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Mitochondrial toxicity

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https://www.readbyqxmd.com/read/29050305/calyxin-y-sensitizes-cisplatin-sensitive-and-resistant-hepatocellular-carcinoma-cells-to-cisplatin-through-apoptotic-and-autophagic-cell-death-via-scf-%C3%AE-trcp-mediated-eef2k-degradation
#1
Chao Zhang, Jian-Li Lei, Hao Zhang, Yuan-Zheng Xia, Pei Yu, Lei Yang, Ling-Yi Kong
The down-regulation of eukaryotic elongation factor-2 kinase (eEF2K) is associated with an enhancement in the sensitivity of malignant cells to chemotherapeutic agents. In this study, we found that the silencing of eEF2K enhanced cisplatin (CDDP)-induced cytotoxicity in CDDP-sensitive (HepG2) and resistant (HepG2/CDDP) cells. Calyxin Y, a unique chalcone diarylheptanoid adduct, down-regulated eEF2K by promoting Skp1-Cul1-F-box protein (SCF) β-transducin repeat-containing protein (βTrCP)-mediated protein degradation and synergistically enhanced the cytotoxicity of CDDP...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050217/triterpenoids-from-aglaia-abbreviata-exert-cytotoxicity-and-multidrug-resistant-reversal-effect-in-mcf-7-adm-cells-via-reactive-oxygen-species-induction-and-p-glycoprotein-inhibition
#2
Juan Cen, Beibei Zheng, Rubing Bai, Li Zhang, Feng Zhang, Xia Zhang
Triterpenoids from the Aglaia have been shown cytotoxicity on a broad spectrum of human tumor cells. In the present study, we extracted triterpenoids AA-5 (1) and AA-6 (2) from stems of Aglaia abbreviata, and studied their cytotoxicity in multidrug resistant (MDR) MCF-7/ADM cells. After 48 h treatment, AA-5 (1) and AA-6 (2) significantly increased mitochondrial-mediated apoptosis by enhancing reactive oxygen species (ROS) with depressed mitochondrial membrane potential and caspase-9 activities. The drug efflux transporter P-glycoprotein (P-gp) and the intracellular antioxidant systems, involving Glutathione S-Transferase π, Glutathione and heme oxygenase-1, were also inhibited via the ROS-depressed Akt/NF-E2-related factor 2 pathway...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049944/bioaccumulation-and-effects-of-novel-chlorinated-polyfluorinated-ether-sulfonate-in-freshwater-alga-scenedesmus-obliquus
#3
Wei Liu, Jingwen Li, Lichen Gao, Zhou Zhang, Jing Zhao, Xin He, Xin Zhang
Chlorinated polyfluorinated ether sulfonate (Cl-PFESA) is a novel alternative compound for perfluorooctane sulfonate (PFOS), with its environmental risk not well known. The bioaccumulation and toxic effects of Cl-PFESA in the freshwater alga is crucial for the understanding of its potential hazards to the aquatic environment. Scenedesmus obliquus was exposed to Cl-PFESA at ng L(-1) to mg L(-1), with the exposure regime beginning at the environmentally relevant level. The total log BAF of Cl-PFESA in S. obliquus was 4...
October 16, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29046394/recombinant-human-islet-amyloid-polypeptide-forms-shorter-fibrils-and-mediates-%C3%AE-cell-apoptosis-via-generation-of-oxidative-stress
#4
Richa Dubey, Pooja Minj, Nikita Malik, Devika M Sardesai, Shruti H Kulkarni, Jhankar D Acharya, Neel S Bhavesh, Shilpy Sharma, Ashutosh Kumar
Protein aggregation play an important role in many human diseases including Alzheimer's, Parkinson's and Type 2 diabetes mellitus (T2DM). Human islet amyloid polypeptide (hIAPP) forms amyloid plaques in pancreas of T2DM subjects that are involved in deteriorating islet function and in mediating β- cell apoptosis. However, the detailed mechanism of action, structure and nature of toxic hIAPP species responsible for this effect remains elusive till date mainly due to the high cost associated with the chemical synthesis of pure peptide required for these studies...
