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Drug induced mitochondrial toxicity

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https://www.readbyqxmd.com/read/29132812/the-antitumor-effect-of-folic-acid-conjugated-auricularia-auricular-polysaccharide-cisplatin-complex-on-cervical-carcinoma-cells-in-nude-mice
#1
Junqiang Qiu, Hua Zhang, Zhenyu Wang, Didi Liu, Shumin Liu, Wei Han, Joe M Regenstein, Lin Geng
A tumor-targeted, folic acid (FA) conjugated-Auricularia auricular polysaccharide (AAP) -cis-diaminedichloroplatinum (CDDP) complex (FA-AAP-CDDP) was used for cervical carcinoma chemotherapy. The drug delivery system was able to enhance the antitumor potency of CDDP, and to reduce the toxic side effects of CDDP. The kidney of mice treated by FA-AAP-CDDP complex had higher superoxide dismutase, catalase, and glutathione peroxidase activities, and lower malondialdehyde. FA-AAP-CDDP complex could induce more interleukin-2, interleukin-4, and interferon-γ in mice...
November 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29128607/effects-of-a-new-antiprotozoal-drug-n-n-diphenyl-4-methoxy-benzamidine-on-energy-linked-functions-of-rat-liver-mitochondria
#2
Lyvia Lintzmaier Petiz, Amanda do Rocio Andrade Pires, Aurea Echevarria, Cláudio Eduardo Rodrigues-Santos, Maria Eliane Merlin Rocha, Alexandra Acco, Silvia Maria Suter Correia Cadena
Amidines are chemically characterized by the presence of two nitrogen atoms that bind to the same carbon atom in its structure. Several biological activities have been ascribed to these compounds. Pentamidine, an aromatic diamidine, is effective in the treatment against Pneumocystis carinii and leishmaniasis, but it can also have severe side effects. New amidine derivatives have been synthesized, among them N,N'-diphenyl-4-methoxy-benzamidine (methoxyamidine), which is effective against Leishmania amazonensis (LD50 = 20 μM) and Trypanosoma cruzi (LD50 = 59 nM)...
November 9, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29123480/impairment-of-mitochondrial-biogenesis-and-dynamics-involved-in-isoniazid-induced-apoptosis-of-hepg2-cells-was-alleviated-by-p38-mapk-pathway
#3
Tianguang Zhang, Takashi Ikejima, Lizhong Li, Ruiqin Wu, Xiaoyan Yuan, Jun Zhao, Yimei Wang, Shuangqing Peng
Isoniazid (INH), a widely used first-line antitubercular drug, has been noted to be associated with hepatotoxicity. In spite of extensive researches over many decades, the mechanism of INH-induced hepatotoxicity still remains poorly understood. Recently, mitochondrial toxicity has been emerging as a new paradigm for INH-induced hepatotoxicity. In this study, we showed that INH impaired mitochondrial biogenesis and dynamics in human hepatocarcinoma HepG2 cells. INH reduced mitochondrial membrane potential (MMP) and induced mitochondria swelling...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29115483/hepatocellular-toxicity-of-oxalicumone-a-via-oxidative-stress-injury-and-mitochondrial-dysfunction-in-healthy-human-liver-cells
#4
Si Shi, Limei Yao, Kunbin Guo, Xiangyu Wang, Qi Wang, Weirong Li
The marine‑derived oxalicumone A (POA) has been demonstrated as a potent anti‑tumor bioactive agent for a variety of human carcinoma, but to the best of our knowledge, remains to be evaluated in healthy liver cells. As many drugs distribute preferentially in the liver, the present study aimed to investigate the effects of POA on apoptosis, oxidative stress and mitochondrial function in L‑02 healthy liver cells. A Cell‑Counting kit‑8 assay demonstrated that POA inhibits the proliferation of L‑02 cells in a dose‑ and time‑dependent manner...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29109483/safety-of-nonporous-silica-nanoparticles-in-human-corneal-endothelial-cells
#5
Ja-Yeon Kim, Joo-Hee Park, Martha Kim, Hyejoong Jeong, Jinkee Hong, Roy S Chuck, Choul Yong Park
Nonporous silica nanoparticles (SiNPs) are promising drug carrier platforms for intraocular drug delivery. In this study, we investigated the safety of three different sizes of SiNPs (50, 100, and 150 nm) in a human corneal endothelial cell (HCEC) line, B4G12. The HCECs were exposed to different concentrations (0, 25, 50, and 100 µg/ml) of three sizes of SiNPs for up to 48 h. Cellular viability, autophagy, lactate dehydrogenase (LDH) assay, and mammalian target of rapamycin (mTOR) pathway activation were evaluated...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29107685/toxicity-and-structure-activity-relationship-sar-of-%C3%AE-%C3%AE-dehydroamino-acids-against-human-cancer-cell-lines
#6
Romeu A Videira, Paula B Andrade, Luís S Monteiro, Patrícia Valentão, Paula M T Ferreira, David M Pereira
A library of N-protected dehydroamino acids, namely dehydroalanine, dehydroaminobutyric acid and dehydrophenylalanine derivatives, was screened in three human cancer cell lines [(lung (A549), gastric (AGS) and neuroblastoma (SH-SY5Y)] in order to characterize their toxicological profile and identify new molecules with potential anticancer activity. Results showed N-protected dehydrophenylalanine and dehydroaminobutyric acid derivatives have no or low toxicity for all tested cell lines. The N-protected dehydroalanines exhibit significant toxic effects and the AGS and SH-SY5Y cells were significantly more vulnerable than A549 cells...
