scholarly journals Protective Effect of Capparis spinosa Extract against Potassium Bromate Induced Oxidative Stress and Genotoxicity in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Khalid Mashai Al-Anazi ◽  
Ali Abdullah Al-Mareed ◽  
Mohammed Abul Farah ◽  
M. Ajmal Ali ◽  
Waleed A. Q. Hailan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Dna Damage ◽  
Annexin V ◽  
Protective Role ◽  
Potassium Bromate ◽  
Dependent Manner ◽  
Protective Effects ◽  
Treatment Groups ◽  
Apoptosis Assay ◽  
Capparis Spinosa

Despite the commercial value of potassium bromate (KBrO3), it has been linked to many diseases including cancer. Capparis spinosa possesses exceptional ethnobotanical, pharmaceutical, and economic prominence by virtue of its bioactive components. The present study was designed to explore the protective role and antioxidant potential of ethanolic leaves extract of C. spinosa against the oxidative stress, genotoxicity, and apoptosis induced by KBrO3 in an experimental animal model. The results of the study revealed remarkable diminution in the levels of oxidative stress in all the treatment groups. C. spinosa extract attenuated the toxic effects of KBrO3 significantly ( p  < 0.05) in a time- and dose-dependent manner by restoring the normal levels of ROS and antioxidative enzymes in serum and liver tissues. The extract also abolished the oxidative DNA damage as it was evident in decreased frequency of micronuclei. A marked increase in viable cells was observed in annexin-V apoptosis assay. In conclusion, the findings of the present study demonstrate that ethanolic leaves extract of C. spinosa has considerable protective effects against KBrO3-induced toxicity in experimental mice which is attributed to its antioxidant activity. Therefore, leaves of C. spinosa could be used as a potential source of natural antioxidant and bioactive compounds.

scholarly journals Pharmacological and biochemical studies on the protective effects of melatonin during stress-induced behavioral and immunological changes in relation to oxidative stress in rats

2016 ◽  
Vol 94 (3) ◽  
pp. 296-301 ◽  
Author(s):  
Rishi Pal ◽  
Kavita Gulati ◽  
B.D. Banerjee ◽  
Arunabha Ray
Keyword(s):  
Oxidative Stress ◽  
Brain Homogenate ◽  
Protective Role ◽  
Dependent Manner ◽  
Protective Effects ◽  
Immunological Parameters ◽  
Stress Markers ◽  
Test Parameters ◽  
Neuropsychiatric Diseases ◽  
Immunological Changes

Stress is known to precipitate neuropsychiatric diseases, and depending upon its nature and intensity it can also influence the functioning of the immune system. Melatonin (N-acetyl-5-methoxy tryptamine) a pineal gland hormone and potent antioxidant is known to protect against many diseases. Effect of melatonin in stress-induced neuro-immunomodulation is not well elucidated. Therefore in the present study, the protective effects of melatonin were evaluated in restraint stress (RS)-induced behavioral and immunological changes in rats. RS for 1 h significantly reduces (i) percentage of open-arm entries and (ii) percentage of time spent on open-arm in elevated plus maze (EPM) test parameters (p < 0.01) and significant increase in MDA levels in brain homogenate when compared to non-RS control groups (p < 0.05). In immunological studies, both humoral and cell-mediated immune responses to antigen were significantly suppressed by RS for 1 h for 5 consecutive days, as evidenced by significant reduction in (i) anti-SRBC antibody titre, (ii) PFC counts, (iii) percentage change in paw volume, and (iv) Th1 (IFN-γ) and Th2 (IL-4) cytokine levels (p < 0.001 in all parameters). These RS-induced immunological changes were associated with significantly increased lipid peroxidation (MDA) levels in serum and significantly decreased activity of (i) SOD, (ii) CAT, and (iii) GSH levels in RS (X5)-exposed group (p < 0.02). Pretreatment with melatonin (10, 50, and 100 mg/kg) significantly reversed these RS-induced changes in EPM test parameters and humoral and cell-mediated immunological parameters, as well as oxidative stress markers in a dose-dependent manner by differential degrees (p < 0.001). Results are strongly suggestive of the involvement of free radicals during stress-induced neurobehavioral and immunological changes. These changes were significantly restored by melatonin pretreatment. We can conclude that melatonin may have a protective role during such stress-induced neuro-immunomodulation.

