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Drug induced mitochondrial toxicity

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https://www.readbyqxmd.com/read/28338625/-r-aloesaponol-iii-8-methyl-ether-from-eremurus-persicus-a-novel-compound-against-leishmaniosis
#1
Daniela Rossi, Karzan Mahmood Ahmed, Raffaella Gaggeri, Serena Della Volpe, Lauretta Maggi, Giuseppe Mazzeo, Giovanna Longhi, Sergio Abbate, Federica Corana, Emanuela Martino, Marisa Machado, Raquel Varandas, Maria do Céu Sousa, Simona Collina
Leishmaniosis is a neglected tropical disease which affects several millions of people worldwide. The current drug therapies are expensive and often lack efficacy, mainly due to the development of parasite resistance. Hence, there is an urgent need for new drugs effective against Leishmania infections. As a part of our ongoing study on the phytochemical characterization and biological investigation of plants used in the traditional medicine of western and central Asia, in the present study, we focused on Eremurus persicus root extract in order to evaluate its potential in the treatment of leishmaniosis...
March 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28338413/human-tissue-engineered-skeletal-muscle-myobundles-to-measure-oxygen-uptake-and-assess-mitochondrial-toxicity
#2
Brittany N J Davis, Jeffrey W Santoso, Michaela J Walker, Cindy S Cheng, Timothy R Koves, William E Kraus, George A Truskey
Mitochondrial dysfunction is responsible for the toxicity of a number of drugs. Current isolated mitochondria or cellular monoculture mitochondrial respiration measurement systems lack physiological relevance. Using a tissue engineering rather than cell- or mitochondria-based approach enables a more physiologically relevant detection of drug-induced mitochondrial impairment. To probe oxygen consumption and mitochondrial health, we assayed the bioenergetic profile of engineered three-dimensional human skeletal muscle myobundles derived from primary myoblasts...
March 24, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28336091/altered-cellular-metabolism-of-hepg2-cells-caused-by-microcystin-lr
#3
Junguo Ma, Yiyi Feng, Siyu Jiang, Xiaoyu Li
This study aimed to evaluate the possible effects of microcystin-LR (MC-LR) exposure on the metabolism and drug resistance of human hepatocellular carcinoma (HepG2) cells. For this purpose, we first conducted an experiment to make sure that MC-LR could penetrate the HepG2 cell membrane effectively. The transcriptional levels of phase I (such as CYP2E1, CYP3A4, and CYP26B1) and phase II (such as EPHX1, SULTs, and GSTM) enzymes and export pump genes (such as MRP1 and MDR1) were altered by MC-LR-exposure for 24 h, indicating that MC-LR treatment may destabilize the metabolism of HepG2 cells...
March 21, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28329820/hepatocellular-toxicity-of-imidazole-and-triazole-antimycotic-agents
#4
Patrizia Haegler, Lorenz Joerin, Stephan Krähenbühl, Jamal Bouitbir
Hepatotoxicity has been described for all antimycotic azoles currently marketed. A possible mechanism involving mitochondrial dysfunction has been postulated for ketoconazole, but not for the other azoles. The aim of the current investigations was to study the toxicity of different azoles in human cell models and to find out mechanisms of their toxicity. In HepG2 cells, posaconazole and ketoconazole were cytotoxic starting at 20 and 50 µM and decreased the cellular ATP content starting at 5 and 10 µM, respectively...
January 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28322891/effect-of-antipsychotics-on-mitochondrial-bioenergetics-of-rat-ovarian-theca-cells
#5
Ekramy Elmorsy, Ayat Al-Ghafari, Amal Misbah Aggour, Soaad Mohamed Mosad, Raheela Khan, Saad Amer
BACKGROUND: Antipsychotics (APs) are widely prescribed drugs, which are well known to cause reproductive adverse effects through mechanisms yet to be determined. The purpose of this study was to investigate the effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells as a possible mechanism of reproductive toxicity. METHODS: Isolated rat's theca interstitial cells (TICs) were treated with two typical (chlorpromazine [CPZ] and haloperidol [HAL]) and two atypical APs (risperidone [RIS] and clozapine [CLZ])...
