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Drug induced mitochondrial toxicity

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https://www.readbyqxmd.com/read/29762537/the-cardioprotective-effect-of-metformin-in-doxorubicin-induced-cardiotoxicity-the-role-of-autophagy
#1
Rita Zilinyi, Attila Czompa, Andras Czegledi, Andrea Gajtko, Dora Pituk, Istvan Lekli, Arpad Tosaki
The molecular mechanisms underlying doxorubicin-induced cardiotoxicity are still being investigated, but are known to involve oxidative stress, mitochondrial dysfunction, and the dysregulation of autophagy. The objective of the current study was to examine the protective role of metformin and its effect on autophagy in doxorubicin-induced cardiotoxicity. Sprague⁻Dawley rats were divided into four groups at random. The doxorubicin-treated group received doxorubicin (3 mg/kg every second day) intraperitoneally...
May 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29762467/inhibition-of-proliferation-in-u937-cells-treated-by-blue-light-irradiation-and-combined-blue-light-irradiation-drug
#2
Jianjian Zhuang, Junsong Liu, Xuan Gao, Hongdong Li
The cell viability and apoptosis of tumor U937 cells treated by blue light (BL) irradiation have been examined. BL irradiation can specially inhibit the proliferation and promote the apoptosis of U937 cells, relating to the production of reactive oxygen species (ROS) and the decline of mitochondrial membrane potential (ΔΨm). The apoptosis is further associated with varying downregulated B-cell lymphoma-extra large ( Bcl-XL ) and B-cell lymphoma 2 ( Bcl-2 ) genes, upregulated Bcl-2-associated X ( Bax ) gene, the activation of caspase-3 and caspase-9, and the cleavage of poly (ADP-ribose) polymerase (PARP) by the BL irradiation process...
May 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29761845/the-o-methylated-isoflavone-formononetin-inhibits-human-ovarian-cancer-cell-proliferation-by-sub-g0-g1-cell-phase-arrest-through-pi3k-akt-and-erk1-2-inactivation
#3
Sunwoo Park, Fuller W Bazer, Whasun Lim, Gwonhwa Song
Formononetin is an isoflavone that is extracted from red clovers or soy. It has anti-oxidant, anti-proliferative, and anti-tumor effects against cells in various diseases. Several cohort studies have indicated that phytoestrogen intake, including formononetin, could reduce the risk of various carcinogenesis. In fact, many case-control studies have indicated the potential value of flavonoids as drug supplements in the treatment of many cancer patients. However, the toxic effects and the anti-cancer mechanism of formononetin in ovarian cancer are unknown...
May 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29761207/omics-based-responses-induced-by-bosentan-in-human-hepatoma-heparg-cell-cultures
#4
Robim M Rodrigues, Laxmikanth Kollipara, Umesh Chaudhari, Agapios Sachinidis, René P Zahedi, Albert Sickmann, Annette Kopp-Schneider, Xiaoqi Jiang, Hector Keun, Jan Hengstler, Marlies Oorts, Pieter Annaert, Eef Hoeben, Eva Gijbels, Joery De Kock, Tamara Vanhaecke, Vera Rogiers, Mathieu Vinken
Bosentan is well known to induce cholestatic liver toxicity in humans. The present study was set up to characterize the hepatotoxic effects of this drug at the transcriptomic, proteomic, and metabolomic levels. For this purpose, human hepatoma-derived HepaRG cells were exposed to a number of concentrations of bosentan during different periods of time. Bosentan was found to functionally and transcriptionally suppress the bile salt export pump as well as to alter bile acid levels. Pathway analysis of both transcriptomics and proteomics data identified cholestasis as a major toxicological event...