scholarly journals Probucol Protects Rats from Cardiac Dysfunction Induced by Oxidative Stress following Cardiopulmonary Resuscitation

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xu Xiao ◽  
Huiyuan Hou ◽  
Victor Lin ◽  
Daisy Ho ◽  
Kyle Tran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiopulmonary Resuscitation ◽  
Survival Time ◽  
Spontaneous Circulation ◽  
Antioxidant Enzyme Activities ◽  
Dependent Manner ◽  
Protective Effects ◽  
Hemodynamic Parameters ◽  
Sprague Dawley ◽  
Treatment Groups

Objective. To investigate the protective effect of probucol on induced cardiac arrest (CA) rats and possible mechanisms.Methods. Sprague Dawley rats were orally administrated with probucol at different dosage or vehicle for 5 days and subjected to a CA model by electrical stimulation, followed by cardiopulmonary resuscitation (CPR). The return of spontaneous circulation (ROSC) rate, antioxidant enzyme activities, and lipid oxidation markers were measured in serum and myocardium. Hemodynamic parameters and myocardial functions of animals were analyzed. Expression of erythroid-derived 2-like 2 (NFE2L2) and Kelch-like ECH-associated protein 1 (KEAP1) in the myocardium were examined with immunohistochemistry.Results. Probucol treatment significantly increased the ROSC rate and survival time of CA-induced rats. After ROSC, levels of oxidation-specific markers were decreased, while activities of antioxidant enzymes were increased significantly in probucol treatment groups. The probucol treatment improves hemodynamic parameters and myocardial functions. These parameter changes were in a dose-dependent manner. In the probucol treatment groups, the expression of KEAP1 was downregulated, while that of NFE2L2 was upregulated significantly.Conclusion. In the CA-induced rat model, probucol dose dependently improved the ROSC rate, prolonged survival time, alleviated oxidative stress, and improved cardiac function. Such protective effects are possibly through regulations of the KEAP1-NFE2L2 system.

Combination of Histone Deacetylase Inhibitor with Cu(II) 5,5- diethylbarbiturate Complex Induces Apoptosis in Breast Cancer Stem Cells: A Promising Novel Approach

2020 ◽  
Vol 21 ◽  
Author(s):  
Merve Erkisa ◽  
Nazlihan Aztopal ◽  
Elif Erturk ◽  
Engin Ulukaya ◽  
Veysel T. Yilmaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Histone Deacetylases ◽  
Caspase 3 ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Tumor Formation ◽  
Dependent Manner

Background: Cancer stem cells (CSC) are subpopulation within the tumor that acts a part in the initiation, progression, recurrence, resistance to drugs and metastasis of cancer. It is well known that epigenetic changes lead to tumor formation in cancer stem cells and show drug resistance. Epigenetic modulators and /or their combination with different agents have been used in cancer therapy. Objective: In our study we scope out the effects of combination of a histone deacetylases inhibitor, valproic acid (VPA), and Cu(II) complex [Cu(barb-κN)(barb-κ2N,O)(phen-κN,N’)]·H2O] on cytotoxicity/apoptosis in a stem-cell enriched population (MCF-7s) obtained from parental breast cancer cell line (MCF-7). Methods: Viability of the cells was measured by the ATP assay. Apoptosis was elucidated via the assessment of caspase-cleaved cytokeratin 18 (M30 ELISA) and a group of flow cytometry analysis (caspase 3/7 activity, phosphatidylserine translocation by annexin V-FITC assay, DNA damage and oxidative stress) and 2ˈ,7ˈ–dichlorofluorescein diacetate staining. Results: The VPA combined with Cu(II) complex showed anti proliferative activity on MCF-7s cells in a dose- and time-dependently. Treatment with combination of 2.5 mM VPA and 3.12 μM Cu(II) complex induces oxidative stress in a time-dependent manner, as well as apoptosis that is evidenced by the increase in caspase 3/7 activity, positive annexin-V-FITC, and increase in M30 levels. Conclusion: The results suggest that the combination therapy induces apoptosis following increased oxidative stress, thereby making it a possible promising therapeutic strategy that further analysis is required.

scholarly journals Concentration-Dependent Antioxidant/Pro-Oxidant Activity of Ascorbic Acid in Chickens

