Evaluation of antigenotoxic effects of diosgenin in mice exposed to cyclophosphamide

2018 ◽  
Vol 9 (1) ◽  
pp. 96
Author(s):  
Hema G ◽  
Subbarao D ◽  
Thippeswamy BS
Keyword(s):  
Lipid Peroxidation ◽  
Reduced Glutathione ◽  
Steroidal Saponin ◽  
Dependent Manner ◽  
Chemotherapeutic Drugs ◽  
Immune Parameters ◽  
Wide Range ◽  
Dose Dependent ◽  
Antigenotoxic Effects ◽  
Wild Yam

Diosgenin is a steroidal saponin found in a variety of plants including fenugreek and roots of wild yam and is widely used in traditional medicine systems. Diosgenin is shown to have anti-invasive, anti-proliferative and proapoptotic activities on wide range of cancer cells and a well known precursor of various synthetic steroidal drugs that are extensively used in the pharmaceutical industry. The present investigation explores the genotoxic and antigenotoxic properties of diosgenin in experimental mice exposed to cyclophosphamide. CP increases the formation of micronucleated PCEs in the bone marrow of mice significantly and lowers the total WBC. In mice pre-treated with diosgenin, the formation of mnPCEs is lowered in a dose dependent manner and the immune parameters are restored. Diosgenin also reduces the lipid per oxidation levels indicated by MDA assessment and restores the antioxidant GSH in the liver tissues of the mice, counteracting the effects of CP. In our study, Diosgenin did not exhibit inherent genotoxic properties nor had a synergistic effect with CP. These results indicate the potential of diosgenin as an antigenotoxic agent with a possibility to be used as an adjuvant, to counteract the side-effects of chemotherapeutic drugs.  Keywords: Antigenotoxicity; Cyclophosphamide; Diosgenin; Micronucleated PCEs; WBC; Lipid peroxidation; Reduced glutathione

scholarly journals Preclinical Study on the Ameliorating Effect of L-Ascorbic Acid for the Oxidative Stress of Caused by Chronic Administration of Organic Nitrates in Cardiovascular Diseases

2021 ◽  
Author(s):  
Ahmed M Hamdan ◽  
Zuhair M. Mohammedsaleh ◽  
Aalaa Aboelnour ◽  
Sherif M.H. Elkhannishi
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Chronic Administration ◽  
Stress Factors ◽  
Male Rats ◽  
Oxidative Stress Marker ◽  
Organic Nitrates ◽  
Dependent Manner ◽  
Dose Dependent

Abstract PurposeThe therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. The principal objective of our research is to explain the ameliorating effect of L-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs. MethodsWe studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered ISMN. Afterwards, we evaluated the role of L-ascorbic acid against these biochemical changes. ResultsChronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in myocardium muscles in a dose dependent manner. Meanwhile, such exposure caused decline in the enzymatic effect of superoxide dismutase (SOD), glutathione (GSH) and catalase activity (CAT) accompanied with a decrease of in the level of mitochondrial oxidative stress marker (nrf2) in myocardium muscles and decrease in the serum iron and total iron binding capacity (TIBC) in a dose dependent manner. Concomitant treatment with L-ascorbic acid significantly diminished these changes for all examined parameters.ConclusionChronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to generation of reactive oxygen species. Using vitamin C can effectively ameliorate such intoxication to overcome the nitrate tolerance.

Oxidative stress biomarkers in the gills of the bivalve Mactra stultorum exposed to acrylamide

2020 ◽  
Vol 84 (2) ◽  
Author(s):  
Wafa Trabelsi ◽  
Chaima Fouzai ◽  
Imene Chetoui ◽  
Safa Bejaoui ◽  
Khaoula Telahigue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ache Activity ◽  
Reduced Glutathione ◽  
Lipid Hydroperoxides ◽  
Dependent Manner ◽  
Advanced Oxidation Protein Products ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
The Subject ◽  
Dose Dependent

Acrylamide (ACR) is among the most deleterious pollutants in the environment and presents a serious risk to humans and ecosystems. The purpose of this study was to assess its effects when administered at different concentrations (5, 10 and 20 mg L–1) to evaluate antioxidant status in the gills of Mactra stultorum. Our results showed, after five days of treat­ment, an increase in malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), reduced glutathione (GSH), ascorbic acid (Vit C) and metallothionein (MDA) levels in gills of treated clams compared with controls. Moreover, an increase in superoxide dismutase (SOD) and a significant decrease in glutathione peroxidase (GPx) activities were also observed. Acrylamide induced neurotoxicity, as evidenced by the inhibition of acetylcholinesterase (AChE) activity in a dose-dependent manner. Overall, our results indicated that oxidative stress may be considered one of the mechanisms behind acrylamide toxicity in bivalves, although the subject requires more research.

