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Drug induced mitochondrial toxicity

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https://www.readbyqxmd.com/read/28102525/environmental-chemicals-and-aging
#1
REVIEW
Brandon L Pearson, Dan Ehninger
PURPOSE OF REVIEW: Innovations in agriculture and medicine as well as industrial and domestic technologies are essential for the growing and aging global population. These advances generally require the use of novel natural or synthetic chemical agents with the potential to affect human health. Here, we attempt to highlight environmental chemicals and select drugs with the potential to exacerbate aging by directly affecting molecular aging cascades focusing particular attention on the brain...
January 19, 2017: Current Environmental Health Reports
https://www.readbyqxmd.com/read/28101470/protective-roles-of-n-acetyl-cysteine-and-or-taurine-against-sumatriptan-induced-hepatotoxicity
#2
Javad Khalili Fard, Hossein Hamzeiy, Mohammadreza Sattari, Mohammad Ali Eghbal
Purpose: Triptans are the drug category mostly prescribed for abortive treatment of migraine. Most recent cases of liver toxicity induced by triptans have been described, but the mechanisms of liver toxicity of these medications have not been clear. Methods: In the present study, we obtained LC50 using dose-response curve and investigated cell viability, free radical generation, lipid peroxide production, mitochondrial injury, lysosomal membrane damage and the cellular glutathione level as toxicity markers as well as the beneficial effects of taurine and/or N-acetyl cysteine in the sumatriptan-treated rat parenchymal hepatocytes using accelerated method of cytotoxicity mechanism screening...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28101220/antitumor-effect-of-forbesione-isolated-from-garcinia-hanburyi-on-cholangiocarcinoma-in-vitro-and-in-vivo
#3
Parichart Boueroy, Chariya Hahnvajanawong, Thidarut Boonmars, Sunitta Saensa-Ard, Natthinee Anantachoke, Kulthida Vaeteewoottacharn, Vichai Reutrakul
Cholangiocarcinoma (CCA) is a malignancy with no effective therapy and poor prognosis. Forbesione, a caged xanthone isolated from Garcinia hanburyi, has been reported to inhibit proliferation and to induce apoptosis in human CCA cell lines. The present study aimed to further explore the potential anticancer properties of forbesione by testing its effects against the hamster CCA cell line Ham-1 in vitro and in vivo. It was observed that forbesione inhibited the growth of Ham-1 cells in vitro and suppressed Ham-1 growth as allograft in hamsters by inducing cell cycle arrest at the S phase...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28088732/apelin-13-protects-rat-primary-cortical-glia-neuron-co-culture-against-pentylenetetrazole-induced-toxicity
#4
Taj Pari Kalantaripour, Saeed Esmaeili-Mahani, Vahid Sheibani, Hamid Najafipour, Majid Asadi-Shekaari M
In spite of recent advances in the treatment of epilepsy, up to 35% of people living with the condition do not respond to accessible anti-epileptic drugs (AEDs) and continue to experience regular, devastating and potentially life-threatening seizures. Neuronal death is a significant feature of epilepsy in humans and experimental models. It has been reported that apelin, an endogenous ligand for the angiotensin-1-like receptor (APJ), has anticonvulsive as well as protective effects in some neurodegenerative situations...
January 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28088622/reactive-oxygen-species-and-cancer-paradox-to-promote-or-to-suppress
#5
REVIEW
Sehamuddin Galadari, Anees Rahman, Siraj Pallichankandy, Faisal Thayyullathil
Reactive oxygen species (ROS), a group of highly reactive ions and molecules, are increasingly being appreciated as powerful signaling molecules involved in the regulation of a variety of biological processes. Indeed, their role is continuously being delineated in a variety of pathophysiological conditions. For instance, cancer cells are shown to have increased ROS levels in comparison to their normal counterparts. This is partly due to an enhanced metabolism and mitochondrial dysfunction in cancer cells. The escalated ROS generation in cancer cells contributes to the biochemical and molecular changes necessary for the tumor initiation, promotion and progression, as well as, tumor resistance to chemotherapy...