March 17, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28277162/modulation-of-chemotherapy-induced-cytotoxicity-in-sh-sy5y-neuroblastoma-cells-by-caffeine-and-chlorogenic-acid
#6
Susan Hall, Shailendra Anoopkumar-Dukie, Gary D Grant, Ben Desbrow, Richard Lai, Devinder Arora, Yinna Hong
Chemotherapy is an important treatment modality for malignancy but is limited by significant toxicity and it susceptibility to numerous drug interactions. While the interacting effects with medications are well known, there is limited evidence on the interaction with commonly consumed food and natural products. The aim of this study was to evaluate the bioactive constituents of coffee (caffeine and chlorogenic acid) on the cytotoxicity of doxorubicin, gemcitabine, and paclitaxel in vitro. Pretreatment with caffeine (100 nM and 10 μM) sensitized SH-SY5Y cells to doxorubicin-induced toxicity and increased apoptosis and sensitized PC3 cells to gemcitabine-induced toxicity...
March 6, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28260084/toxicity-study-of-oxalicumone-a-derived-from-a-marine-derived-fungus-penicillium-oxalicum-in-cultured-renal-epithelial-cells
#7
Si Shi, Kunbin Guo, Xiangyu Wang, Hao Chen, Jianbin Min, Shuhua Qi, Wei Zhao, Weirong Li
Oxalicumone A (POA), a novel dihydrothiophene-condensed chromone, was isolated from the marine‑derived fungus Penicillium oxalicum. Previous reports demonstrated that POA exhibits strong activity against human carcinoma cells, thus it has been suggested as a bioactive anticancer agent. To research the toxic effect of POA on cultured normal epithelial human kidney‑2 (HK‑2) cells and evaluate its clinical safety, cell survival was evaluated by the Cell Counting Kit-8 assay and apoptosis was evaluated by Hoechst 33258 staining, flow cytometry, caspase‑3 activity assay and western blotting...
March 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28259903/siamese-crocodile-bile-induces-apoptosis-in-nci-h1299-human-non-small-cell-lung-cancer-cells-via-a-mitochondria-mediated-intrinsic-pathway-and-inhibits-tumorigenesis
#8
Ling Tian, Yi-Tao Deng, Xin Dong, Jia-Yi Fan, Hua-Liang Li, Yu-Mei Ding, Wei-Xi Peng, Qing-Xi Chen, Dong-Yan Shen
Non-small-cell lung cancer (NSCLC) is a widespread and particularly aggressive form of cancer. Patients with NSCLC and early metastases typically have poor prognosis, highlighting the critical need for additional drugs to improve disease outcome following surgical resection. The present study aimed to determine if Siamese crocodile bile (SCB) had an anti‑cancer effect on NCI‑H1299 human NSCLC cells. The inhibitory mechanism of SCB was examined in cell culture and nude mice. In vitro experimental results revealed that SCB inhibited the proliferation and colony‑forming ability of NCI‑H1299 cells by arresting cell cycle and inducing apoptosis...
February 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28259702/in-vitro-cardiotoxicity-assessment-of-environmental-chemicals-using-an-organotypic-human-induced-pluripotent-stem-cell-derived-model
#9
Oksana Sirenko, Fabian A Grimm, Kristen R Ryan, Yasuhiro Iwata, Weihsueh A Chiu, Frederick Parham, Jessica A Wignall, Blake Anson, Evan F Cromwell, Mamta Behl, Ivan Rusyn, Raymond R Tice
An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs...
March 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28257038/establishment-of-hk-2-cells-as-a-relevant-model-to-study-tenofovir-induced-cytotoxicity
#10
Rachel A Murphy, Reagan M Stafford, Brooke A Petrasovits, Megann A Boone, Monica A Valentovic
Tenofovir (TFV) is an antiviral drug approved for treating Human Immunodeficiency Virus (HIV) and Hepatitis B. TFV is administered orally as the prodrug tenofovir disoproxil fumarate (TDF) which then is deesterified to the active drug TFV. TFV induces nephrotoxicity characterized by renal failure and Fanconi Syndrome. The mechanism of this toxicity remains unknown due to limited experimental models. This study investigated the cellular mechanism of cytotoxicity using a human renal proximal tubular epithelial cell line (HK-2)...