2012 ◽  
Vol 66 (6) ◽  
pp. 256-260
Author(s):  
Nadežda Berzina ◽  
Jurijs Markovs ◽  
Mirdza Apsīte ◽  
Svetlana Vasiļjeva ◽  
Galina Smirnova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ascorbic Acid ◽  
Cadmium Concentration ◽  
Dehydroascorbic Acid ◽  
Cadmium Accumulation ◽  
Suppressive Effect ◽  
High Dose ◽  
Dependent Manner ◽  
Treatment Groups ◽  
Liver And Kidney

The effects of ascorbic acid supplementation on biomarkers of oxidative stress, cadmium accumulation in organs, immune system activity and kidney function in chickens were investigated. The treatment groups of chickens were fed either plain diet or diet supplemented with ascorbic acid at 100, 500, 1000 and 2000 mg/kg for four weeks. Liver and kidney tissues were assayed for cadmium concentration, and the hepatic levels of ascorbic acid and dehydroascorbic acid (DHAA; the oxidised form), malondialdehyde, glutathione, activity of glutathione peroxidase, blood serum uric acid, creatinine, lysozyme and circulating immune complexes were measured. Supplementation with a high dose of ascorbic acid (1000 and 2000 mg/kg in the diet) caused an imbalance between pro-oxidative and antioxidative activities, and induced a suppressive effect on innate immunity. The results suggest that oxidative stress compromises renal function. We observed that ascorbic acid increased cadmium accumulation in a dose-dependent manner.

ID: 140: KLOTHO, AN ANTI-AGING MOLECULE, REGULATES ALVEOLAR EPITHELIAL CELL MTDNA DAMAGE AND APOPTOSIS

2016 ◽  
Vol 64 (4) ◽  
pp. 961.1-961
Author(s):  
S Kim ◽  
P Cheresh ◽  
RP Jablonski ◽  
DW Kamp ◽  
M Eren ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Oxidative Dna Damage ◽  
Alveolar Epithelial Cell ◽  
Premature Aging ◽  
Protective Effects ◽  
Mtdna Damage ◽  
Alveolar Epithelial

RationaleConvincing evidence has emerged that impaired alveolar epithelial cell (AEC) injury and repair resulting from ‘exaggerated’ lung aging and mitochondrial dysfunction are critical determinants of the lung fibrogenic potential of toxic agents, including asbestos fibers, but the mechanisms underlying these findings is unknown. We showed that the extent of AEC mitochondrial DNA (mtDNA) damage and apoptosis are critical determinants of asbestos-induced pulmonary fibrosis (Cheresh et al AJRCMB 2014, Kim et al JBC 2014). Klotho is an age-inhibiting gene and Klotho-deficient mice demonstrate a premature aging phenotype that includes a reduced lifespan, arteriosclerosis, and lung oxidative DNA damage, and that Klotho attenuates hyperoxic-induced AEC DNA damage and apoptosis (Ravikumar et al AJP-Lung 2014). We reason that Klotho has an important role in limiting pulmonary fibrosis by protecting the AECs from oxidative stress.MethodsQuantitative PCR-based measurement of mtDNA damage was assessed following transient transfection with wild-type Klotho, Klotho siRNA or AKT siRNA in A549 and/or MLE-12 cells for 48 hrs followed by exposure to either amosite asbestos (25 µg/cm2) or H2O2 (200 µM) for 24 hrs. Apoptosis was assessed by cleaved caspase-9/3 levels and DNA fragmentation assay. Murine pulmonary fibrosis was analyzed in male 8–10 week old WT (C3H/C57B6J) mice or Klotho heterozygous knockout (Kl+/−) mice following intratracheal instillation of a single dose of 100 µg crocidolite asbestos or titanium dioxide (negative control) using histology (fibrosis score by Masson's trichrome staining) and lung collagen (Sircoll assay).ResultsCompared to control, amosite asbestos or H2O2 reduces Klotho mRNA/protein expression. Notably, silencing of Klotho promotes oxidative stress-induced AEC mtDNA damage and apoptosis whereas Klotho-enforced expression (EE) and Euk-134, a mitochondrial ROS scavenger, are protective. Interestingly, Kl+/− mice have increased asbestos-induced lung fibrosis. Also, we find that inhibition or silencing of AKT augments oxidant-induced AEC mtDNA damage and apoptosis.ConclusionsOur data demonstrate a crucial role for AEC AKT signaling in mediating the mtDNA damage protective effects of Klotho. Given the importance of AEC aging and apoptosis in pulmonary fibrosis, we reason that Klotho/AKT axis is an innovative therapeutic target for preventing common lung diseases of aging (i.e. IPF, COPD, lung cancer, etc.) for which more effective management regimens are clearly needed.FundingNIH-RO1 ES020357-01A1 (DK) and VA Merit (DK).

