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Mitochondrial toxicity

Yi Qian, Qing-Hua Han, Li-Chao Wang, Qiang Guo, Xu-Da Wang, Peng-Fei Tu, Ke-Wu Zeng, Hong Liang
ETHNOPHARMACOLOGICAL RELEVANCE: Albiziae Cortex (AC) is a widely used traditional medicine in China. It is possess various properties to treat insomnia, traumatic injuries, diuresis, sthenia, and confusion. Total saponins of Albiziae Cortex (TSAC) are the most abundant bioactive components of AC, which were reported to show significant anti-tumor effects in vivo and in vitro. But the underlying mechanism of TSAC remained to be revealed. AIM OF STUDY: In this study, we investigated the anti- hepatoma carcinoma effects and the potential mechanism of TSAC in vivo and in vitro...
April 12, 2018: Journal of Ethnopharmacology
Nathalie R Wingert, Marcelo D Arbo, Gabriela Göethel, Bárbara da Costa, Louise F Altknecht, Solange C Garcia, Martin Steppe
Degradation kinetics of oral anticoagulant rivaroxaban (RIV) was assessed in acid and alkaline media and while exposed to UVC radiation. Among all stress conditions tested, kinetic degradation process was better described by a zero-order model. A stability indicating method was validated for the analysis of the anticoagulant RIV in tablets by high-performance liquid chromatography. Robustness was evaluated with a two-level Plackett-Burman experimental design. The effect of acute exposition of the human hepatoblastoma HepG2 cell line to RIV stressed samples (100 and 500 µM) was assessed through in vitro toxicity tests...
April 12, 2018: Drug and Chemical Toxicology
Anthony E Lang, Alberto J Espay
The greatest unmet therapeutic need in Parkinson's disease is the development of treatment that slows the relentless progression of the neurodegenerative process. The concept of "disease modification" encompasses intervention types ranging from those designed to slow the underlying degeneration to treatments directed at regenerating or replacing lost neurons. To date all attempts to develop effective disease-modifying therapy have failed. Many reasons have been proposed for these failures including our rudimentary understanding of disease pathogenesis and the assumption that each targeted mechanisms of disease apply to most patients with the same clinical diagnosis...
April 11, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Annick Judenherc-HaouzI, Takashi Sonobe, Vikhyat S Bebarta, Philippe Haouzi
This study was aimed at determining the efficacy of epinephrine, followed by chest compressions, in producing a return of spontaneous circulation (ROSC) during cyanide (CN)- or hydrogen sulfide (H2 S)-induced toxic cardiac pulseless electrical activity (PEA) in the rat. Thirty-nine anesthetized rats were exposed to either intravenous KCN (n = 27) or H2 S solutions (n = 12), at a rate that led to a PEA within less than 10 min. In the group intoxicated by CN, 20 rats were mechanically ventilated and received either epinephrine (0...
April 11, 2018: Cardiovascular Toxicology
Sanghamitra Singh, Diti Chatterjee Bhowmick, Satyabrata Pany, Myungkuk Joe, Noor Zaghlula, Aleksandar M Jeremic
Misfolded toxic human islet amyloid polypeptide or amylin (hA) and plasma membrane-associated redox complex, NADPH oxidase (NOX), have been implicated in the islet β-cell demise associated with type-2 diabetes mellitus (T2DM). Studies show that hA accumulation is stressful to β-cells and that misfolding of human amylin evokes redox stress and activates mitogen activated protein (MAP) kinases, p38 MAPK and c-Jun N-terminal (JNK) kinase. However, the molecular link and causality between hA-evoked redox stress, NOX activity and MAP kinases signaling in pancreatic β-cells is incompletely understood...