January 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28078787/targeting-nasopharyngeal-carcinoma-by-artesunate-through-inhibiting-akt-mtor-and-inducing-oxidative-stress
#6
Qin Li, Wei Ni, Zhifeng Deng, Minghe Liu, Lazhi She, Qiong Xie
Drug repurposing has become an alternative therapeutic strategy for cancer treatment given the known pharmacokinetics and toxicity. The inhibitory effects of artesunate have been reported in various cancers. In this work, we investigated the effects of artesunate in nasopharyngeal carcinoma (NPC). We demonstrate that artesunate significantly inhibits proliferation via arresting NPC cells at G2/M phase. It also induces apoptosis through caspase-dependent and mitochondria-independent pathways in multiple NPC cell lines...
January 11, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28078613/l-f001-a-multifunction-rock-inhibitor-prevents-6-ohda-induced-cell-death-through-activating-akt-gsk-3beta-and-nrf2-ho-1-signaling-pathway-in-pc12-cells-and-attenuates-mptp-induced-dopamine-neuron-toxicity-in-mice
#7
Liting Luo, Jingkao Chen, Dan Su, Meihui Chen, Bingling Luo, Rongbiao Pi, Lan Wang, Wei Shen, Rikang Wang
Amounting evidences demonstrated that Rho/Rho-associated kinase (ROCK) might be a novel target for the therapy of Parkinson's disease (PD). Recently, we synthesized L-F001 and revealed it was a potent ROCK inhibitor with multifunctional effects. Here we investigated the effects of L-F001 in PD models. We found that L-F001 potently attenuated 6-OHDA-induced cytotoxicity in PC12 cells and significantly decreased intracellular reactive oxygen species (ROS), prevented the 6-OHDA-induced decline of mitochondrial membrane potential and intracellular GSH levels...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28073120/nano-pelargonidin-protects-hyperglycemic-induced-l6-cells-against-mitochondrial-dysfunction
#8
Asmita Samadder, Debojyoti Tarafdar, Suresh K Abraham, Kumaresh Ghosh, Anisur Rahman Khuda-Bukhsh
Nano-encapsulation of several natural products has become an important tool in enhancing the bioavailability of some modern drugs against many diseases. Pelargonidin is an anthocyanidin found in many fruits and vegetables. Pelargonidin is loaded with poly-lactide-co-glycolic-acid, a non-toxic biodegradable polymer, to produce nano-pelargonidin. Size, morphology, zeta potential, and planar uniformity of formulated nano-pelargonidin were determined by atomic force microscopy and dynamic light scattering. The time required for cellular entry, folds of nano-pelargonidin, and drug encapsulation efficiency of poly-lactide-co-glycolic-acid were also ascertained...
January 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28068992/hyaluronic-acid-coated-chitosan-nanoparticles-induce-ros-mediated-tumor-cell-apoptosis-and-enhance-antitumor-efficiency-by-targeted-drug-delivery-via-cd44
#9
Tao Wang, Jiahui Hou, Chang Su, Liang Zhao, Yijie Shi
BACKGROUND: A targeted drug nanoparticle (NP) delivery system has shown potential as a possible cancer treatment. Given its merits, such as its selective distribution at tumor sites and its controllable drug release, drug-loaded NPs can be effectively delivered to selected organs and targeted cells, thus enhancing its antitumor efficiency and reducing its toxicity. METHODS: We reported that hyaluronic acid (HA)-coated chitosan NPs promoted the drug delivery of 5-fluorouracil (5-Fu) into tumor cells that highly expressed CD44...
January 10, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28053531/enhanced-photocytotoxicity-of-curcumin-delivered-by-solid-lipid-nanoparticles
#10
Shan Jiang, Rongrong Zhu, Xiaolie He, Jiao Wang, Mei Wang, Yechang Qian, Shilong Wang
Curcumin (Cur) is a promising photosensitizer that could be used in photodynamic therapy. However, its poor solubility and hydrolytic instability limit its clinical use. The aim of the present study was to encapsulate Cur into solid lipid nanoparticles (SLNs) in order to improve its therapeutic activity. The Cur-loaded SLNs (Cur-SLNs) were prepared using an emulsification and low-temperature solidification method. The functions of Cur and Cur-SLNs were studied on the non-small cell lung cancer A549 cells for photodynamic therapy...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28053072/the-promise-of-new-technologies-to-reduce-refine-or-replace-animal-use-while-reducing-risks-of-drug-induced-liver-injury-in-pharmaceutical-development
#11
Frank D Sistare, William B Mattes, Edward L LeCluyse
Drug induced liver injury (DILI) has contributed more to marketed pharmaceutical withdrawals and clinical development failures than any other human organ toxicity. DILI seen in animal studies also frequently leads to the discontinuation of promising drug candidates very early in the pipeline. This manuscript reviews and critically assesses the current regulatory expectations; the current drug development approaches, strategies, and gaps; and the numerous exciting opportunities becoming available to address these gaps through technological advances...