October 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29046140/amplification-of-arsenic-genotoxicity-by-tio2-nanoparticles-in-mammalian-cells-new-insights-from-physicochemical-interactions-and-mitochondria
#5
Xinan Wang, Yun Liu, Juan Wang, Yaguang Nie, Shaopeng Chen, Tom K Hei, Zhaoxiang Deng, Lijun Wu, Guoping Zhao, An Xu
Titanium dioxide nanoparticles (TiO2 NPs) have shown great adsorption capacity for arsenic (As); however, the potential impact of TiO2 NPs on the behavior and toxic responses of As remains largely unexplored. In the present study, we focused on the physicochemical interaction between TiO2 NPs and As(III) to clarify the underlying mechanisms involved in their synergistic genotoxic effect on mammalian cells. Our data showed that As(III) mainly interacted with TiO2 NPs by competitively occupying the sites of hydroxyl groups on the surface of TiO2 NP aggregates, resulting in more aggregation of TiO2 NPs...
October 18, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/29044755/epoxyazadiradione-purified-from-the-azadirachta-indica-seed-induced-mitochondrial-apoptosis-and-inhibition-of-nf%C3%AE%C2%BAb-nuclear-translocation-in-human-cervical-cancer-cells
#6
G Shilpa, J Renjitha, R Saranga, Francis K Sajin, Mangalam S Nair, Beena Joy, B S Sasidhar, S Priya
Epoxyazadiradione (EAD) is an important limonoid present in Neem (Azadirachta indica) plant. In the present study, we have purified EAD from Neem seed and studied its anticancer potential in human cervical cancer (HeLa) cells. Cell proliferation inhibition studies indicated that the GI50 value of EAD is 7.5 ± 0.0092 μM in HeLa cells, whereas up to 50 μM concentrations EAD did not affect the growth of normal H9C2 cells. The control drug cisplatin inhibited the growth of both HeLa and H9C2 cells with a GI50 value of 2...
October 18, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29043356/cationic-amphiphilic-zn-porphyrin-with-high-antifungal-photodynamic-potency
#7
Sara Moghnie, Artak Tovmasyan, James Craik, Ines Batinic-Haberle, Ludmil Benov
Photodynamic therapy (PDT) is a promising alternative approach particularly attractive for treatment of localized fungal infections. It is based on compounds, photosensitizers (PSs), which when excited with visible light, generate reactive species that ultimately cause cell death. Such species have short lifespans; as a consequence, efficiency and selectivity of the PDT treatment depend mainly on the properties of the PSs. This study is the first to explore the effect of cationic porphyrin-based photosensitizers on Saccharomyces cerevisiae, a member of the fungus kingdom...
October 18, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/29042293/development-of-novel-prediction-model-for-drug-induced-mitochondrial-toxicity-by-using-na%C3%A3-ve-bayes-classifier-method
#8
Hui Zhang, Peng Yu, Ji-Xia Ren, Xi-Bo Li, He-Li Wang, Lan Ding, Wei-Bao Kong
Mitochondrial dysfunction has been considered as an important contributing factor in the etiology of drug-induced organ toxicity, and even plays an important role in the pathogenesis of some diseases. The objective of this investigation was to develop a novel prediction model of drug-induced mitochondrial toxicity by using a naïve Bayes classifier. For comparison, the recursive partitioning classifier prediction model was also constructed. Among these methods, the prediction performance of naïve Bayes classifier established here showed best, which yielded average overall prediction accuracies for the internal 5-fold cross validation of the training set and external test set were 95 ± 0...
October 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29040955/protective-role-of-epigallocatechin-3-gallate-on-arsenic-induced-testicular-toxicity-in-swiss-albino-mice
#9
Pushpa Rani Guvvala, Janivara Parameswaraiah Ravindra, Chukkath Vijayan Rajani, Muniandy Sivaram, Sellappan Selvaraju
Arsenic, often referred to as the king of poisons is carcinogenic in humans and animals. It affects multiorgan systems including reproduction. The present study was undertaken to explore the protective role of green tea compound, epigallocatechin-3-gallate (EGCG) on arsenic induced testicular toxicity in Swiss albino mice. Thirty two adult male mice were randomly assigned to four groups (n=8). Group I served as control without test chemical. The group II received arsenic (200ppm) through drinking water, group III received only EGCG (20mg/kgb...
October 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29040533/hippocampal-phosphorylated-tau-induced-cognitive-decline-dendritic-spine-loss-and-mitochondrial-abnormalities-in-a-mouse-model-of-alzheimer-s-disease
#10
Ramesh Kandimalla, Maria Manczak, Xiangling Yin, Rui Wang, P Hemachandra Reddy
The purpose of our study was to understand the toxic effects of hippocampal phosphorylated tau in tau mice. Using rotarod and Morris Water Maze tests, immunoblotting & immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, measured protein levels of mitochondrial dynamics, MAP2, total & phosphorylated tau, and quantified dendritic spines and mitochondrial number and length in 12-month-old tau mice with P301L mutation. Mitochondrial function was assessed by measuring the levels of H2O2, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP...