May 14, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29753871/combinatorial-usage-of-fungal-polysaccharides-from-cordyceps-sinensis-and-ganoderma-atrum-ameliorate-drug-induced-liver-injury-in-mice
#5
Songtao Fan, Xiaojun Huang, Sunan Wang, Chang Li, Zhihong Zhang, Mingyong Xie, Shaoping Nie
This study investigated the possible protective effect of combined fungal polysaccharides (CFP), consisting of Cordyceps sinensis polysaccharides (CSP) and Ganoderma atrum polysaccharides (PSG) with well-defined structural characteristics, against cyclophosphamide (CTX)-induced hepatotoxicity in mice. Our results indicated CFP effectively prevented the liver injury by decreasing toxicity markers (aspartate transaminase, alanine aminotransferase and alkaline phosphatase). Further biochemical and molecular analysis indicated CSP particularly inhibited the activation of Toll-like receptor 9 (TLR9) and its related inflammatory signals, including pro-inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 to modulate hepatic inflammation response...
May 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29751151/different-administration-patterns-of-docosahexaenoic-acid-in-combating-cytotoxic-manifestations-due-to-arsenic-trioxide-acute-promyelocytic-leukemia-drug-induced-redox-imbalance-in-hepatocytes
#6
S Abhilash, R Siviyasankar, P Binu, P Arathi, R Harikumaran Nair
Docosahexaenoic acid (DHA) obtained from fish and plant sources is an essential dietary fatty acid and an important cell membrane structural component. The acute promyelocytic leukemia (APL) drug arsenic trioxide (As2 O3 ), causes hepatotoxicity. We evaluated the protective potential of DHA as pre/ combination/ post-administration patterns against As2 O3 induced toxicity. The therapeutic concentration of As2 O3 (10 µM) resulted in cytotoxicity with a significant (p < 0.05) variation from the control group...
May 8, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29743983/chemotherapeutic-drugs-and-mitochondrial-dysfunction-focus-on-doxorubicin-trastuzumab-and-sunitinib
#7
REVIEW
Stefania Gorini, Antonella De Angelis, Liberato Berrino, Natalia Malara, Giuseppe Rosano, Elisabetta Ferraro
Many cancer therapies produce toxic side effects whose molecular mechanisms await full elucidation. The most feared and studied side effect of chemotherapeutic drugs is cardiotoxicity. Also, skeletal muscle physiology impairment has been recorded after many chemotherapeutical treatments. However, only doxorubicin has been extensively studied for its side effects on skeletal muscle. Chemotherapeutic-induced adverse side effects are, in many cases, mediated by mitochondrial damage. In particular, trastuzumab and sunitinib toxicity is mainly associated with mitochondria impairment and is mostly reversible...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29743445/increased-susceptibility-to-troglitazone-induced-mitochondrial-permeability-transition-in-type-2-diabetes-mellitus-model-rat
#8
Masahiro Segawa, Shuichi Sekine, Tomoyuki Sato, Kousei Ito
Troglitazone, a member of the thiazolidinedione class of antidiabetic drugs, was withdrawn from the market because it causes severe liver injury. One of the mechanisms for this adverse effect is thought to be mitochondrial toxicity. To investigate the characteristics of troglitazone-induced liver toxicity in more depth, the toxicological effects of troglitazone on hepatocytes and liver mitochondria were investigated using a rat model of type 2 diabetes mellitus (T2DM). Troglitazone was found to increase mitochondrial permeability transition (MPT) in the liver mitochondria of diabetic rats to a greater extent than in control rats, whereas mitochondrial membrane potential and oxidative phosphorylation were not affected...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29742069/a-simple-robust-method-of-synthesis-of-copper-silver-core-shell-nano-particle-evaluation-of-its-structural-and-chemical-properties-with-anticancer-potency
#9
Milon Banik, Mousumi Patra, Debanjan Dutta, Riya Mukherjee, Tarakdas Basu
A simple method of synthesis of stable bimetallic copper-silver nanoparticle (Cu@Ag NP) was developed by successive reduction of Cu(NO3)2 and AgNO3, using hydrazine hydrate as the reducing agent and gelatine and Poly-vinyl pyrrolidone (PVP) as the capping agents. The round-shaped particles were of core-shell structure with a core of Cu0 atoms surrounded by a shell of Ag0 atoms. The size and the mol. wt. of the NPs were (100 ± 10) nm and (820 ± 157) Kd respectively; the particles were crystalline in nature and 90% of the precursors Cu(NO3)2 and AgNO3 were converted to the NPs...
