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Drug induced mitochondrial toxicity

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https://www.readbyqxmd.com/read/28929270/mode-of-treatment-governs-curcumin-response-on-doxorubicin-induced-toxicity-in-cardiomyoblasts
#1
Aditi Jain, Vibha Rani
Doxorubicin (Dox) is an effective anti-cancer drug with severe reported cardiotoxicity. Cardiovascular risks associated with present cancer therapeutics demand urgent attention. There has been a growing interest in naturally occurring compounds to improve the therapeutic index as well as prevent non-tumour tissues from sustaining chemotherapy-induced damages. In the present study, the effects of curcumin, a polyphenol isolated from Curcuma longa and well known for its anti-oxidative, anti-cancerous and anti-inflammatory properties, was studied in relation to the Dox-induced cardiotoxicity...
September 19, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28900849/neuroprotective-effects-of-kinetin-against-glutamate-induced-oxidative-cytotoxicity-in-ht22-cells-involvement-of-nrf2-and-heme-oxygenase-1
#2
Yunpeng Wei, Dan Liu, Yin Zheng, Chaoshuang Hao, Honglian Li, Wuqing Ouyang
Oxidative stress is considered as one of key factors related to Alzheimer's disease (AD), while kinetin (KT) has been reported to exert anti-oxidative activities as well as neuroprotective effects both in vivo and in vitro. Thus, in this study, the neuroprotective effects of KT against glutamate-induced oxidative toxicity in HT22 cells were investigated. To evaluate the anti-oxidative capabilities of KT itself, several anti-oxidative assays in vitro were conducted. To evaluate the neuroprotective effects of KT, the levels of intracellular reactive oxygen species (ROS) and calcium influx, mitochondrial membrane potential (MMP), and cell death were measured by flow cytometry...
September 12, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28898759/cuprous-oxide-nanoparticles-trigger-er-stress-induced-apoptosis-by-regulating-copper-trafficking-and-overcoming-resistance-to-sunitinib-therapy-in-renal-cancer
#3
Qiwei Yang, Ye Wang, Qing Yang, Yi Gao, Xiaopeng Duan, Qingcheng Fu, Chuanmin Chu, Xiuwu Pan, Xingang Cui, Yinghao Sun
While the current standard first-line treatment for advanced renal cell carcinoma (RCC) is sunitinib, patients inevitably develop resistance to this drug. However, the rapid development of nanotechnology has provided emerging techniques for the treatment of advanced tumours, including RCC. In our previous research, cuprous oxide nanoparticles (CONPs) showed ideal anti-tumour effects and low systemic toxicity. While many inorganic nanomedicines, including CONPs, have similar pharmacological effects, their detailed mechanisms remain unknown...
September 5, 2017: Biomaterials
https://www.readbyqxmd.com/read/28881289/efficacy-of-a-series-of-alpha-pyrone-derivatives-against-leishmania-l-infantum-and-trypanosoma-cruzi
#4
Andre Gustavo Tempone, Daiane Dias Ferreira, Marta Lopes Lima, Thais Alves Costa Silva, Samanta E T Borborema, Juliana Quero Reimão, Mariana K Galuppo, Juliana Mariotti Guerra, Angelie J Russell, Graham M Wynne, Roy Y L Lai, Melissa M Cadelis, Brent R Copp
The neglected tropical diseases Chagas disease and leishmaniasis affect together more than 20 million people living mainly in developing countries. The mainstay of treatment is chemotherapy, however the drugs of choice, which include benznidazole and miltefosine, are toxic and have numerous side effects. Safe and effective therapies are urgently needed. Marine alpha-pyrones have been previously identified as scaffolds with potential antiprotozoan activities. In this work, using a phenotypic screen, twenty-seven examples of 3-substituted 4-hydroxy-6-methyl alpha-pyrones were synthesized and their antiparasitic efficacy evaluated against Leishmania (L...