October 28, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29105555/toxicity-of-new-synthetic-amphetamine-drug-mephedrone-on-rat-heart-mitochondria-a-warning-for-its-abuse
#7
Parvaneh Naserzadeh, Farzaneh Jokar, Farzaneh Vafaei, Enayatollah Seydi, Jalal Pourahmad
1. Mephedrone, a new and popular amphetamine drug, is widely abused and is still legal in some parts around the world. Little data on mechanisms involved in mephedrone induced cardiotoxicity are available. 2. Therefore, we decided to explain the mechanisms of mephedrone cardiotoxicity by using mitochondria isolated from rat heart. The isolated heart mitochondria were incubated with different concentrations of mephedrone (5, 10 and 20 µM). 3. Results showed that mephedrone induced mitochondrial dysfunction via an increase in mitochondrial reactive oxygen species (ROS) production, MMP collapse, mitochondrial swelling and damage in the mitochondrial outer membrane (MOM) which is associated with the cytochrome c release...
November 6, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29101309/biochemical-targets-of-drugs-mitigating-oxidative-stress-via-redox-independent-mechanisms
#8
REVIEW
Bernd Gesslbauer, Valery Bochkov
Acute or chronic oxidative stress plays an important role in many pathologies. Two opposite approaches are typically used to prevent the damage induced by reactive oxygen and nitrogen species (RONS), namely treatment either with antioxidants or with weak oxidants that up-regulate endogenous antioxidant mechanisms. This review discusses options for the third pharmacological approach, namely amelioration of oxidative stress by 'redox-inert' compounds, which do not inactivate RONS but either inhibit the basic mechanisms leading to their formation (i...
November 3, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29097305/folate-acid-cyclodextrin-docetaxel-induces-apoptosis-in-kb-cells-via-the-intrinsic-mitochondrial-pathway-and-displays-antitumor-activity-in-vivo
#9
Jin Tao, Jiaojiao Xu, Fangcheng Chen, Beihua Xu, Jianqing Gao, Ying Hu
Docetaxel (DTX) is an antitumor therapeutic drug limited by solubility and selective delivery tissues. We previously prepared DTX/folate acid-Cyclodextrin (FA-CD) inclusion complexes that target folate receptors of tumor cells and showed that these complexes inhibited cancer cell proliferation by inducing apoptosis. Here we further determined the antitumor effect and apoptotic mechanism of DTX/FA-CD. DTX/FA-CD induced reactive oxygen species-mediated mitochondrial apoptosis in KB cells. DTX/FA-CD led to apoptosis accompanied with the repression of mitochondrial membrane potential and glutathione and overexpression of reactive oxygen species and catalase...
October 31, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29095935/beyond-the-polymerase-%C3%AE-theory-production-of-ros-as-a-mode-of-nrti-induced-mitochondrial-toxicity
#10
Reuben L Smith, Josephine M E Tan, Martijs J Jonker, Aldo Jongejan, Thomas Buissink, Steve Veldhuijzen, Antoine H C van Kampen, Stanley Brul, Hans van der Spek
Use of some HIV-1 nucleoside reverse transcriptase inhibitors (NRTI) is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to specific NRTIs has predominantly been assigned to mitochondrial polymerase-γ inhibition by NRTIs. However, an increasing amount of data suggests that this is not the sole mechanism. Many NRTI induced adverse events have been linked to the incurrence of oxidative stress, although the causality of events leading to reactive oxygen species (ROS) production and their role in toxicity is unclear...