May 9, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29734752/mitoxantrone-is-more-toxic-than-doxorubicin-in-sh-sy5y-human-cells-a-chemobrain-in-vitro-study
#10
Daniela Almeida, Rita Pinho, Verónica Correia, Jorge Soares, Maria de Lourdes Bastos, Félix Carvalho, João Paulo Capela, Vera Marisa Costa
The potential neurotoxic effects of anticancer drugs, like doxorubicin (DOX) and mitoxantrone (MTX; also used in multiple sclerosis), are presently important reasons for concern, following epidemiological data indicating that cancer survivors submitted to chemotherapy may suffer cognitive deficits. We evaluated the in vitro neurotoxicity of two commonly used chemotherapeutic drugs, DOX and MTX, and study their underlying mechanisms in the SH-SY5Y human neuronal cell model. Undifferentiated human SH-SY5Y cells were exposed to DOX or MTX (0...
May 5, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29731891/synergistic-effects-of-cisplatin-caffeic-acid-induces-apoptosis-in-human-cervical-cancer-cells-via-the-mitochondrial-pathways
#11
Amonrat Koraneekit, Temduang Limpaiboon, Arunnee Sangka, Patcharee Boonsiri, Sakda Daduang, Jureerut Daduang
Cervical cancer (CxCa) is a major health problem globally and is associated with the presence of human papillomavirus infection. Cisplatin (CDDP) is a platinum-based chemotherapeutic agent. Owing to its side effects and drug-resistance, novel anticancer agents with lower toxicity, including caffeic acid (CFC), are of interest. However, the effects of CDDP and CFC in combination are, to the best of our knowledge, uninvestigated. The present study investigated the effectiveness of CDDP and CFC in combination and its mechanism of action on four human cervical cancer cell lines, which were compared with the Chlorocebus sabaeus normal kidney Vero cell line...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29730133/cytotoxic-effect-of-kalanchoe-flammea-and-induction-of-intrinsic-mitochondrial-apoptotic-signaling-in-prostate-cancer-cells
#12
Iván Arias-González, Alejandro M García-Carrancá, Jorge Cornejo-Garrido, Cynthia Ordaz-Pichardo
Ethnopharmacological importance: Kalanchoe flammea Stapf (Crassulaceae) is a medicinal plant grown in the South of Mexico (State of Tabasco), which is commonly used in traditional medicine for the treatment of fever, wounds, inflammation, and cancer. AIM OF THE STUDY: To establish the potential of K. flammea for the treatment of prostate cancer, evaluating its cytotoxic activity, its probable mechanism of action, and carrying out some toxicological safety studies. MATERIALS AND METHODS: The cytotoxic activity of the ethyl acetate extract of K...
May 3, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29729261/zoledronic-acid-induces-micronuclei-formation-mitochondrial-mediated-apoptosis-and-cytostasis-in-kidney-cells
#13
Soma Shiva Nageswara Rao Singireesu, Sujan Kumar Mondal, Suresh Yerramsetty, Sunil Misra
AIMS: Zoledronic acid (ZA), a FDA approved drug has used widely in the treatment of bone metastasis complications, has been linked to renal toxicity with unclear mechanism. The present study is aimed at investigating genotoxic and cytotoxic effects of ZA in renal epithelial cells. MAIN METHODS: The genotoxic effect of ZA in Vero and MDCK cells determined by cytokinesis block micronucleus (CBMN) assay. The cytotoxic effect assessed by analysing cell cycle profile, cell death and mitochondrial membrane potential by flow cytometry using propidium iodide, AnnexinV-FITC/PI and JC1 dye staining, respectively, BAX and Bcl-2 expression by Western blotting and caspase activity by spectrofluorimetry...