March 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28236767/triggering-autophagic-cell-death-with-a-di-manganese-ii-developmental-therapeutic
#11
Creina Slator, Zara Molphy, Vickie McKee, Andrew Kellett
There is an unmet need for novel metal-based chemotherapeutics with alternative modes of action compared to clinical agents such as cisplatin and metallo-bleomycin. Recent attention in this field has focused on designing intracellular ROS-mediators as powerful cytotoxins of human cancers and identifying potentially unique toxic mechanisms underpinning their utility. Herein, we report the developmental di-manganese(II) therapeutic [Mn2(μ-oda)(phen)4(H2O)2][Mn2(μ-oda)(phen)4(oda)2]·4H2O (Mn-Oda) induces autophagy-promoted apoptosis in human ovarian cancer cells (SKOV3)...
February 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28179191/photosensitizer-mediated-mitochondria-targeting-nanosized-drug-carriers-subcellular-targeting-therapeutic-and-imaging-potentials
#12
Yeon Su Choi, Kiyoon Kwon, Kwonhyeok Yoon, Kang Moo Huh, Han Chang Kang
Mitochondria-targeting drug carriers have considerable potential because of the presence of many molecular drug targets in the mitochondria and their pivotal roles in cellular viability, metabolism, maintenance, and death. To compare the mitochondria-targeting abilities of triphenylphosphonium (TPP) and pheophorbide a (PhA) in nanoparticles (NPs), this study prepared mitochondria-targeting NPs using mixtures of methoxy poly(ethylene glycol)-(SS-PhA)2 [mPEG-(SS-PhA)2 or PPA] and TPP-b-poly(ε-caprolactone)-b-TPP [TPP-b-PCL-b-TPP or TPCL], which were designated PPAn-TPCL4-n (0≤n≤4) NPs...
February 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28169456/evaluating-the-protective-effects-and-mechanisms-of-diallyl-disulfide-on-interlukin-1%C3%AE-induced-oxidative-stress-and-mitochondrial-apoptotic-signaling-pathways-in-cultured-chondrocytes
#13
Azam Hosseinzadeh, Davood Jafari, Tunku Kamarul, Abolfazll Bagheri, Ali M Sharifi
The protective effects and mechanisms of DADS on IL-1β-mediated oxidative stress and mitochondrial apoptosis were investigated in C28I2 human chondrocytes. The effect of various concentrations of DADS (1, 5 10, 25, 50, and 100 μM) on C28I2 cell viability was evaluated in different times (2, 4, 8, 16, and 24 h) to obtain the non-cytotoxic concentrations of drug by MTT-assay. The protective effect of non-toxic concentrations of DADS on experimentally induced oxidative stress and apoptosis by IL-1β in C28I2 was evaluated...
February 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28165738/a-novel-potent-anticancer-compound-optimized-from-a-natural-oridonin-scaffold-induces-apoptosis-and-cell-cycle-arrest-through-the-mitochondrial-pathway
#14
Shengtao Xu, Hong Yao, Shanshan Luo, Yun-Kai Zhang, Dong-Hua Yang, Dahong Li, Guangyu Wang, Mei Hu, Yangyi Qiu, Xiaoming Wu, Hequan Yao, Weijia Xie, Zhe-Sheng Chen, Jinyi Xu
The cytotoxicity of the natural ent-kaurene diterpenoid, oridonin, has been extensively studied. However, the application of oridonin for cancer therapy was hampered primarily by its moderate potency. In this study, a series of oridonin A-ring modified analogues, and their derivatives bearing various substituents on 14-OH position, were designed, synthesized and evaluated for anticancer efficacy. Some of the derivatives were significantly more potent than oridonin against both drug-sensitive and drug-resistant cancer cells...
February 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28165491/anodically-grown-titania-nanotube-induced-cytotoxicity-has-genotoxic-origins
#15
M Sheikh Mohamed, Aida Torabi, Maggie Paulose, D Sakthi Kumar, Oomman K Varghese
Nanoarchitectures of titania (TiO2) have been widely investigated for a number of medical applications including implants and drug delivery. Although titania is extensively used in the food, drug and cosmetic industries, biocompatibility of nanoscale titania is still under careful scrutiny due to the conflicting reports on its interaction with cellular matter. For an accurate insight, we performed in vitro studies on the response of human dermal fibroblast cells toward pristine titania nanotubes fabricated by anodic oxidation...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28164768/protective-effect-of-aspirin-against-oligomeric-a%C3%AE-42-induced-mitochondrial-alterations-and-neurotoxicity-in-differentiated-ec-p19-neuronal-cells
#16
Hamendra Singh Parmar, Zbynek Houdek, Martin Pesta, Vaclava Cerna, Pavel Dvorak, Jiri Hatina
Amyloid-beta (Aβ) induced mitochondrial dysfunction is one of the major causes of neuronal toxicity in Alzheimer's disease. Many recent reports suggest involvement of mitochondrial alterations through intracellular accumulation of oligomeric Aβ. These mitochondrial alterations include increased reactive oxygen species (ROS), mt-DNA depletion, decreased oxidative phosphorylation and ATP production, membrane depolarization, reduced number of mitochondria etc. These all defects cumulatively caused neural toxicity and alterations in cellular energy homeostasis...