Protective role of vitamins A, C, and E against the genotoxic damage induced by aflatoxin B1 in cultured human lymphocytes

2009 ◽  
Vol 25 (3) ◽  
pp. 183-188 ◽  
Author(s):  
L Alpsoy ◽  
G Agar ◽  
M Ikbal
Keyword(s):  
Vitamin A ◽  
Vitamin C ◽  
Human Lymphocytes ◽  
Mutagenic Effect ◽  
Treated Group ◽  
Protective Role ◽  
Effective Concentration ◽  
Dependent Manner ◽  
Protective Effects ◽  
Aflatoxin B

In this study, we aimed to evaluate the effect of vitamins A, C, and E against aflatoxin B1 (AFB1) on blood cultures in relation to induction of sister chromatid exchange (SCE). The results indicated genotoxic and mutagenic damage in cultured human lymphocytes exposed to AFB1. The results showed that 5 μM concentration of AFB1 increased SCE. When vitamins A, C, and E were added to AFB1, the frequency of SCE decreased. These results suggest that vitamins A, C, and E could effectively inhibit AFB1-induced SCE, which may partially responsible for its mutagenic effect of AFB1. Besides, the protective effect of vitamins A, C, and E against AFB1 was increased in a dose-dependent manner (i.e., as the doses increased, their protective effects also increased). There was a significant decrease in the SCE frequency in AFB1-treated group compared with the groups receiving AFB1 and also vitamins A, C, and E. The most effective concentration was 100 microM vitamin C, and the lowest effective concentration was 0.5 microM vitamin A. Vitamin C has the most effective concentration of 100 μM, and vitamin A has the lowest effective concentration of 0.5 μM. The order of the decreasing effect of the SCE frequency of vitamins was as follows: vitamin C > vitamin E > vitamin A.

scholarly journals Triptolide Attenuates Vascular Calcification by Upregulating Expression of miRNA-204

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu-qiang Pei ◽  
Yong-qiu Zheng ◽  
Yao-dong Ding ◽  
Qi-xiang Xu ◽  
Di Cao ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Calcium Content ◽  
Rat Aorta ◽  
Protective Role ◽  
Bone Morphogenetic Protein 2 ◽  
Dependent Manner ◽  
Protective Effects ◽  
Alp Activity

Background: Triptolide (TP), a naturally derived compound from Tripterygium wilfordii, has been proven effective in protecting against cardiovascular system, but the molecular mechanisms underlying its protective effects are poorly understood. In the current study, we sought to test the potential protective role of TP in the regulation of vascular calcification in a rat model and explore whether TP attenuates medial vascular calcification by upregulating miRNA-204.Methods: Vitamin D3 plus nicotine (VDN) was used to induce a vascular calcification (VC) model of rat aorta. Von Kossa and Hematoxylin-Eosin staining were applied to assess the degree of calcification of rat aortas. Calcium content and alkaline phosphatase activity were measured. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was applied to quantify miRNA-204 expression. The localization of runt-related transcription factor-2 (RUNX2) and bone morphogenetic protein-2 (BMP2) expressions were detected by immunohistochemistry and western blotting.Results: Administration of TP greatly reduced vascular calcification in a dose-dependent manner compared with VC controls. The increase in ALP activity and calcium content was ameliorated by TP. Moreover, protein expression levels of BMP2 and RUNX2 were significantly reduced in calcified aortas. MiRNA-204 expression was increased in the TP-treated groups compared with VC controls and the effects of TP were reversed by the intravenous injection of miRNA-204-interfering lentivirus. However, the miRNA-204-overexpressing lentivirus had no additional effects on ALP activity, calcium content, BMP2 and RUNX2 expressions compared with those from TP group.Conclusion: TP inhibited BMP2 and RUNX2 expression and attenuated vascular calcification via upregulating the level of miRNA-204. TP appears to be a potential new therapeutic option for treating vascular calcification.

