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Drug induced mitochondrial toxicity

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https://www.readbyqxmd.com/read/28511367/neurobehavioural-changes-in-a-hemiparkinsonian-rat-model-induced-by-rotenone
#1
REVIEW
Sukala Puthuparambil Maniyath, Narayanan Solaiappan, Muthusamy Rathinasamy
INTRODUCTION: Rotenone, a mitochondrial complex I inhibitor is used as a neurotoxin agent to reproduce the neuropathological, and behavioural feature of Parkinson's Disease (PD) in rat. Due to acute and chronic exposure of rotenone with various doses through different routes of administration, mortality is being reported. Low dose takes a longer duration to produce PD symptoms in animals. This present study was designed to create hemiparkinsonian 'partial' lesion model by rotenone at a single moderate dose in two sites of striatum in albino rats and also to assess its toxicity by behavioural parameters and by microscopic study...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28507435/mesoporous-silica-nanoparticles-trigger-mitophagy-in-endothelial-cells-and-perturb-neuronal-network-activity-in-a-size-and-time-dependent-manner
#2
Antonina Orlando, Emanuela Cazzaniga, Maria Tringali, Francesca Gullo, Andrea Becchetti, Stefania Minniti, Francesca Taraballi, Ennio Tasciotti, Francesca Re
PURPOSE: Mesoporous silica nanoparticles (MSNPs) are excellent candidates for biomedical applications and drug delivery to different human body areas, the brain included. Although toxicity at cellular level has been investigated, we are still far from using MSNPs in the clinic, because the mechanisms involved in the cellular responses activated by MSNPs have not yet been elucidated. MATERIALS AND METHODS: This study used an in vitro multiparametric approach to clarify relationships among size, dose, and time of exposure of MSNPs (0...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28496041/a-rapid-mitochondrial-toxicity-assay-utilizing-rapidly-changing-cell-energy-metabolism
#3
Yosuke Sanuki, Tetsuro Araki, Osamu Nakazono, Kazuyuki Tsurui
Drug-induced liver injury is a major cause of safety-related drug-marketing withdrawals. Several drugs have been reported to disrupt mitochondrial function, resulting in hepatotoxicity. The development of a simple and effective in vitro assay to identify the potential for mitochondrial toxicity is thus desired to minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in vitro test method called the "glucose-galactose" assay is often used in drug development but requires prior-culture of cells over several passages for mitochondrial adaptation, thereby restricting use of the assay...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28486401/drug-induced-liver-injury-cascade-of-events-leading-to-cell-death-apoptosis-or-necrosis
#4
REVIEW
Andrea Iorga, Lily Dara, Neil Kaplowitz
Drug-induced liver injury (DILI) can broadly be divided into predictable and dose dependent such as acetaminophen (APAP) and unpredictable or idiosyncratic DILI (IDILI). Liver injury from drug hepatotoxicity (whether idiosyncratic or predictable) results in hepatocyte cell death and inflammation. The cascade of events leading to DILI and the cell death subroutine (apoptosis or necrosis) of the cell depend largely on the culprit drug. Direct toxins to hepatocytes likely induce oxidative organelle stress (such as endoplasmic reticulum (ER) and mitochondrial stress) leading to necrosis or apoptosis, while cell death in idiosyncratic DILI (IDILI) is usually the result of engagement of the innate and adaptive immune system (likely apoptotic), involving death receptors (DR)...
May 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28466458/rip1-dependent-reactive-oxygen-species-production-executes-artesunate-induced-cell-death-in-renal-carcinoma-caki-cells
#5
Anil Kumar Chauhan, Kyoung-Jin Min, Taeg Kyu Kwon
Artesunate is a well-known anti-malarial drug originated from artemisinin as a Chinese herb and has been reported to have anti-cancer potential in many cancer cells. In the present study, we examined the efficacy of artesunate against the renal carcinoma Caki cells and explored its mechanism of cytotoxicity. A steep decline in cell viability within 18 h was recorded upon artesunate exposure, but pretreatment of z-VAD-FMK had no effect on the loss of the cell viability by artesunate. On the other hand, necrostatin-1 pretreatment and knockdown of RIP-1 significantly reduced the cytotoxicity of artesunate against Caki cell...