December 2016: ILAR Journal
https://www.readbyqxmd.com/read/28032146/effects-of-31-fda-approved-small-molecule-kinase-inhibitors-on-isolated-rat-liver-mitochondria
#12
Jun Zhang, Alec Salminen, Xi Yang, Yong Luo, Qiangen Wu, Matthew White, James Greenhaw, Lijun Ren, Matthew Bryant, William Salminen, Thomas Papoian, William Mattes, Qiang Shi
The FDA has approved 31 small-molecule kinase inhibitors (KIs) for human use as of November 2016, with six having black box warnings for hepatotoxicity (BBW-H) in product labeling. The precise mechanisms and risk factors for KI-induced hepatotoxicity are poorly understood. Here, the 31 KIs were tested in isolated rat liver mitochondria, an in vitro system recently proposed to be a useful tool to predict drug-induced hepatotoxicity in humans. The KIs were incubated with mitochondria or submitochondrial particles at concentrations ranging from therapeutic maximal blood concentrations (Cmax) levels to 100-fold Cmax levels...
December 28, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/28006933/nilotinib-induces-er-stress-and-cell-death-in-h9c2-cells
#13
D Lekes, I Szadvari, O Krizanova, K Lopusna, I Rezuchova, M Novakova, Z Novakova, T Parak, P Babula
Tyrosine kinases inhibitors (TKi) represent a relatively novel class of anticancer drugs that target cellular pathways overexpressed in certain types of malignancies, such as chronic myeloid leukaemia (CML). Nilotinib, ponatinib and imatinib exhibit cardiotoxic and vascular effects. In this study, we focused on possible cardiotoxicity of nilotinib using H9c2 cells as a suitable cell model. We studied role of endoplasmic reticulum (ER) stress and apoptosis in nilotinib toxicity using a complex approach. Nilotinib impaired mitochondrial function and induced formation of ROS under clinically relevant concentrations...
December 21, 2016: Physiological Research
https://www.readbyqxmd.com/read/27984590/competing-mechanistic-hypotheses-of-acetaminophen-induced-hepatotoxicity-challenged-by-virtual-experiments
#14
Andrew K Smith, Brenden K Petersen, Glen E P Ropella, Ryan C Kennedy, Neil Kaplowitz, Murad Ookhtens, C Anthony Hunt
Acetaminophen-induced liver injury in mice is a model for drug-induced liver injury in humans. A precondition for improved strategies to disrupt and/or reverse the damage is a credible explanatory mechanism for how toxicity phenomena emerge and converge to cause hepatic necrosis. The Target Phenomenon in mice is that necrosis begins adjacent to the lobule's central vein (CV) and progresses outward. An explanatory mechanism remains elusive. Evidence supports that location dependent differences in NAPQI (the reactive metabolite) formation within hepatic lobules (NAPQI zonation) are necessary and sufficient prerequisites to account for that phenomenon...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27941424/characterization-of-neurologic-and-ophthalmologic-safety-of-oral-administration-of-tedizolid-for-up-to-21-days-in-healthy-volunteers
#15
Edward Fang, Kelly A Muñoz, Philippe Prokocimer
BACKGROUND: Antibacterials that inhibit protein synthesis may be associated with mitochondrial toxicity, manifested as serious optic or peripheral neuropathy or myelosuppression. Tedizolid is a novel oxazolidinone antibacterial that may have reduced the potential for mitochondrial toxicity. STUDY QUESTION: Based on the results of 2 studies (NCT01623401 and NCT00671814) conducted early in the tedizolid development program, what is the potential for drug-induced optic and peripheral neuropathies with tedizolid treatment? METHODS: Two phase-1 studies were conducted in healthy volunteers...
