scholarly journals Toxicity and Loss of Mitochondrial Membrane Potential Induced by Alkyl Gallates in Trypanosoma cruzi

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Rogério Andréo ◽  
Luís Octávio Regasini ◽  
Maicon Segalla Petrônio ◽  
Bruna Galdorfini Chiari-Andréo ◽  
Aline Tansini ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mechanism Of Action ◽  
Social Problem ◽  
Mitochondrial Membrane ◽  
Side Chain ◽  
Synergistic Activity ◽  
Alkyl Gallates ◽  
Structure Activity ◽  
The World

American trypanosomiasis or Chagas disease is a debilitating disease representing an important social problem that affects, approximately, 10 million people in the world. The main aggravating factor of this situation is the lack of an effective drug to treat the different stages of this disease. In this context, the search for trypanocidal substances isolated from plants, synthetic or semi synthetic molecules, is an important strategy. Here, the trypanocidal potential of gallates was assayed in epimastigotes forms of T. cruzi and also, the interference of these substances on the mitochondrial membrane potential of the parasites was assessed, allowing the study of the mechanism of action of the gallates in the T. cruzi organisms. Regarding the preliminary structure-activity relationships, the side chain length of gallates plays crucial role for activity. Nonyl, decyl, undecyl, and dodecyl gallates showed potent antitrypanosomal effect (IC50 from 1.46 to 2.90 μM) in contrast with benznidazole (IC50 = 34.0 μM). Heptyl gallate showed a strong synergistic activity with benznidazole, reducing by 105-fold the IC50 of benznidazole. Loss of mitochondrial membrane potential induced by these esters was revealed. Tetradecyl gallate induced a loss of 53% of the mitochondrial membrane potential, at IC50 value.

scholarly journals The effect of acrylamide on mitochondrial membrane potential and glutathione extraction in human spermatozoa: A laboratory study

2020 ◽  
Author(s):  
Zeinab Omidi ◽  
Zeinab Piravar ◽  
Mina Ramezani
Keyword(s):  
Membrane Potential ◽  
World Health Organization ◽  
Mitochondrial Membrane Potential ◽  
Laboratory Study ◽  
Mitochondrial Membrane ◽  
Human Sperm ◽  
World Health ◽  
The World ◽  
Intracellular Glutathione ◽  
Health Organization

Background: Acrylamide (AA) is a compound used in the industrial production of polyacrylamide. AAs affects by creating oxidative stress. It produces reactive oxygen species and leads to lipid peroxide. Lipid peroxidation in the cell membrane is one of the most important oxidations in the sperm, which can disrupt the fluidity and permeability of cell membranes and damage all cells. Objective: To investigate the different concentrations of AA on human sperm parameters based on the World Health Organization standard and its impact on mitochondrial membrane potential and sperm glutathione levels. Materials and Methods: In this laboratory study, we examined the different concentrations of AA on human sperm parameters based on the World Health Organization standard and its impact on mitochondrial membrane potential by flow cytometry and sperm glutathione levels by ELISA assay. Results: The results were reported as the mean fluorescence intensity of JC and the index was observed to decrease following the effect of AA in mitochondrial membrane potential (Δ Ψm). The results of ELISA test to study the level of intracellular glutathione showed that with the increase in the concentration of AA exposed to sperms, there was a significant reduction in the level of intracellular glutathione. Conclusion: AA destroys the sperm membrane integrity under apoptotic and oxidative inductions with a negative impact on mitochondrial function and antioxidative enzyme in sperm such as glutathione. Key words: Acrylamides, Spermatozoa, Mitochondrial membrane potential, Glutathione S-Transferase.

Flavopiridol Decreases Mcl-1 and Initiates Early Mitochondrial Damage in Chronic Lymphocytic Leukemia (CLL) Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2098-2098
Author(s):  
David M. Lucas ◽  
Syed-Rehan A. Hussain ◽  
Amy J. Johnson ◽  
Lisa L. Smith ◽  
Amy J. Wagner ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mechanism Of Action ◽  
Mitochondrial Membrane ◽  
Tumor Lysis Syndrome ◽  
Annexin V ◽  
Caspase 8 ◽  
Adapter Protein ◽  
Tumor Lysis