Protective Role of Raphanus Sativus Root Extract on Paracetamol-Induced Hepatotoxicity in Albino Rats

2007 ◽  
Vol 77 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Chaturvedi ◽  
George ◽  
Machacha
Keyword(s):  
Lipid Peroxidation ◽  
Raphanus Sativus ◽  
Thiobarbituric Acid ◽  
Protective Role ◽  
Albino Rats ◽  
Root Extract ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Serum Glutamate

The methanol extract of Raphanus sativus root extract showed a protective effect on paracetamol-induced hepatotoxicity in a dose-dependent manner. Degree of lipid peroxidation caused by paracetamol was measured in terms of thiobarbituric acid reactive substances (TBARS) and protection was measured in reference to serum glutamate oxaloacetate transaminase (SGOT), serum glutamate aspartate transaminase (SGPT), and blood and hepatic levels of antioxidants like glutathione and catalase. Administration of extract along with paracetamol showed significant protection. Levels of TBARS were found to be low, activities of SGOT and SGPT were low, while hepatic glutathione levels were significantly higher in experimental rats that received the mixture of paracetamol and the extract as compared to rats that received paracetamol only. Activities of catalase were also high in all experimental groups. Thus this study indicates the involvement of Raphanus sativus root extract with antioxidants like glutathione and catalase in rendering protection against paracetamol-induced lipid peroxidation and hepatotoxicity.

Protective Effect of Reduced Glutathione against CIS-Dichlorodiammine Platinum (II)–Induced Nephrotoxicity and Lethal Toxicity

1983 ◽  
Vol 69 (2) ◽  
pp. 105-111 ◽  
Author(s):  
Franco Zunino ◽  
Odoardo Tofanetti ◽  
Adriana Besati ◽  
Ennio Cavalletti ◽  
Giuseppina Savi
Keyword(s):  
Reduced Glutathione ◽  
Body Weight Loss ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Antitumor Effects ◽  
Partial Protection ◽  
Lethal Toxicity ◽  
Sprague Dawley Rats ◽  
Serum Blood Urea Nitrogen ◽  
Dose Dependent

Pretreatment of Swiss mice and Sprague-Dawley rats with glutathione (GSH) reduced the acute lethal toxicity of cis-dichlorodiammine platinum (II) (cis-DDP) in a dose-dependent manner. The protection was accompanied by reduction of both body weight loss and by reduction of nephrotoxicity, as measured by a rise in serum blood urea nitrogen (BUN), creatinine levels and by histopathologic changes, which occurred 4 days following cis-DDP treatment. The antitumor effects of cis-DDP on experimental tumor models (P388 and Gross leukemia) were not significantly altered by GSH treatment. It is suggested that the partial protection by GSH from acute toxicity of the antitumor drug is directly related to protection of renal function.

In vitro inhibition of phosphodiesterase-5 and arginase activities from rat penile tissue by two Nigerian herbs (Hunteria umbellata and Anogeissus leiocarpus)

2017 ◽  
Vol 28 (4) ◽  
Author(s):  
Ganiyu Oboh ◽  
Adeniyi Abiodun Adebayo ◽  
Ayokunle Olubode Ademosun ◽  
Aline August Boligon
Keyword(s):  
Lipid Peroxidation ◽  
Dependent Manner ◽  
Inhibitory Property ◽  
In Vitro Inhibition ◽  
Anogeissus Leiocarpus ◽  
Dose Dependent ◽  
Phosphodiesterase 5

AbstractBackground:andMethods:The effects of the extracts on important enzymes (PDE-5 and arginase) linked with ED and pro-oxidants (FeResults:The results showed that both extracts inhibited PDE-5 and arginase activities in a dose-dependent manner. Inhibitory property ofConclusions:The ability of the extracts to inhibit PDE-5, arginase and pro-oxidant induced lipid peroxidation, and chelate metal might suggest their folkloric use for the management of ED.

scholarly journals Calcium and calmodulin in the regulation of human thyroid adenylate cyclase activity