April 5, 2018: Biochimica et Biophysica Acta
Marco Fiorillo, Maria Peiris-Pagès, Rosa Sanchez-Alvarez, Lucia Bartella, Leonardo Di Donna, Vincenza Dolce, Giovanni Sindona, Federica Sotgia, Anna Rita Cappello, Michael P Lisanti
Here, we show that a 2:1 mixture of Brutieridin and Melitidin, termed "BMF", has a statin-like properties, which blocks the action of the rate-limiting enzyme for mevalonate biosynthesis, namely HMGR (3-hydroxy-3-methylglutaryl-CoA-reductase). Moreover, our results indicate that BMF functionally inhibits several key characteristics of CSCs. More specifically, BMF effectively i) reduced ALDH activity, ii) blocked mammosphere formation and iii) inhibited the activation of CSC-associated signalling pathways (STAT1/3, Notch and Wnt/beta-catenin) targeting Rho-GDI-signalling...
April 4, 2018: Biochimica et Biophysica Acta
Marcos Caballero-Molada, María D Planes, Helena Benlloch, Sergio Atares, Miguel A Naranjo, Ramón Serrano
In eukaryotic cells amino acid biosynthesis is feedback inhibited by amino acids through inhibition of conserved protein kinase Gcn2. This decreases phosphorylation of initiation factor eIF2a resulting in general activation of translation but inhibition of translation of mRNA for transcription factor (TF) Gcn4 in yeast or ATF4 in mammals. These TFs are positive regulators of amino acid biosynthetic genes. As several enzymes of amino acid biosynthesis contain iron-sulfur clusters and iron excess is toxic, iron and amino acid homeostasis should be coordinated...
April 6, 2018: Biochemical Journal
Yue Ying, Yue-Kai Hu, Jia-Lin Jin, Ji-Ming Zhang, Wen-Hong Zhang, Yu-Xian Huang
BACKGROUND: Current treatment options for chronic hepatitis B (CHB) are pegylated interferon alpha and nucleoside analogues (NAs). NAs have relatively fewer side effects than interferon alpha, and generally well tolerated. Previously 12.9% of patients on telbivudine treatment were reported to develop severe elevation of serum creatine phosphokinase (CPK) levels, but related clinical disease, like lactic acidosis (LA) and rhabdomyolysis (RM) were rare. The pathophysiology may be mitochondrial toxicity, for the NAs inhibit not only hepatitis B virus (HBV) polymerase, but also the host mitochondrial DNA polymerase γ...
April 6, 2018: BMC Gastroenterology
Derek G Bolser, David A Dreier, Erchao Li, Kevin J Kroll, Christopher J Martyniuk, Nancy D Denslow
Chemical contaminants present in the environment can affect mitochondrial bioenergetics in aquatic organisms and can have substantial effects on individual fitness. As early life stages of fish are particularly vulnerable to environmental contaminants, they are ideal models for examining the relationship between impaired mitochondrial bioenergetics (ATP-dependent respiration, basal oxidative respiration) and apical endpoints such as growth. Here, early life stages of the fathead minnow (Pimephales promelas), an ecologically relevant North American species, were used to investigate the relationship between mitochondrial bioenergetics and growth following perturbation with model mitochondrial toxicants 2,4-dinitrophenol and octylamine...
April 3, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
(no author information available yet)
Background: Recent evidence suggests that early neurodegenerative events associated with Alzheimer’s disease (AD) probably begin in the synaptic terminal, where it has been reported a large accumulation of β-amyloid protein (Aβ), one of the main factors described in the development of AD. We analyzed the influence of energy metabolism on the toxic effects of Aβ during aging on synaptosomes from neocortex and hippocampus of rats exposed to inhibitors of glycolytic and mitochondrial metabolism and we evaluated the protective effects of some antioxidant compounds...