scholarly journals Isoliquiritigenin Ameliorates Acute Pancreatitis in Mice via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Xinnong Liu ◽  
Qingtian Zhu ◽  
Min Zhang ◽  
Tao Yin ◽  
Rong Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Tissue Injury ◽  
Pancreatic Tissue ◽  
Zinc Protoporphyrin ◽  
Dependent Manner ◽  
Protective Effects ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Flavonoid Monomer

Oxidative stress plays a crucial role in the pathogenesis of acute pancreatitis (AP). Isoliquiritigenin (ISL) is a flavonoid monomer with confirmed antioxidant activity. However, the specific effects of ISL on AP have not been determined. In this study, we aimed to investigate the protective effect of ISL on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, dynamic changes in oxidative stress injury of the pancreatic tissue were observed after AP onset. We found that ISL administration reduced serum amylase and lipase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Meanwhile, ISL decreased the oxidative stress injury and increased the protein expression of the Nrf2/HO-1 pathway. In addition, after administering a Nrf2 inhibitor (ML385) or HO-1 inhibitor (zinc protoporphyrin) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of ISL on AP in mice. Furthermore, we found that ISL mitigated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by L-arginine. Taken together, our data for the first time confirmed the protective effects of ISL on AP in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway.

scholarly journals The Neuroprotective Effects ofRatanasampilon Oxidative Stress-Mediated Neuronal Damage in Human Neuronal SH-SY5Y Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Aiqin Zhu ◽  
Zhou Wu ◽  
Jie Meng ◽  
Patrick L. McGeer ◽  
Yi Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Mitogen Activated Protein Kinase ◽  
Tibetan Medicine ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Human Neuroblastoma ◽  
Traditional Tibetan Medicine

We previously found thatRatanasampil(RNSP), a traditional Tibetan medicine, improves the cognitive function of mild-to-moderate AD patients living at high altitude, as well as learning and memory in an AD mouse model (Tg2576); however, mechanism underlying the effects of RNSP is unknown. In the present study, we investigated the effects and molecular mechanisms of RNSP on oxidative stress-induced neuronal toxicity using human neuroblastoma SH-SY5Y cells. Pretreatment with RNSP significantly ameliorated the hydrogen peroxide- (H2O2-) induced cytotoxicity of SH-SY5Y cells in a dose-dependent manner (up to 60 μg/mL). Furthermore, RNSP significantly reduced the H2O2-induced upregulation of 8-oxo-2′-deoxyguanosine (8-oxo-dG, the oxidative DNA damage marker) but significantly reversed the expression of repressor element-1 silencing transcription factor (REST) from H2O2associated (100 μM) downregulation. Moreover, RNSP significantly attenuated the H2O2-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK 1/2) in SH-SY5Y cells. These observations strongly suggest that RNSP may protect the oxidative stress-induced neuronal damage that occurs through the properties of various antioxidants and inhibit the activation of MAPKs. We thus provide the principle molecular mechanisms of the effects of RNSP and indicate its role in the prevention and clinical management of AD.

scholarly journals Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPKα Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yan-Yan Meng ◽  
Yu-Pei Yuan ◽  
Xin Zhang ◽  
Chun-Yan Kong ◽  
Peng Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Cell Loss ◽  
Protective Role ◽  
Protective Effects ◽  
Morphological Examination ◽  
Heart Injury ◽  
Amp Activated Protein Kinase

Oxidative stress and cardiomyocyte apoptosis play critical roles in the development of doxorubicin- (DOX-) induced cardiotoxicity. Our previous study found that geniposide (GE) could inhibit cardiac oxidative stress and apoptosis of cardiomyocytes but its role in DOX-induced heart injury remains unknown. Our study is aimed at investigating whether GE could protect against DOX-induced heart injury. The mice were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce cardiomyopathy model. To explore the protective effects, GE was orally given for 10 days. The morphological examination and biochemical analysis were used to evaluate the effects of GE. H9C2 cells were used to verify the protective role of GE in vitro. GE treatment alleviated heart dysfunction and attenuated cardiac oxidative stress and cell loss induced by DOX in vivo and in vitro. GE could activate AMP-activated protein kinase α (AMPKα) in vivo and in vitro. Moreover, inhibition of AMPKα could abolish the protective effects of GE against DOX-induced oxidative stress and apoptosis. GE could protect against DOX-induced heart injury via activation of AMPKα. GE has therapeutic potential for the treatment of DOX cardiotoxicity.

Sign in / Sign up

Export Citation Format

Share Document