1985 ◽  
Vol 225 (3) ◽  
pp. 581-589 ◽  
Author(s):  
T Lakey ◽  
S Mac Neil ◽  
H Humphries ◽  
S W Walker ◽  
D S Munro ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Metal Ion ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Human Thyroid ◽  
Dependent Manner ◽  
Biphasic Response ◽  
Thyroid Stimulating Immunoglobulins ◽  
Wide Range ◽  
Dose Dependent

TSH (thyrotropin)-stimulated human thyroid adenylate cyclase has a biphasic response to Ca2+, being activated by submicromolar Ca2+ (optimum 22nM), with inhibition at higher concentrations. Calmodulin antagonists caused an inhibition of TSH-stimulated adenylate cyclase in a dose-dependent manner. Inhibition of TSH-and TSIg-(thyroid-stimulating immunoglobulins)-stimulated activity was more marked than that of basal, NaF- or forskolin-stimulated activity. This inhibition was not due to a decreased binding of TSH to its receptor. Addition of pure calmodulin to particulate preparations of human non-toxic goitre which had not been calmodulin-depleted had no effect on adenylate cyclase activity. EGTA was ineffective in removing calmodulin from particulate preparations, but treatment with the tervalent metal ion La3+ resulted in a loss of up to 98% of calmodulin activity from these preparations. Addition of La3+ directly to the adenylate cyclase assay resulted in a partial inhibition of TSH- and NaF-stimulated activity, with 50% inhibition produced by 5.1 microM and 4.0 microM-La3+ respectively. Particulate preparations with La3+ showed a decrease of TSH- and NaF-stimulated adenylate cyclase activity (approx. 40-60%). In La3+-treated preparations there was a decrease in sensitivity of TSH-stimulated adenylate cyclase to Ca2+ over a wide range of Ca2+ concentrations, but most markedly in the region of the optimal stimulatory Ca2+ concentration. In particulate preparations from which endogenous calmodulin had been removed by La3+ treatment, the addition of pure calmodulin caused an increase (73 +/- 22%; mean +/- S.E.M., n = 8) in TSH-stimulated thyroid adenylate cyclase activity. This was seen in 8 out of 13 experiments.

OxLDL Inhibits Brain Angiogenesis in Dose Dependent Manner via Reducing Level of VEGF and Angiopoietin-2: A Comprehensive Study

2017 ◽  
Author(s):  
Tasneem Alniqrish ◽  
Saed Khawaldeh
Keyword(s):  
Endothelial Cells ◽  
Human Brain ◽  
Angiogenic Factor ◽  
Microvascular Endothelial Cells ◽  
Dependent Manner ◽  
Brain Microvascular Endothelial Cells ◽  
Wide Range ◽  
Microvascular Endothelial ◽  
Dose Dependent ◽  
Brain Angiogenesis

Hyperlipidemia is recognized as a major health problem worldwide, moreover, it is considered as a major risk factor for cardiovascular and cerebrovascular diseases development. Since the majority of studies were performed to investigate the effect of hyperlipidemia on the angiogenesis of peripheral derived endothelial cell, this study aims to assess the effect of hyperlipidemia on the angiogenic response of human brain cells in a fast, easy and inexpensive method. Furthermore, it aims also to assess the involvement of Vascular Endothelial Growth Factor (VEGF) and angiopoietin. To achieve this aim, human Brain Microvascular Endothelial Cells (hBMECs) were treated with different concentration of Oxidized Low Density Lipoprotein (OxLDL) (1-100 μg/ml) for 24 hours. Migration rate and tube formation as markers of angiogenesis were performed, also Coomassie blue was used to detect protein level. OxLDL was found to inhibit brain angiogenesis in dose dependent manner over a wide range of concentrations (1-100 μg/ml). Using 1 μg/ml of OxLDL made minimum reduction of 10% whereas using 100 μg/ml of OxLDL resulted 70-80% reduction in the angiogenic potential of hBMECs within 24 hours. Moreover, OxLDL mediated its effect through reduced VEGF level and this effect was partially reversed by administered 5 ng/ml of VEGF. Additionally, OxLDL reduced the level of angiopoitin-2. This further supports the assumption that OxLDL has an anti-angiogenic effect in hBMECs and surely in the brain also. As a conclusion, OxLDL inhibits brain angiogenesis in dose dependent manner through reducing the level of angiogenic factor in human brain microvascular endothelial cells. We achieved our goal of having a preliminary indicator of brain angiogenesis under hyperlipidemia by using a simple but well-developed technique that incorporated the minimal number of tests and the cheapest.