Abstract We have noted impressive activity of the cyclin-dependent kinase inhibitor flavopiridol in advanced-stage CLL patients, including those with a deletion of chromosome 17p13. Using a novel, effective schedule of flavopiridol, substantial and sometimes dramatic evidence of tumor cell death is observed as early as 4–6 hours. This is accompanied by hyperkalemia, hyperphosphatemia, hypocalcemia, and dramatic elevation in LDH consistent with acute tumor lysis syndrome. Studies by several groups including our own have demonstrated that Mcl-1 protein and mRNA is down-regulated with flavopiridol. Mcl-1 is an important protein that contributes to mitochondrial membrane stability. We have therefore sought to determine the role of mitochondria disruption in the mechanism of action of flavopiridol. By flow cytometry using the voltage-sensitive dye JC-1, loss of mitochondrial membrane potential was detected in flavopiridol-treated whole blood as early as five hours, prior to the onset of annexin-V or propidium iodide staining. This is in contrast to in vitro studies using human serum, in which mitochondrial depolarization and annexin-V staining occurred simultaneously. In isolated CLL cells treated with flavopiridol in vitro, loss of mitochondrial membrane potential was not affected by inhibitors of caspases 8 or 9 or by the broad caspase inhibitor Z-VAD-fmk, although apoptosis was effectively blocked by Z-VAD-fmk and caspase-8 inhibitor, and to a lesser extent, caspase-9 inhibitor. Flavopiridol was also able to effectively induce apoptosis and mitochondrial membrane depolarization in Jurkat cell lines deficient in caspase-8 or its adapter protein FADD. Additionally, lymphoid cells overexpressing Bcl-2 are resistant to flavopiridol-mediated apoptosis relative to the vector control. This suggests there is not direct binding of flavopiridol or its metabolites to APAF-1 (cytosolic adapter protein) and apoptosome assembly, as this process is insensitive to Bcl-2 family proteins. Further mechanistic studies were undertaken using isolated liver mitochondria. While the electron transport system was not uncoupled in this system, potential mechanisms of mitochondrial injury in leukemic cells from CLL patients are currently under exploration. Taken together, these observations suggest that mitochondrial perturbation contributes significantly to the death process induced by flavopiridol. Further studies to identify the mechanism of mitochondrial perturbation will be essential to understanding flavopiridol’s mechanism of action and for predicting patients at risk for acute tumor lysis syndrome. (Support for this work was provided by the Samuel Waxman Foundation and the Leukemia & Lymphoma Society.)

scholarly journals Mechanism of action of levocarnitine for the treatment of spermatogenic dysfunction in rats and spermatogonia

2021 ◽  
Author(s):  
Jisheng Wang ◽  
Binghao Bao ◽  
Fanchao Meng ◽  
Sheng Deng ◽  
Hengheng Dai ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mechanism Of Action ◽  
Mitochondrial Membrane ◽  
Cell Model ◽  
Sperm Count ◽  
Serum Levels ◽  
Underlying Mechanism ◽  
Pi3k Pathway ◽  
A Cell

Abstract The mechanism of action of levocarnitine (LEV) in the treatment of spermatogenic dysfunction was unclear. We used GTW to construct a cell model (using spermatogenic GC-1 spg cells) and an animal model (using rats) of spermatogenic dysfunction. LEV and LY294002 (a PI3K pathway inhibitor) were then administered. By assessing proliferation, mitochondrial membrane potential, apoptosis, and sex hormone levels, the underlying mechanism was explored. We found that (I) by regulating PI3K/AKT pathway-related protein expression, LEV increased the percentages of GC-1 spg cells in the G0/G1 and G2/M phases, increased the mitochondrial membrane potential, and decreased apoptosis, thereby improving the sperm count and motility and (II) LEV and significantly increased the T, FSH, and LH serum levels, thereby improving the spermatogenic function of rats.