October 12, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29037130/molecular-and-cellular-mechanisms-of-sporadic-alzheimer-s-disease-studies-on-rodent-models-in-vivo
#11
REVIEW
N V Gulyaeva, N V Bobkova, N G Kolosova, A N Samokhin, M Yu Stepanichev, N A Stefanova
In this review, recent data are presented on molecular and cellular mechanisms of pathogenesis of the most widespread (about 95%) sporadic forms of Alzheimer's disease obtained on in vivo rodent models. Although none of the available models can fully reproduce the human disease, several key molecular mechanisms (such as dysfunction of neurotransmitter systems, especially of the acetylcholinergic system, β-amyloid toxicity, oxidative stress, neuroinflammation, mitochondrial dysfunction, disturbances in neurotrophic systems) are confirmed with different models...
October 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29035293/identification-of-z-2-3-diphenylacrylonitrileas-anti-cancer-molecule-in-persian-gulf-sea-cucumber-holothuria-parva
#12
Salimeh Amidi, Zahra Hashemi, Abbasali Motallebi, Melika Nazemi, Hoda Farrokhpayam, Enayatollah Seydi, Jalal Pourahmad
Hepatocellular carcinoma (HCC), also named cancerous hepatoma, is the most common type of malignant neoplasia of the liver. In this research, we screened the Persian Gulf sea cucumber Holothuria parva (H. parva) methanolic sub-fractions for the possible existence of selective toxicity on liver mitochondria isolated from an animal model of HCC. Next, we purified the most active fraction. Thus the structure of the active molecule was identified. HCC was induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) protocol...
October 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29034965/role-of-serum-albumin-as-a-nanoparticulate-carrier-for-nose-to-brain-delivery-of-r-flurbiprofen-implications-for-the-treatment-of-alzheimer-s-disease
#13
Ling Rong Wong, Paul C Ho
OBJECTIVES: R-flurbiprofen (R-FP) was found to offer neuroprotective effects by inhibiting mitochondrial calcium overload induced by β-amyloid peptide toxicity in Alzheimer's disease (AD). However, poor brain penetration after oral administration posed a challenge to its further development for AD treatment. In this study, we investigated the potential of serum albumin as nanoparticulate carriers for nose-to-brain delivery of R-FP to improve its brain accumulation. METHODS: Mice were subjected to three treatment groups: (1) intranasal R-FP solution, (2) oral R-FP solution and (3) intranasal R-FP albumin nanoparticles...
October 16, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29034472/protective-effects-of-curcumin-against-aflatoxicosis-a-comprehensive-review
#14
REVIEW
Mohammad Mohajeri, Behzad Behnam, Arrigo F G Cicero, Amirhossein Sahebkar
Aflatoxicosis is a deleterious medical condition that results from aflatoxins (AFs) or ochratoxins (OTs). Contamination with these toxins exerts detrimental effects on the liver, kidneys, reproductive organs, and also on immunological and cardiovascular systems. Aflatoxicosis is closely associated with overproduction of reactive oxygen species (ROS) as key contributors to oxidative and nitrosative stress responses, and subsequent damages to lipids, proteins, RNA, and DNA. The main target organ for AF toxicity is the liver, where DNA adducts, degranulation of endoplasmic reticulum, increased hepatic lipid peroxide, GSH depletion, mitochondrial dysfunction, and reduction of enzymatic and non-enzymatic antioxidants are manifestations of aflatoxicosis...
