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Dongjie Peng ◽  
Junyan Li ◽  
Yue Deng ◽  
Xiaojuan Zhu ◽  
Lin Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Basal Ganglia ◽  
Mitochondrial Membrane Potential ◽  
Nlrp3 Inflammasome ◽  
Mitochondrial Membrane ◽  
Aminosalicylic Acid ◽  
Pathway Activation ◽  
Bv2 Cells ◽  
And Oxidative Stress

Abstract Background The activation of NOD-like receptor protein 3 (NLRP3) inflammasome-dependent pyroptosis has been shown to play a vital role in the pathology of manganese (Mn)-induced neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has a positive effect on the treatment of manganism. However, the mechanism is still unclear. We hypothesized that PAS-Na might act through NLRP3. Methods The microglial cell line BV2 and male Sprague-Dawley rats were used to investigate the impacts of PAS-Na on Mn-induced NLRP3 inflammasome-dependent pyroptosis. The related protein of the NF-κB pathway and NLRP3-inflammasome-dependent pyroptosis was detected by western blot. The reactive oxygen species and mitochondrial membrane potential were detected by immunofluorescence staining and flow cytometry. The activation of microglia and the gasdermin D (GSDMD) were detected by immunofluorescence staining. Results Our results showed that Mn treatment induced oxidative stress and activated the NF-κB pathway by increasing the phosphorylation of p65 and IkB-α in BV2 cells and in the basal ganglia of rats. PAS-Na could alleviate Mn-induced oxidative stress damage by inhibiting ROS generation, increasing mitochondrial membrane potential and ATP levels, thereby reducing the phosphorylation of p65 and IkB-α. Besides, Mn treatment could activate the NLRP3 pathway and promote the secretion of IL-18 and IL-1β, mediating pyroptosis in BV2 cells and in the basal ganglia and hippocampus of rats. But an inhibitor of NF-κb (JSH-23) treatment could significantly reduce LDH release, the expression of NLRP3 and Cleaved CASP1 protein and IL-1β and IL-18 mRNA level in BV2 cells. Interestingly, the effect of PAS-Na treatment in Mn-treated BV2 cells is similar to those of JSH-23. Besides, immunofluorescence results showed that PAS-Na reduced the increase number of activated microglia, which stained positively for GSDMD. Conclusion PAS-Na antagonized Mn-induced NLRP3 inflammasome dependent pyroptosis through inhibiting NF-κB pathway activation and oxidative stress.

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