Platelets apoptosis in rats after global brain ischemia

2018 ◽  
pp. 27-35
Author(s):  
А.А. Соколовская ◽  
Э.Д. Вирюс ◽  
В.В. Александрин ◽  
А.С. Роткина ◽  
К.А. Никифорова ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Ischemic Stroke ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Brain Ischemia ◽  
Mitochondrial Membrane ◽  
Male Rats ◽  
Global Brain Ischemia ◽  
Platelet Apoptosis ◽  
Global Brain

Цель исследования. Ишемические повреждения головного мозга, являются одной из наиболее частой причин инвалидности и смертности во всем мире. Недавно была установлена роль апоптоза тромбоцитов в патофизиологии инсульта, однако его механизмы до сих пор остаются невыясненными. Несмотря на различные экспериментальные модели, направленные на мониторинг апоптоза тромбоцитов, результаты, относительно изучения и выявления апоптоза тромбоцитов при ишемии головного мозга у крыс, весьма немногочисленны. Цель исследования - анализ апоптоза тромбоцитов с помощью метода проточной цитофлуориметрии на модели глобальной ишемии мозга у крыс. Методика. В экспериментах использовано 6 крыс-самцов Вистар в возрасте от 5 до 6 мес., разделенных на 2 группы: интактный контроль (К) и глобальная ишемия головного мозга. Модель глобальной ишемии головного мозга у крыс воспроизводилась путём билатеральной окклюзии общих сонных артерий на фоне гипотензии. Уровень системного артериального давления снижали посредством кровопотери до 40-45 мм рт. ст. Суспензию тромбоцитов крыс получали методом гельфильтрации с использованием сефарозы 2B. Для анализа экстернализации фосфатидилсерина (ФС) тромбоциты крыс инкубировали с Аннексином V-PE в связывающем буфере. Для оценки митохондриального мембранного потенциала (ММП) тромбоциты инкубировали с катионным красителем JC-1. После инкубации образцы немедленно анализировали на проточном цитофлуориметре FACSCalibur (Becton Dickinson, США). Результаты. Согласно полученным данным, экстернализация ФС на тромбоцитах крыс, перенесших инсульт, была значительно выше (53,45 ± 4,21%), чем в контрольной группе крыс (5,27 ± 2,40%). Данный эффект подтверждается выраженной деполяризацией митохондриальных мембран (DYm). После экспериментальной ишемии мозга почти 40% тромбоцитов было деполяризовано. Заключение. Использованный в работе подбор методов и маркеров обеспечивает понимание механизмов апоптоза тромбоцитов как в экспериментальных, так и в клинических условиях. Полученные данные позволяют сделать заключение, что апоптоз тромбоцитов является одним из факторов развития глобальной ишемии головного мозга у крыс. Результаты могут быть использованы для понимания механизмов, участвующих в развитии ишемического повреждения, что, в свою очередь, может быть использовано при разработке новых терапевтических стратегий. Aim. Stroke is one of the most common causes of disability and mortality worldwide. Multiple experimental models of stroke have focused on monitoring of platelet apoptosis. However, studies on and detection of platelet apoptosis in rats with ischemic stroke are very scarce. We investigated platelet apoptosis in rats with global brain ischemia using flow cytometry. Methods. Experiments were carried out on healthy, adult Wistar male rats weighing 300-350 g. The rats were divided into the following 2 groups: intact rats and rats with global brain ischemia. Global brain ischemia was induced by two-vessel (2-VO) carotid occlusion in combination with hypotension. Systemic blood pressure was reduced by 40-45 mm Hg by inducing haemorrhage. Platelets were isolated by gel filtration on Sepharose 2B. For evaluation of phosphatidylserine (PS) externalization, platelets were incubated with Annexin V-PE and analyzed on FACSCalibur (BD Biosciences). Mitochondrial membrane potential (DY) was measured during platelets apoptosis using JC-1, a mitochondrial membrane potential indicator. Platelets were analyzed by flow cytometry immediately after the incubation. Results. PS externalization on platelets was significantly greater after global brain ischemia (53.45 ± 4.21%) than in the control group (5.27 ± 2.40%). Pronounced depolarization of mitochondrial membrane potential (DYm) confirmed this finding. In the rat group with experimental brain ischemia, almost 40% (35.24 ± 5.21%) of platelets were depolarized. Conclusion. Our results provide insight into mechanisms involved in platelet apoptosis during ischemic stroke and can be used in further development of new therapeutic strategies.

Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

2019 ◽  
Vol 18 (9) ◽  
pp. 1313-1322 ◽  
Author(s):  
Manjula Devi Ramamoorthy ◽  
Ashok Kumar ◽  
Mahesh Ayyavu ◽  
Kannan Narayanan Dhiraviam
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

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