2018: Revista Médica del Instituto Mexicano del Seguro Social
Yi Jin, Shizhu Chen, Nan Li, Yajing Liu, Gong Cheng, Cuimiao Zhang, Shuxiang Wang, Jinchao Zhang
When orthopedic joints coated by hydroxyapatite (HA) were implanted in the human body, they release wear debris into the surrounding tissues. The generation and accumulation of wear particles will induce aseptic loosening. However, the potential bioeffect and mechanism of HA-coated orthopedic implants on bone cells are poorly understood. In this study, defect-related luminescent bur-like hydroxyapatite (BHA) microspheres with the average diameter of 7-9 μm which are comparable to that of the wear-debris particles from aseptically loosened HA implants or HA debris have been synthesized by hydrothermal synthesis and the MC3T3-E1 cells were set as a cells model to study the potential bioeffect and mechanism of BHA microspheres...
March 30, 2018: Science China. Life Sciences
Feng Xu, Man Luo, Lulu He, Yuan Cao, Wen Li, Songmin Ying, Zhihua Chen, Huahao Shen
BACKGROUND/AIMS: Necroptosis, a form of programmed necrosis, is involved in the pathologic process of several kinds of pulmonary diseases. However, the role of necroptosis in particulate matter (PM)-induced pulmonary injury remains unclear. The objective of this study is to investigate the involvement of necroptosis in the pathogenesis of PM-induced toxic effects in pulmonary inflammation and mucus hyperproduction, both in vitro and in vivo. METHODS: PM was administered into human bronchial epithelial (HBE) cells or mouse airways, and the inflammatory response and mucus production were assessed...
March 29, 2018: Cellular Physiology and Biochemistry
Jun Yang, Linna Li, Chengwang Xu, Dexuan Yang, Shanshan Wang, Shoujun Yuan
A novel small molecular compound, 4‑ethyl‑8‑fluoro‑hydroxy‑9‑methoxy‑11‑methyl‑1,12‑dihydro‑4H‑2‑oxa‑6,12a‑diaza‑dibenzo[b,h]fluorene‑3,13‑dione (CT‑1042) exhibits potent antitumor activity against many tumor cells in vitro. However, the effects and underlying mechanisms of CT‑1042 in non‑small cell lung cancer (NSCLC) remain unclear. The present study was designed to determine the anticancer properties and underlying molecular mechanisms of CT‑1042 in NCI‑H460 NSCLC cells...
April 4, 2018: Oncology Reports
Chang-Ching Lin, Miao-Chia Lo, Rebecca R Moody, Nicholas O Stevers, Samantha L Tinsley, Duxin Sun
Targeting cancer stem cells (CSCs) is a key strategy to prevent cancers from developing drug resistance and metastasis. Mitochondria have been reported to be a vulnerability of CSCs by multiple studies. Here, we report that doxycycline, functioning as an inhibitor of mitochondrial biogenesis, can effectively target breast cancer stem cells (BCSCs). Our results revealed that doxycycline significantly decreased the frequency of aldehyde dehydrogenase‑positive (ALDH+) BCSCs as well as mammosphere formation efficiency in HER2+ and triple‑negative breast cancer (TNBC) subtypes...
March 27, 2018: Oncology Reports
Ajesh P Thomas, L Palanikumar, M T Jeena, Kibeom Kim, Ja-Hyoung Ryu
Mitochondria-targeted cancer therapies have proven to be more effective than other similar non-targeting techniques, especially in photodynamic therapy (PDT). Indocyanine dye derivatives, particularly IR-780, are widely known for their PDT utility. However, poor water solubility, dark toxicity, and photobleaching are limiting factors for these dyes, which otherwise show promise based on their good absorption in the near-infrared (NIR) region and mitochondria targeting ability. Herein, we introduce an indocyanine derivative ( IR-Pyr ) that is highly water soluble, exhibiting higher mitochondrial targetability and better photostability than IR-780...