May 2, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28463418/use-of-primary-rat-hepatocytes-for-prediction-of-drug-induced-mitochondrial-dysfunction
#6
Cong Liu, Shuichi Sekine, Binbin Song, Kousei Ito
Mitochondrial dysfunction plays a central role in drug-induced liver injury. To evaluate drug-induced mitochondrial impairment, several isolated mitochondria- or cell line-based assays have been reported. Among them, culturing HepG2 cells in galactose provides a remarkable method to assess mitochondrial toxicity by activating mitochondrial aerobic respiration. We applied this assay to primary rat hepatocytes by culturing cells in galactose and hyperoxia to enhance the evaluation of metabolism-related drug-induced mitochondrial toxicity...
May 2, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/28458133/scutellarin-derivatives-as-apoptosis-inducers-design-synthesis-and-biological-evaluation
#7
Tong Han, Jia Li, Jingjing Xue, He Li, Fanxing Xu, Keguang Cheng, Dahong Li, Zhanlin Li, Ming Gao, Huiming Hua
To explore novel antitumor agents with high efficiency and low toxicity, a series of NO-donating scutellarin derivatives (14-17) were synthesized and the antiproliferative activities against MCF-7, HCT-116, PC-3 and HepG2 cancer cell lines were assessed. Among them, compound 14b was the strongest with IC50 values of 2.96 μM, 7.25 μM, 0.09 μM and 0.50 μM, respectively, and displayed low toxicity against normal human liver L-O2 cells with an IC50 of 47.96 μM, showing good selectivity between normal and malignant liver cells...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28456571/erythropoietin-activates-sirt1-to-protect-human-cardiomyocytes-against-doxorubicin-induced-mitochondrial-dysfunction-and-toxicity
#8
Lan Cui, Jiabin Guo, Qiang Zhang, Jian Yin, Jin Li, Wei Zhou, Tingfen Zhang, Haitao Yuan, Jun Zhao, Li Zhang, Paul L Carmichael, Shuangqing Peng
The hormone erythropoietin (EPO) has been demonstrated to protect against chemotherapy drug doxorubicin (DOX)-induced cardiotoxicity, but the underlying mechanism remains obscure. We hypothesized that silent mating type information regulation 2 homolog 1 (SIRT1), an NAD(+)-dependent protein deacetylase that activates peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), plays a crucial role in regulating mitochondrial function and mediating the beneficial effect of EPO. Our study in human cardiomyocyte AC16 cells showed that DOX-induced cytotoxicity and mitochondrial dysfunction, as manifested by decreased mitochondrial DNA (mtDNA) copy number, mitochondrial membrane potential, and increased mitochondrial superoxide accumulation, can be mitigated by EPO pretreatment...
April 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28456516/identification-of-novel-1-indolyl-acetate-5-nitroimidazole-derivatives-of-combretastatin-a-4-as-potential-tubulin-polymerization-inhibitors
#9
Yong-Fang Yao, Zhong-Chang Wang, Song-Yu Wu, Qing-Fang Li, Chen-Yu, Xin-Yi Liang, Peng-Cheng Lv, Yong-Tao Duan, Hai-Liang Zhu
Microtubules are essential for the mitotic division of cells and have become an attractive target for anti-tumour drugs due to the increased incidence of cancer and significant mitosis rate of tumour cells. In this study, a total of six indole 1-position modified 1-indolyl acetate-5-nitroimidazole derivatives were designed, synthesized, and evaluated for their ability to inhibit tubulin polymerization caused by binding to the colchicine-binding site of tubulin. Among them, compound 3 displayed the best ability to inhibit tubulin polymerization; it also exhibited better anti-proliferative activities than colchicine against a panel of human cancer cells (with IC50 values ranging from 15 to 40 nM), especially HeLa cells (with IC50 values of 15 nM), based on the cellular cytotoxicity assay results...
April 26, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28455219/ph-sensitive-polymeric-nanoparticles-for-co-delivery-of-doxorubicin-and-curcumin-to-treat-cancer-via-enhanced-pro-apoptotic-and-anti-angiogenic-activities
#10
Jinming Zhang, Jingjing Li, Zhi Shi, Yang Yang, Xi Xie, Simon MingYuen Lee, Yitao Wang, Kam W Leong, Meiwan Chen
Co-delivery of multiple drugs with complementary anticancer mechanisms by nano-carriers offers an effective strategy to treat cancer. The combination of drugs with pro-apoptotic and anti-angiogenic activities is potentially effective in treating human hepatocellular carcinoma (HCC). Herein, we developed a co-delivery system for doxorubicin (Dox), a pro-apoptotic drug, and curcumin (Cur), a potent drug for antiangiogenesis, in pH-sensitive nanoparticles (NPs) constituted with amphiphilic poly(β-amino ester) copolymer...