September 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28871597/activation-of-the-mitochondrial-apoptotic-pathway-contributes-to-methotrexate-induced-small-intestinal-injury-in-rats
#5
Kasthuri Natarajan, Premila Abraham, Rekha Kota
The efficacy of methotrexate (MTX), a commonly used chemotherapeutic drug, is limited by intestinal injury. As the mechanism of MTX-induced small intestinal injury is not clear, there is no definitive treatment for MTX-induced gastrointestinal injury. The present study investigates the role of mitochondrial apoptotic pathway in MTX-induced small intestinal injury and examines whether aminoguanidine is effective in preventing the damage. Eight Wistar rats were administered 3 consecutive i.p. injections of 7 mg/kg body wt...
September 4, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28853863/nuclear-and-mitochondrial-dna-methylation-patterns-induced-by-valproic-acid-in-human-hepatocytes
#6
Jarno E J Wolters, Simone G J van Breda, Florian Caiment, Sandra M Claessen, Theo M C M de Kok, Jos C S Kleinjans
Valproic acid (VPA) is one of the most widely prescribed antiepileptic drugs in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis through mitochondrial dysfunction. The aim of this study is to further investigate VPA-induced mechanisms of steatosis by analyzing changes in patterns of methylation in nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Therefore, primary human hepatocytes (PHHs) were exposed to an incubation concentration of VPA that was shown to cause steatosis without inducing overt cytotoxicity...
September 13, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28846180/synergistic-activity-of-sorafenib-and-betulinic-acid-against-clonogenic-activity-of-non-small-cell-lung-cancer-cells
#7
Justyna Kutkowska, Leon Strzadala, Andrzej Rapak
The highly selective multi-targeted agent - sorafenib - is an inhibitor of a number of intracellular signaling kinases with anti-proliferative, anti-angiogenic and pro-apoptotic effects in various types of tumors, including human non-small cell lung cancer (NSCLC). Betulin displays a broad spectrum of biological and pharmacological properties, including the anticancer and chemopreventive activity. Combination of drugs with different targets is a logical approach to overcome multilevel cross-stimulation among key signaling pathways in NSCLC progression...
August 28, 2017: Cancer Science
https://www.readbyqxmd.com/read/28820078/effects-of-excitotoxic-lesion-with-inhaled-anesthetics-on-nervous-system-cells-of-rodents
#8
Maria Fernanda Quiroz Padilla, Gemma Guillazo-Blanch, Magdy Sanchez, Maria Andrea Dominguez, Rosa Margaria Gomez
Different anesthesia methods can variably influence excitotoxic lesion effects on the brain. The main purpose of this review is to identify potential differences in the toxicity to nervous system cells of two common inhalation anesthesia methods, isoflurane and sevoflurane, used in combination with an excitotoxic lesion procedure in rodents. The use of bioassays in animal models has provided the opportunity to examine the role of specific molecules and cellular interactions that underlie important aspects of neurotoxic effects relating to calcium homeostasis and apoptosis activation...
August 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28792756/design-synthesis-and-biological-evaluation-of-novel-selenium-containing-isocombretastatins-and-phenstatins-as-antitumor-agents
#9
Yanqing Pang, Baijiao An, Lanlan Lou, Junsheng Zhang, Jun Yan, Ling Huang, Xingshu Li, Sheng Yin
Two series of structurally related organoselenium compounds designed by fusing the anticancer agent methyl(phenyl)selane into the tubulin polymerization inhibitors isocombretastatins or phenstatins were synthesized and evaluated for antiproliferative activity. Most of these selenium containing hybrids exhibited potent cytotoxicity against a panel of cancel cell lines, with IC50 values in the submicromolar concentration range. Among them, 11a, the 3-methylseleno derivative of isocombretastatin A-4 (isoCA-4) represented the most active compound with IC50 values of 2-34 nM against 12 cancer cell lines, including two drug-resistant cell lines...