November 15, 2016: American Journal of Therapeutics
https://www.readbyqxmd.com/read/27934920/functional-human-induced-hepatocytes-hiheps-with-bile-acid-synthesis-and-transport-capacities-a-novel-in-vitro-cholestatic-model
#16
Xuan Ni, Yimeng Gao, Zhitao Wu, Leilei Ma, Chen Chen, Le Wang, Yunfei Lin, Lijian Hui, Guoyu Pan
Drug-induced cholestasis is a leading cause of drug withdrawal. However, the use of primary human hepatocytes (PHHs), the gold standard for predicting cholestasis in vitro, is limited by their high cost and batch-to-batch variability. Mature hepatocyte characteristics have been observed in human induced hepatocytes (hiHeps) derived from human fibroblast transdifferentiation. Here, we evaluated whether hiHeps could biosynthesize and excrete bile acids (BAs) and their potential as PHH alternatives for cholestasis investigations...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27931237/a-piperazidine-derivative-of-23-hydroxy-betulinic-acid-induces-a-mitochondria-derived-ros-burst-to-trigger-apoptotic-cell-death-in-hepatocellular-carcinoma-cells
#17
Nan Yao, Ying-Jie Li, Yu-He Lei, Nan Hu, Wei-Min Chen, Zhe Yao, Miao Yu, Jun-Shan Liu, Wen-Cai Ye, Dong-Mei Zhang
BACKGROUND: Elevated production of reactive oxygen species (ROS) and an altered redox state have frequently been observed in hepatocellular carcinoma (HCC); therefore, selective killing of HCC cells by chemotherapeutic agents that stimulate ROS generation or impair antioxidant systems may be a feasible approach in HCC chemotherapy. Recently, betulinic acid and its derivatives have attracted attention because they showed anti-cancer effects via a ROS- and mitochondria-related mechanism...
December 8, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27913197/doxorubicin-induced-mitophagy-contributes-to-drug-resistance-in-cancer-stem-cells-from-hct8-human-colorectal-cancer-cells
#18
Chen Yan, Lan Luo, Chang-Ying Guo, Shinji Goto, Yoshishige Urata, Jiang-Hua Shao, Tao-Sheng Li
Cancer stem cells (CSCs) are known to be drug resistant. Mitophagy selectively degrades unnecessary or damaged mitochondria by autophagy during cellular stress. To investigate the potential role of mitophagy in drug resistance in CSCs, we purified CD133(+)/CD44(+) CSCs from HCT8 human colorectal cancer cells and then exposed to doxorubicin (DXR). Compared with parental cells, CSCs were more resistant to DXR treatment. Although DXR treatment enhanced autophagy levels in both cell types, the inhibition of autophagy by ATG7 silencing significantly increased the toxicity of DXR only in parental cells, not in CSCs...
November 30, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27861613/non-serotonergic-neurotoxicity-by-mdma-ecstasy-in-neurons-derived-from-mouse-p19-embryonal-carcinoma-cells
#19
Dina Popova, Andréas Forsblad, Sanaz Hashemian, Stig O P Jacobsson
3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays...
2016: PloS One
https://www.readbyqxmd.com/read/27859025/modeling-drug-induced-neuropathy-using-human-ipscs-for-predictive-toxicology
#20
R Ohara, K Imamura, F Morii, N Egawa, K Tsukita, T Enami, R Shibukawa, T Mizuno, M Nakagawa, H Inoue
Drugs under development can cause unpredicted toxicity in humans due to differential drug responsiveness between humans and other disease models, resulting in clinical trial failures. Human induced pluripotent stem cells (iPSCs) are expected to represent a useful tool for toxicity testing. However, among many assays, appropriate cellular assays for predicting neurotoxicity in an iPSC-based model are still uncertain. Here we generated neurons from iPSCs of Charcot-Marie-Tooth disease (CMT) patients. Some CMT patients are sensitive to anticancer drugs and present with an adverse reaction of neuropathy...
November 9, 2016: Clinical Pharmacology and Therapeutics
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