April 25, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28454919/new-amino-acid-schiff-base-derived-from-s-allyl-cysteine-and-methionine-alleviates-carbon-tetrachloride-induced-liver-dysfunction
#11
Periyasamy Ratha, Loganathan Chitra, Ancy Iruthayaraj, Poomani Kumaradhas, Thayumanavan Palvannan
In spite of the tremendous stride in modern medicine, conventional drugs used in the hepatotoxic management are mostly inadequate. The present study aims in the synthesis of novel Schiff base compound derived using s-ally cystiene and methionine. The newly synthesized compound, 2-((2-((2-(allylthio)-1-carboxyethyl)imino)ethylidene)amino)-4-(methylthio)butanoic acid (ACEMB) was characterized using UV-visible spectrophotometer, FTIR, (1)HNMR, and GC-MS. ACEMB showed potent in vitro antioxidant property. Chronic administration of ACEMB prior to CCl4 intoxication: i) attenuated the leakage of liver injury markers, such as, enzymes (AST, ALT, GGT, ALP and LDH) and biomolecules (bilirubin) into the blood circulation; ii) normalized the concentration of total proteins, albumin and globulin to control level; and iii) protected the liver against dyslipidemia...
April 25, 2017: Biochimie
https://www.readbyqxmd.com/read/28454894/the-antimalarial-drug-artemisinin-induces-an-additional-sod1-supressible-anti-mitochondrial-action-in-yeast
#12
Chen Sun, Bing Zhou
The molecular action of artemisinins (ARTs) is not well understood. To determine the molecular and cellular basis that might underlie their differential effects observed in anti-malarial and anti-cancer studies, we utilized the yeast Saccharomyces cerevisiae to examine their toxicity profiles and properties. Previously we reported that while both low levels (2-8μM) of artemisinin (ART) and dihydroartemisinin (DHA) partly depolarize the mitochondrial membranes, inhibiting yeast growth on non-fermentable media, only DHA at moderate levels (such as 40μM) potently represses yeast growth on fermentable media via a heme-mediated pathway...
April 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28447781/artemisinin-protectes-retinal-neuronal-cells-against-oxidative-stress-and-restores-rat-retinal-physiological-function-from-light-exposed-damage
#13
Fengxia Yan, Hai-Tao Wang, Yang Gao, Jiang-Ping Xu, Wenhua Zheng
Oxidative stress plays a key role in the pathogenesis of age-related macular degeneration (AMD), a leading cause of severe visual loss and blindness in the aging population which lacks any effective treatments currently. In this study, artemisinin, a well-known anti-malarial drug was found to suppress hydrogen peroxide (H2O2)-induced cell death in retinal neuronal RGC-5 cells. Artemisinin, in the therapeutically relevant dosage, concentration-dependently attenuated the accumulation of intracellular reactive oxygen species (ROS), increased mitochondrial mitochondrial membrane potential and decreased cell apoptosis in RGC-5 cells induced by H2O2...
April 27, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28441791/selective-toxicity-of-non-polar-bioactive-compounds-of-persian-gulf-sea-squirt-phallusia-nigra-on-skin-mitochondria-isolated-from-rat-model-of-melanoma
#14
Yalda Arast, Nina Seyed Razi, Enayatollah Seydi, Parvaneh Naserzadeh, Melika Nazemi, Jalal Pourahmad
Background: Skin cancer is the most prevalent cancer and one of the major causes of mortality worldwide. Marin animals have attracted much attention in recent years as useful substances having application in medicine. It was shown that Phallusia nigra (P. nigra) known as sea squirt could play an important role in cancer therapy. Methods: This study was designed to figure out the probable selective toxicity of n-hexane, diethyl ether, methanolic and aqueous extracts of P. nigra on cancerous mitochondria isolated from the skin of melanoma induced rats...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28441462/transcriptomic-profiling-of-a-chicken-lung-epithelial-cell-line-clec213-reveals-a-mitochondrial-respiratory-chain-activity-boost-during-influenza-virus-infection
#15
Léa Meyer, Olivier Leymarie, Christophe Chevalier, Evelyne Esnault, Marco Moroldo, Bruno Da Costa, Sonia Georgeault, Philippe Roingeard, Bernard Delmas, Pascale Quéré, Ronan Le Goffic
Avian Influenza virus (AIV) is a major concern for the global poultry industry. Since 2012, several countries have reported AIV outbreaks among domestic poultry. These outbreaks had tremendous impact on poultry production and socio-economic repercussion on farmers. In addition, the constant emergence of highly pathogenic AIV also poses a significant risk to human health. In this study, we used a chicken lung epithelial cell line (CLEC213) to gain a better understanding of the molecular consequences of low pathogenic AIV infection in their natural host...