scholarly journals Antioxidant, anti-inflammatory and anticoagulant activities of three Thymus species grown in southeastern Morocco

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Abdelbassat Hmidani ◽  
Eimad Dine Tariq Bouhlali ◽  
Tarik Khouya ◽  
Mhamed Ramchoun ◽  
Younes Filali-Zegzouti ◽  
...  
Keyword(s):  
Anticoagulant Activity ◽  
Activated Partial Thromboplastin Time ◽  
Dependent Manner ◽  
Thrombin Time ◽  
Thymus Zygis ◽  
Wide Range ◽  
Thymus Satureioides ◽  
Anti Inflammatory ◽  
Dose Dependent

Abstract Background Thyme has been used for centuries in southeastern Morocco to treat a wide range of diseases such as inflammation disorders. The aim of the current study is to examine and to compare in vitro the anti-inflammatory, antioxidant, and anticoagulant activities of three thyme species grown in southeastern Morocco. Results Data showed that all studied species possess an important antioxidant activity: Thymus atlanticus (IC50 = 16.59 μg/mL), Thymus zygis (IC50 = 15.43 μg/mL), and Thymus satureioides (IC50 = 14.65 μg/mL). Concerning the anti-inflammatory activity, the highest effect was depicted in Thymus atlanticus followed by Thymus zygis and Thymus satureioides. With regard to the anticoagulant activity, the aqueous extract of these species prolongs activated partial thromboplastin time, prothrombin time, and thrombin time significantly (p < 0.05) in a dose-dependent manner. Conclusion Our results provide evidence that thymus extract exhibits marked antioxidant, anticoagulant, and anti-inflammatory effects, thus justifying the popular uses of these plants to treat some inflammatory and cardiovascular illnesses.

scholarly journals Selection for Drug Resistance Results in Resistance to Fas-Mediated Apoptosis

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 1854-1861 ◽  
Author(s):  
Terry H. Landowski ◽  
Mary C. Gleason-Guzman ◽  
William S. Dalton
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Antigen Expression ◽  
Lymphoid Cells ◽  
Dependent Manner ◽  
Chemotherapeutic Drugs ◽  
Mechanisms Of Resistance ◽  
Fas Antigen ◽  
Selection For ◽  
Dose Dependent

Abstract Recent evidence has supported the hypothesis that chemotherapeutic drugs and radiation induce an apoptotic pathway that requires the active participation of the cell. One pathway of apoptosis in malignant lymphoid cells is mediated by the Fas antigen. We studied the human myeloma (8226) and T-cell leukemia (CEM) cell lines selected for resistance to the anthracenes, doxorubicin or mitoxantrone, by continuous culture in the presence of either agent. We found that these drug-resistant cell lines were also resistant to Fas-mediated apoptosis in a dose-dependent manner. The degree of resistance to Fas-mediated apoptosis correlated directly with the level of resistance to chemotherapeutic drugs. These observations indicate that, as cancer cell lines develop mechanisms of drug resistance, they may also develop mechanisms of resistance to physiologic signals of apoptosis. Two mechanisms of resistance to Fas-mediated apoptosis were observed in these cell lines. One mechanism was associated with a dose-dependent reduction in the surface expression of Fas antigen. Analysis of RNA by reverse transcriptase-polymerase chain reaction assays showed that the reduction of Fas antigen expression occurred at the level of transcription. A second mechanism of drug resistance showed no decrease of Fas antigen expression; however, the apoptotic response was diminished. In this situation, removal of the chemotherapeutic agent resulted in a partial reversion to chemosensitivity and re-expression of the Fas antigen, but these cell lines did not regain the ability to undergo apoptosis in response to cross-linking by anti-Fas antibody. These findings support the hypothesis that apoptosis mediated by both chemotherapeutic agents and physiologic stimuli may share a common downstream effector. The demonstration that selection for drug resistance in hematopoietic cell lines results in a simultaneous resistance to Fas-mediated apoptosis may have clinical implications in the development of strategies for the treatment of resistant disease. Further analysis of the molecular mechanisms of Fas expression and function will facilitate the design of biological response modifying agents for the treatment of malignancy.

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