August 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28776290/synthesis-characterization-and-evaluation-of-cd-l-proline-2-a-novel-histone-deacetylase-inhibitor-that-induces-epigenetic-modification-of-histone-deacetylase-isoforms-in-a549-cells
#10
Anusha Chidambaram, Arunachalam Sekar, Kavya S H, Ramesh Kumar Chidambaram, Kalaiarasi Arunachalam, Senthilkumar G P, Ravikumar Vilwanathan
Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression through their effects on the compact chromatin structure. In clinical studies, several classes of histone deacetylase inhibitors (HDACi) have demonstrated potent anticancer activities with metal complexes. Hence, we synthesized cadmium-proline complexes using both the D- and L-isomers of proline and evaluated their biological activities by observing the efficiency of their inhibition of HDAC activity, ability to reduce the expression of HDAC isoforms in A549 cells and effect on apoptosis...
August 3, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28762043/customised-in-vitro-model-to-detect-human-metabolism-dependent-idiosyncratic-drug-induced-liver-injury
#11
Laia Tolosa, Nuria Jiménez, Gabriela Pérez, José V Castell, M José Gómez-Lechón, M Teresa Donato
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify metabolic phenotypes with increased susceptibility to DILI...
July 31, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28759731/antibiotic-drug-piperacillin-induces-neuron-cell-death-through-mitochondrial-dysfunction-and-oxidative-damage
#12
Shan Jiang, Tong Li, Xiao Zhou, Wenjun Qin, Zijun Wang, Yi Liao
Although nerve damage/toxicity has been shown to be one of the side effects in patients given prolonged antibiotic treatment, the mechanisms of the action of antibiotics on neuron cells are not clear. In this work, we investigated the toxicity of piperacillin (an antibiotic that can penetrate blood-brain barrier) on neuron cells and its underlying mechanisms. We show that clinically relevant doses of piperacillin induce apoptosis in SH-SY5Y and human primary neuron cells through activating caspase 3 activity and decreasing Mcl-1 and Bcl-2 levels...
July 31, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28757873/absence-of-relationship-between-mitochondrial-dna-haplogroups-and-cisplatin-induced-hearing-loss
#13
D Graterol, C Mir, C Garcia-Vaquero, I Braña, A N Pardo, M I Rochera-Villach, A Lyakhovich, M E LLeonart, J Lorente
BACKGROUND: Many drugs used for cancer chemotherapy produce reactive oxygen species, thus leading to various complications including nephrotoxicity, cardiotoxicity, and ototoxicity. OBJECTIVE: We have provided a haplogroup analysis of a cohort of cancer patients treated with chemotherapy and compared factors associated with associated hearing loss. STUDY DESIGN AND METHODS: This observational cohort study includes a pure-tone audiometry of the patients who underwent chemotherapeutic treatment...
2017: International Journal of Otolaryngology
https://www.readbyqxmd.com/read/28754872/tunicamycin-induced-endoplasmic-reticulum-stress-promotes-apoptosis-of-prostate-cancer-cells-by-activating-mtorc1
#14
Prasun Guha, Engin Kaptan, Padmaja Gade, Dhananjaya V Kalvakolanu, Hafiz Ahmed
Studies suggest that tunicamycin may work as a therapeutic drug to cancer cells by inducing stress in the endoplasmic reticulum (ER) through unfolded protein response (UPR) and thereby promoting apoptosis. However, mechanisms of the prolonged activation of the UPR under sustained ER stress in the regulation of cell apoptosis are largely unknown. To delineate the role of candidate genes in the apoptotic process under ER stress and to search for new therapeutic strategies to treat metastatic castration resistant prostate cancer, we performed whole genome expression microarray analysis in tunicamycin treated metastatic androgen-insensitive prostate cancer cells, PC-3...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28748471/evaluation-of-mitochondrial-respiration-in-cultured-rat-hepatocytes
#15
Jean-Pierre Marchandeau, Gilles Labbe
Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects, such as lactic acidosis and rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can be performed in order to determine if drugs can disturb mitochondrial fatty acid oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial permeability transition pore (MPT). Among these investigations, mitochondrial respiration is a relatively easy test to measure the potential toxicity of a drug...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28748373/novel-combination-of-salinomycin-and-resveratrol-synergistically-enhances-the-anti-proliferative-and-pro-apoptotic-effects-on-human-breast-cancer-cells
#16
Jayant Dewangan, Divya Tandon, Sonal Srivastava, Ajeet Kumar Verma, Ashok Yapuri, Srikanta Kumar Rath
Resveratrol (RES) is a natural polyphenol having anti-proliferative activity against breast cancer cells. RES in combination with other chemo modulatory agents, minimizes toxicity and increases efficacy of the treatment. Salinomycin (SAL), a monocarboxylic polyether ionophore is known for selectively targeting breast cancer stem cells. Purpose of the present study was to investigate whether RES in combination with SAL exerts synergistic anti-proliferative activity on breast cancer cells. We further evaluated the molecular mechanism behind SAL and RES mediated cell death...