October 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29033575/renal-safety-of-tenofovir-and-or-entecavir-in-patients-with-chronic-hbv-monoinfection
#15
REVIEW
Young-Mo Yang, Eun Joo Choi
BACKGROUND: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are recommended as the first-line therapy for chronic hepatitis B (CHB) due to their genetic barrier to resistance and effectiveness of virological suppression. TDF and ETV may cause renal toxicity through various mechanisms such as renal tubular injury, apoptosis, and mitochondrial toxicity. The aims of the current review were to assess the potential renal toxicity associated with the use of TDF and ETV in patients infected with chronic hepatitis B virus (HBV) and to provide clinical perspectives on these two agents in the treatment of CHB...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29031482/toxicologic-transport-properties-of-ncs-382-a-%C3%AE-hydroxybutyrate-ghb-receptor-ligand-in-neuronal-and-epithelial-cells-therapeutic-implications-for-ssadh-deficiency-a-gaba-metabolic-disorder
#16
K R Vogel, G R Ainslie, A McConnell, J-B Roullet, K M Gibson
We report the in vitro assessment of pharmacotoxicity for the high-affinity GHB receptor ligand, NCS-382, using neuronal stem cells derived from mice with a targeted deletion of the aldehyde dehydrogenase 5a1 gene (succinic semialdehyde dehydrogenase(SSADH)-deficient mice). These animals represent a phenocopy of the human disorder of GABA metabolism, SSADH deficiency, that metabolically features accumulation of both GABA and the GABA-analog γ-hydroxybutyric acid in conjunction with a nonspecific neurological phenotype...
October 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29031076/synthesis-and-evaluation-of-new-pyridyl-pyrazinyl-thiourea-derivatives-neuroprotection-against-amyloid-%C3%AE-induced-toxicity
#17
Jung-Eun Park, Ahmed Elkamhawy, Ahmed H E Hassan, Ae Nim Pae, Jiyoun Lee, Sora Paik, Beoung-Geon Park, Eun Joo Roh
Herein, we report synthesis and evaluation of new twenty six small molecules against β amyloid (Aβ)-induced opening of mitochondrial permeability transition pore (mPTP) using JC-1 assay which measures the change of mitochondrial membrane potential (ΔΨm). The neuroprotective effect of seventeen compounds against Aβ-induced mPTP opening was superior to that of the standard Cyclosporin A (CsA). Fifteen derivatives eliciting increased green to red fluorescence percentage less than 40.0% were evaluated for their impact on ATP production, cell viability and neuroprotection against Aβ-induced neuronal cell death...
September 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29031071/discovery-of-thienopyrrolotriazine-derivatives-to-protect-mitochondrial-function-against-a%C3%AE-induced-neurotoxicity
#18
TaeHun Kim, Woo Seung Son, Mohammad Neaz Morshed, Ashwini M Londhe, Seo Yun Jung, Jong-Hyun Park, Woo-Kyu Park, Sang Min Lim, Ki Duk Park, Sung Jin Cho, Kyu-Sung Jeong, Jiyoun Lee, Ae Nim Pae
Recovery of mitochondrial dysfunction has gained increasing attention as an alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the potential to serve as a drug target for the treatment of AD. In this study, we generated a structure-based pharmacophore model and virtually screened a commercial library, identifying SVH07 as a virtual hit, which contained a tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazine group...
September 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29031050/paraquat-affects-mitochondrial-bioenergetics-dopamine-system-expression-and-locomotor-activity-in-zebrafish-danio-rerio
#19
Xiao H Wang, Christopher L Souders, Yuan H Zhao, Christopher J Martyniuk
The dipyridyl herbicide paraquat induces oxidative stress in cells and is implicated in adult neurodegenerative diseases. However, less is known about paraquat toxicity in early stages of vertebrate development. To address this gap, zebrafish (Danio rerio) embryos were exposed to 1, 10 and 100 μM paraquat for 96 h. Paraquat did not induce significant mortality nor deformity in embryos and larvae, but it did accelerate time to hatch. To evaluate whether mitochondrial respiration was related to earlier hatch times, oxygen consumption rate was measured in whole embryos...
October 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/29030260/cyanidin-3-o-glucoside-promotes-the-biosynthesis-of-progesterone-through-the-protection-of-mitochondrial-function-in-pb-exposed-rat-leydig-cells
#20
Luona Wen, Xinwei Jiang, Jianxia Sun, Xia Li, Xusheng Li, Lingmin Tian, Ye Li, Weibin Bai
Cyanidin-3-O-glucoside (C3G) is an anthocyanin that has been reported to reduce the toxicity of heavy metals. In the present study, the protection effects of C3G on the biosynthesis of progesterone, the precursor of testosterone, against lead (Pb) in R2C rat Leydig cells were examined. Treatment of R2C cells with 100 μM Pb resulted in a significant decrease in progesterone production. After being cultured in a medium containing C3G and Pb, R2C cells exhibited an increase in progesterone concentration compared with the Pb treatment, as a result of up-regulation of the expression of the steroidogenic enzymes steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) and cytochrome P450 enzyme cholesterol side chain cleavage enzyme (CYP11A1)...
October 10, 2017: Food and Chemical Toxicology
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