May 2, 2018: Life Sciences
https://www.readbyqxmd.com/read/29726253/multifunctional-glycoconjugate-assisted-nanocrystalline-drug-delivery-for-tumor-targeting-and-permeabilization-of-lysosomal-mitochondrial-membrane
#14
Gitu Pandey, Naresh Mittapelly, Venkatesh Teja Banala, Prabhat Ranjan Mishra
Nanotechnology has emerged as the most successful strategy for targeting the drug payloads to the tumors with potential to overcome the problems of low concentration at the target site, nonspecific distribution and untoward toxicities. Here, we synthesized a novel polymeric conjugate comprising of chondroitin sulfate A and polyethylene glycol using carbodiimide chemistry. We further employed this glycoconjugate possessing the propensity to provide stability, stealth effect and tumor targeting via CD44 receptors, all in one, to develop a nanocrystalline system of docetaxel (DTX@CSA-NCs) with size< 200nm, negative zeta potential and 98% drug content...
May 4, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29719618/onc201-kills-breast-cancer-cells-in-vitro-by-targeting-mitochondria
#15
Yoshimi Endo Greer, Natalie Porat-Shliom, Kunio Nagashima, Christina Stuelten, Dan Crooks, Vishal N Koparde, Samuel F Gilbert, Celia Islam, Ashley Ubaldini, Yun Ji, Luca Gattinoni, Ferri Soheilian, Xiantao Wang, Markus Hafner, Jyoti Shetty, Bao Tran, Parthav Jailwala, Maggie Cam, Martin Lang, Donna Voeller, William C Reinhold, Vinodh Rajapakse, Yves Pommier, Roberto Weigert, W Marston Linehan, Stanley Lipkowitz
We report a novel mechanism of action of ONC201 as a mitochondria-targeting drug in cancer cells. ONC201 was originally identified as a small molecule that induces transcription of TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cancer cells by activating TRAIL death receptors. In this study, we examined ONC201 toxicity on multiple human breast and endometrial cancer cell lines. ONC201 attenuated cell viability in all cancer cell lines tested. Unexpectedly, ONC201 toxicity was not dependent on either TRAIL receptors nor caspases...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719092/evaluation-of-the-toxicity-effects-of-silk-fibroin-on-human-lymphocytes-and-monocytes
#16
Parvaneh Naserzadeh, Seyed Alireza Mortazavi, Khadijeh Ashtari, Ahmad Salimi, Mehdi Farokhi, Jalal Pourahmad
Silk fibroin nanoparticles (SFNPs) as a natural polymer have been utilized in biomedical applications such as suture, tissue engineering-based scaffolds, and drug delivery carriers. Since there is little data regarding the toxicity effects on different cells and tissues, we aimed to determine the toxicity mechanisms of SFNPs on human lymphocytes and monocytes based on reliable methods. Our results showed that SFNPs (0.5, 1, and 2 mg/mL) induced oxidative stress via increasing reactive oxygen species production, mitochondrial membrane potential (∆Ψ) collapse, which was correlated to cytochrome c release and Adenosine diphosphate (ADP)/Adenosine tri phosphate (ATP) ratio increase as well as lysosomal as another toxicity mechanism, which led to cytosolic release of lysosomal digestive proteases, phosphor lipases, and apoptosis signaling...