February 2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28161458/effect-of-mptp-on-mrna-expression-of-pgc-1%C3%AE-in-mouse-brain
#17
Rita Torok, Andras Salamon, Evelin Sumegi, Denes Zadori, Gabor Veres, Mate Fort Molnar, Laszlo Vecsei, Peter Klivenyi
The peroxisome proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC-1α) is a key regulator of mitochondrial biogenesis, respiration and adaptive thermogenesis. Besides the full-length protein (FL-PGC-1α), several other functionally active PGC-1α isoforms were identified as a result of alternative splicing (e.g., N-truncated PGC-1α; NT-PGC-1α) or alternative promoter usage (e.g., central nervous system-specific PGC-1α isoforms; CNS-PGC-1α). Achieving neuroprotection via CNS-targeted pharmacological stimulation is limited due to poor penetration of the blood brain barrier (BBB) by the proposed pharmaceutical agents, so preconditioning emerged as another option...
February 1, 2017: Brain Research
https://www.readbyqxmd.com/read/28157650/urb597-reduces-biochemical-behavioral-and-morphological-alterations-in-two-neurotoxic-models-in-rats
#18
Marisol Maya-López, Hipolito A Ruiz-Contreras, María de Jesús Negrete-Ruíz, Julián Elías Martínez-Sánchez, Juan Benítez-Valenzuela, Ana Laura Colín-González, Juana Villeda-Hernández, Laura Sánchez-Chapul, Carmen Parra-Cid, Edgar Rangel-López, Abel Santamaría
BACKGROUND: URB597 is a compound largely linked to the inhibition of fatty acid amide hydrolase (FAAH), an enzyme responsible for the metabolic degradation of the endocannabinoid anandamide (AEA). Despite this pharmacological property accounts for its modulatory profile demonstrated in some neurotoxic paradigms, the possible protective properties of this agent have been poorly investigated, and deserve exploration in different neurotoxic models. In this study, we explored the effects of URB597 on oxidative damage to lipids and other major endpoints of toxicity in two neurotoxic models in vivo in rats (the first one produced by the mitochondrial neurotoxin 3-nitropropionic acid [3-NP], and the other generated by the striatal injection of the pro-oxidant toxin 6-hydroxidopamine [6-OHDA]) in order to provide further supporting evidence of its modulatory profile...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28151485/photo-activation-of-the-delocalized-lipophilic-cation-d112-potentiates-cancer-selective-ros-production-and-apoptosis
#19
Ning Yang, Michael Weinfeld, Hélène Lemieux, Ben Montpetit, Ing Swie Goping
Delocalized lipophilic cations (DLCs) selectively accumulate in cancer cell mitochondria and have long been explored for therapeutic applications. Although targeted effects to cancer cells are demonstrated in vitro, non-specific toxicities in vivo have hampered clinical development. Identifying the molecular mechanisms of action and enhancing selectivity are thus necessary next steps to improve these compounds and evaluate their suitability for further drug development. D112 is one such DLC with promising properties...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28118671/mechanistic-approach-for-toxic-effects-of-bupropion-in-primary-rat-hepatocytes
#20
Elham Ahmadian, Hossein Babaei, Alireza Mohajjel Nayebi, Aziz Eftekhari, Mohammad Ali Eghbal
Bupropion is a widely prescribed antidepressant/smoke cessation drug. However, hepatotoxicity is one of its side effects reported in some recipients. The mechanisms by which bupropion induces hepatotoxicity is not clear yet. This experiment was intended to assess the cytotoxic mechanisms of bupropion toward primary rat hepatocytes. Additionally, the effect of α-tocopherol succinate (ALPHA-TOS) and N-acetyl cysteine (NAC) and mitochondrial permeability transition (MPT) pore sealing agent cyclosporine A (Cs A) on this toxicity was investigated...
January 24, 2017: Drug Research
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