2017: PloS One
https://www.readbyqxmd.com/read/28440433/effective-cytotoxic-activity-of-osw-1-on-colon-cancer-by-inducing-apoptosis-in%C3%A2-vitro-and-in%C3%A2-vivo
#16
Yanhong Zhang, Fengqi Fang, Kai Fan, Yanli Zhang, Jie Zhang, Huishu Guo, Peiyao Yu, Jianmei Ma
As a natural compound, Ornithogalum caudatum Ait is primarily used as an anti-inflammatory and antitumor agent in Chinese folk medicine. In 1992, OSW-1 was isolated from this compound, which is a new member of cholestane saponin family. In numerous recent studies, OSW-1 has been shown to have powerful cytotoxic anticancer effects against various malignant cells. However, the therapeutic efficacy of OSW-1 on colon cancer and the underlying mechanism are not understood. To explore the mechanism underlying OSW-1 in antitumor therapy, a therapeutic function analysis of OSW-1 on colon cancer was performed in vitro and in vivo...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28438533/association-of-mir-145-with-statin-induced-skeletal-muscle-toxicity-in-human-rhabdomyosarcoma-rd-cells
#17
Shun Saito, Takeo Nakanishi, Yuma Shirasaki, Miki Nakajima, Ikumi Tamai
Skeletal muscle toxicity including rhabdomyolysis in severe case is a major side effect of LDL cholesterol-lowering statin drugs. We, therefore, aimed to explore microRNA (miRNA) expression to understand molecular mechanism of statin-induced toxicity. miRNA expression profiling assay for cerivastatin (1 μM for 48 hr)-treated RD cells showed more than two-fold decrease in 26 miRNA expressions with miR-145 being down-regulated prominently. When RD cells were treated with cerivastatin at 10 μM for 36 hr, mitochondrial dysfunction was observed in 49...
April 21, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28423950/hepatoprotective-and-free-radical-scavenging-actions-of-quercetin-nanoparticles-on-a%C3%AF-atoxin-b1-induced-liver-damage-in-vitro-in-vivo-studies
#18
Aziz Eftekhari, Elham Ahmadian, Vahid Panahi-Azar, Hedayat Hosseini, Mahnaz Tabibiazar, Solmaz Maleki Dizaj
The objective of present study was in vitro and in vivo evaluation of hepatoprotective and antioxidant activity of Quercetin nanoparticles (Q NPs) against toxicity induced by aflatoxin B1. The Q NPs were prepared using precipitation method. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. The NPs were characterized in terms of size and morphology using dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The level of parameters, such as cell death, ROS formation, lipid peroxidation, mitochondrial membrane potential and cellular glutathione (GSH) content, in the aflatoxin B1-treated and non-treated hepatocytes were determined and the mentioned markers were assessed in the presence of Q NPs...
April 20, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28423723/honokiol-an-activator-of-sirtuin-3-sirt3-preserves-mitochondria-and-protects-the-heart-from-doxorubicin-induced-cardiomyopathy-in-mice
#19
Vinodkumar B Pillai, Abhinav Kanwal, Yong Hu Fang, Willard W Sharp, Sadhana Samant, Jack Arbiser, Mahesh P Gupta
Doxorubicin is the chemotherapeutic drug of choice for a wide variety of cancers, and cardiotoxicity is one of the major side effects of doxorubicin treatment. One of the main cellular targets of doxorubicin in the heart is mitochondria. Mitochondrial sirtuin, SIRT3 has been shown to protect against doxorubicin-induced cardiotoxicity. We have recently identified honokiol (HKL) as an activator of SIRT3, which protects the heart from developing pressure overload hypertrophy. Here, we show that HKL-mediated activation of SIRT3 also protects the heart from doxorubicin-induced cardiac damage without compromising the tumor killing potential of doxorubicin...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421296/metabolite-signatures-of-doxorubicin-induced-toxicity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#20
Umesh Chaudhari, James K Ellis, Vilas Wagh, Harshal Nemade, Jürgen Hescheler, Hector C Keun, Agapios Sachinidis
Drug-induced off-target cardiotoxicity, particularly following anti-cancer therapy, is a major concern in new drug discovery and development. To ensure patient safety and efficient pharmaceutical drug development, there is an urgent need to develop more predictive cell model systems and distinct toxicity signatures. In this study, we applied our previously proposed repeated exposure toxicity methodology and performed (1)H NMR spectroscopy-based extracellular metabolic profiling in culture medium of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer agent...
April 18, 2017: Amino Acids
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