July 26, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28733192/pharmacological-evaluation-of-phytochemicals-from-south-indian-black-turmeric-curcuma-caesia-roxb-to-target-cancer-apoptosis
#17
K S Mukunthan, R S Satyan, T N Patel
Curcuma caesia Roxb. (Black turmeric), a perennial herb of the family Zingiberaceae is indigenous to India. C. caesia is used as a spice, food preservative and coloring agent commonly in the Indian subcontinent. Functional parametric pharmacological evaluations like drug ability and toxicity profile of this endangered species is poorly documented. In our present study, among all the extracts of dried C. caesia rhizome viz- hexane, ethyl acetate, methanol and water tested for free radical scavenging capacity by total antioxidant activity (TAO) method, Hexane Rhizome Extract (HRE) was found to possess remarkable activity (1200mg ascorbic acid equivalent/100g)...
September 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28726777/humanin-g-hng-protects-age-related-macular-degeneration-amd-transmitochondrial-arpe-19-cybrids-from-mitochondrial-and-cellular-damage
#18
Sonali Nashine, Pinchas Cohen, Marilyn Chwa, Stephanie Lu, Anthony B Nesburn, Baruch D Kuppermann, M Cristina Kenney
Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28722244/risk-of-liver-decompensation-with-cumulative-use-of-mitochondrial-toxic-nucleoside-analogues-in-hiv-hepatitis-c-virus-coinfection
#19
Vincent Lo Re Rd, Bret Zeldow, Michael J Kallan, Janet P Tate, Dena M Carbonari, Sean Hennessy, Jay R Kostman, Joseph K Lim, Matthew Bidwell Goetz, Robert Gross, Amy C Justice, Jason A Roy
PURPOSE: Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death. METHODS: We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients...
July 19, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28705594/induction-of-abcg2-bcrp-restricts-the-distribution-of-zidovudine-to-the-fetal-brain-in-rats
#20
María Fernanda Filia, Timoteo Marchini, Juan Mauricio Minoia, Martín Ignacio Roma, Fernanda Teresa De Fino, Modesto Carlos Rubio, Guillermo J Copello, Pablo A Evelson, Roxana Noemí Peroni
Safety concerns for fetus development of zidovudine (AZT) administration as prophylaxis of vertical transmission of HIV persist. We evaluated the participation of the ATP-binding cassette efflux transporter ABCG2 in the penetration of AZT into the fetal brain and the relevance for drug safety. Oral daily doses of AZT (60mg/kg body weight) or its vehicle were administered between post gestational days 11 (E11) and 20 (E20) to Sprague-Dawley pregnant rats. At E21, animals received an intravenous bolus of 60mg AZT/kg body weight in the presence or absence of the ABCG2 inhibitor gefitinib (20mg/kg body weight, ip) and AZT in maternal plasma and fetal brain were measured by HPLC-UV...
September 1, 2017: Toxicology and Applied Pharmacology
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