December 1, 2017: Chemical Science
Kalaivani Thiagarajan, Naisarg Gamit, Saurabh Mandal, Dhanoop Manikoth Ayyathan, Rajasekaran Chandrasekaran
Methylmercury (MeHg), an organometallic contaminant is a well spotted cause for a series of disorders, especially in the central nervous system. As there is no proper treatment, Selinum vaginatum (Edgew) C. B. Clarke, a traditional medicinal plant, is taken in the present study for assessing its neuroprotective effect against MeHg induced toxicity using rat brain mitochondrial fractions. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide dye (MTT) assay indicated that there was a reduction in the mitochondrial viability in MeHg treated sample and IC50 value recorded was 2...
March 2018: Pakistan Journal of Pharmaceutical Sciences
Zhen Li, Qixian Chen, Yan Qi, Zhihao Liu, Tangna Hao, Xiaoxin Sun, Mingxi Qiao, Xiaodong Ma, Ting Xu, Xiuli Zhao, Chunrong Yang, Dawei Chen
A multifunctional nanoparticulate system composed of methoxy poly(ethylene glycol)-poly(L-histidine)-d-α-Vitamin E succinate (MPEG-PLH-VES) copolymers for encapsulation of doxorubicin (DOX) was elaborated with the aim of circumventing the multidrug resistance (MDR) in breast cancer treatment. The MPEG-PLH-VES nanoparticles (NPs) were subsequently functionalized with biotin motif for targeted drug delivery. The MPEG-PLH-VES copolymer exert no obvious effect on the P-gp expression level of MCF-7/ADR but exhibited a significant influence on the loss of mitochondrial membrane potential, the reduction of intracellular ATP level and the inhibition of P-gp ATPase activity of MCF-7/ADR cells...
April 4, 2018: Biomacromolecules
Yongxiang Wang, Jingcheng Wang, Hua Wang, Xinmin Feng, Yuping Tao, Jiandong Yang, Jun Cai
Spinal cord injury (SCI) is a serious trauma without efficient treatment currently. Necroptosis can be blocked post injury by special inhibitors. To investigate the effects of Necrosulfonamide (NSA) in the treatment of SCI, pathological condition, necroptosis related factors, mitochondrial function and ethological performance were detected. Pathological detection using HE staining was performed first. Reduced lesions and protected neurons were found in the injured spinal cord after treatment with NSA. No obvious toxicity on rat liver, kidney, heart and spleen was detected using HE staining...
March 31, 2018: World Neurosurgery
Hande Güçlü, Zeynep Banu Doganlar, Vuslat Pelitli Gürlü, Altan Özal, Ayten Dogan, Meryem Aysenur Turhan, Oguzhan Doganlar
Combination therapies of cisplatin with 5-FU (PF) are an effective solution and have been widely used for the treatment of various categories of cancer. including anal, gastrointestinal and oral cancer, as well as head and neck tumours. The effects of combined PF treatment on vital intracellular signalling pathways in nontargeted cells remain unclear. The aim of this study is to explain the possible mechanisms by which combined PF treatment results in retinal toxicity and to investigate the effects of PF on important vital signalling pathways in ARPE 19 retinal pigmented epithelial cells...
April 2, 2018: Cutaneous and Ocular Toxicology
Ke-Bin Huang, Feng-Yang Wang, Xiao-Ming Tang, Hai-Wen Feng, Zhen-Feng Chen, Yan-Cheng Liu, You-Nian Liu, Hong Liang
Agents induced both apoptosis and autophagic death can be effective chemotherapeutic drugs. In our present work, we synthesized two organometallic gold(III) complexes harbouring C^N ligands that structurally resemble THIQ, Cyc-Au-1 (AuL1Cl2, L1 = 3,4-dimethoxyphenethylamine) and Cyc-Au-2 (AuL2Cl2, L2 = methylenedioxyphenethylamine). In screening their in vitro activity, we found both gold complexes to exhibit lower toxicity, lower resistance factors and better anticancer activity than cisplatin. The organometallic gold(III) complexes accumulate in mitochondria and induce elevated ROS and an ER stress response through mitochondrial dysfunction...
April 2, 2018: Journal of Medicinal Chemistry
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