May 2, 2018: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29715466/feraheme%C3%A2-suppresses-immune-function-of-human-t-lymphocytes-through-mitochondrial-damage-and-mitoros-production
#17
Ankit Shah, Cassandra I Mankus, Alison M Vermilya, Ferri Soheilian, Jeffrey D Clogston, Marina A Dobrovolskaia
Despite attractive properties for both therapeutic and diagnostic applications, the clinical use of iron oxide nanoparticles (IONPs) is limited to iron replacement in severely anemic patient populations. While several studies have reported about the immunotoxicity of IONPs, the mechanisms of this toxicity are mostly unknown. We conducted a mechanistic investigation using an injectable form of IONP, Feraheme®. In the cultures of primary human T cells, Feraheme induced miotochondrial oxidative stress and resulted in changes in mitochondrial dynamics, architecture, and membrane potential...
April 28, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29704481/grewia-tiliaefolia-and-its-active-compound-vitexin-regulate-the-expression-of-glutamate-transporters-and-protect-neuro2a-cells-from-glutamate-toxicity
#18
Dicson Sheeja Malar, Mani Iyer Prasanth, Rajamohamed Beema Shafreen, Krishnaswamy Balamurugan, Kasi Pandima Devi
AIM: Glutamate is a major neurotransmitter involved in several brain functions and glutamate excitotoxicity is involved in Alzheimer's disease (AD). In the current study, the neuroprotective effect of the Indian medicinal plant Grewia tiliaefolia (GT) and its active component vitexin was evaluated in Neuro-2a cells against glutamate toxicity. MATERIALS AND METHODS: Neuro-2a cells were exposed to glutamate to cause excitotoxicity and the neuroprotective effect of GT and vitexin were evaluated using biochemical studies (estimation of reactive oxygen species, reactive nitrogen species, protein carbonyl content, lipid peroxidation level, mitochondrial membrane potential and caspase-3 activity), molecular docking studies, gene expression and western blot analysis...
April 25, 2018: Life Sciences
https://www.readbyqxmd.com/read/29701781/mutant-app-and-amyloid-beta-induced-defective-autophagy-mitophagy-mitochondrial-structural-and-functional-changes-and-synaptic-damage-in-hippocampal-neurons-from-alzheimer-s-disease
#19
P Hemachandra Reddy, XiangLin Yin, Maria Manczak, Subodh Kumar, Pradeepkiran Jangampalli Adi, Murali Vijayan, Arubala P Reddy
The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in human mutant APP (mAPP) cDNA transfected with primary mouse hippocampal neurons (HT22). Hippocampal tissues are the best source of studying learning and memory functions in patients with Alzheimer's disease (AD) and healthy controls. However, investigating immortalized hippocampal neurons that express AD proteins provide an excellent opportunity for drug testing. Using quantitative RT-PCR, immunoblotting & immunofluorescence, and transmission electron microscopy, we assessed mRNA and protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2, and assessed mitochondrial number and length in mAPP-HT22 cells that express Swedish/Indiana mutations...
April 25, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29686775/beneficial-effects-of-cynaroside-on-cisplatin-induced-kidney-injury-in-vitro-and-in-vivo
#20
Jong-Hyun Nho, Ho-Kyung Jung, Mu-Jin Lee, Ji-Hun Jang, Mi-Ok Sim, Da-Eun Jeong, Hyun-Woo Cho, Jong-Choon Kim
Anti-cancer drugs such as cisplatin and doxorubicin are effectively used more than radiotherapy. Cisplatin is a chemotherapeutic drug, used for treatment of various forms of cancer. However, it has side effects such as ototoxicity and nephrotoxicity. Cisplatin-induced nephrotoxicity increases tubular damage and renal dysfunction. Consequently, we investigated the beneficial effect of cynaroside on cisplatin-induced kidney injury using HK-2 cell (human proximal tubule cell line) and an animal model. Results indicated that 10 μM cynaroside diminished cisplatin-induced apoptosis, mitochondrial dysfunction and caspase-3 activation, cisplatin-induced upregulation of caspase-3/MST-1 pathway decreased by treatment of cynaroside in HK-2 cells...
April 2018: Toxicological Research
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