2017: PloS One
https://www.readbyqxmd.com/read/29094594/nonsteroidal-anti-inflammatory-drug-induced-leaky-gut-modeled-using-polarized-monolayers-of-primary-human-intestinal-epithelial-cells
#11
Aadra P Bhatt, Dulan B Gunasekara, Jennifer Speer, Mark I Reed, Alexis N Peña, Bentley R Midkiff, Scott T Magness, Scott J Bultman, Nancy L Allbritton, Matthew R Redinbo
The intestinal epithelium provides a critical barrier that separates the gut microbiota from host tissues. Nonsteroidal anti-inflammatory drugs (NSAIDs) are efficacious analgesics and antipyretics and are among the most frequently used drugs worldwide. In addition to gastric damage, NSAIDs are toxic to the intestinal epithelium, causing erosions, perforations, and longitudinal ulcers in the gut. Here, we use a unique in vitro human primary small intestinal cell monolayer system to pinpoint the intestinal consequences of NSAID treatment...
November 10, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29090725/arginine-modification-of-lycosin-i-to-improve-inhibitory-activity-against-cancer-cells
#12
Peng Zhang, Jing Ma, Yujie Yan, Bo Chen, Bobo Liu, Cui Jian, Baode Zhu, Songping Liang, Youlin Zeng, Zhonghua Liu
Lycosin-I is a linear amphipathic α-helical anticancer peptide (ACP) extracted from the spider Lycosa singoriensis, which can activate the mitochondrial death pathway to induce apoptosis in tumor cells and up-regulate p27 to inhibit cell proliferation. However, the applicability of lycosin-I as a novel anticancer drug is limited by its low cellular entry and efficacy in solid tumors. Amino acid substitution presents an effective and modest strategy to improve the anticancer activity and bioavailability of ACPs...
November 15, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29082486/cell-based-high-content-analysis-of-cell-proliferation-and-apoptosis
#13
Bhaskar S Mandavilli, Michelle Yan, Scott Clarke
High content imaging-based cell cycle analysis allows multiplexing of various parameters including DNA content, DNA synthesis, cell proliferation, and other cell cycle markers such as phosho-histone H3. 5'-Ethynyl-2'-deoxyuridine (EdU) incorporation is a thymidine analog that provides a sensitive method for the detection of DNA synthesis in proliferating cells that is a more convenient method than the traditional BrdU detection by antibody. Caspase 3 is activated in programmed cell death induced by both intrinsic (mitochondrial) and extrinsic factors (death ligand)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29082485/tools-to-measure-cell-health-and-cytotoxicity-using-high-content-imaging-and-analysis
#14
Bhaskar S Mandavilli, Robert J Aggeler, Kevin M Chambers
High content screening (HCS)-based multiparametric measurements are very useful in early toxicity testing and safety assessment during drug development, and useful in evaluating the impact from new food supplements and environmental toxicants. Mitochondrial membrane potential, plasma membrane permeability, oxidative stress, phosphoplipidosis, and steatosis are a few of the important markers routinely studied for the assessment of drug-induced liver injury and toxicity. Mitochondrial dysfunction leads to oxidative stress and cell death...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29074620/the-natural-product-mensacarcin-induces-mitochondrial-toxicity-and-apoptosis-in-melanoma-cells
#15
Birte Plitzko, Elizabeth N Kaweesa, Sandra Loesgen
Mensacarcin is a highly oxygenated polyketide that was first isolated from soil-dwelling Streptomyces bacteria. It exhibits potent cytostatic properties (GI50: 0.2 μM) in almost all cell lines of the National Cancer Institute (NCI)-60 cell line screen and relatively selective cytotoxicity against melanoma cells. Moreover, its low COMPARE correlations with known standard antitumor agents indicate a unique mechanism of action. Effective therapies for managing melanoma are limited, so we sought to investigate mensacarcin's unique cytostatic and cytotoxic effects and its mode of action...
October 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29074412/molecular-mechanism-of-doxorubicin-induced-cardiomyopathy-an-update
#16
REVIEW
Kaviyarasi Renu, Abilash V G, Tirupathi Pichiah P B, Sankarganesh Arunachalam
Doxorubicin is utilized for anti-neoplastic treatment for several decades. The utility of this drug is limited due to its side effects. Generally, doxorubicin toxicity is originated from the myocardium and then other organs are also ruined. The mechanism of doxorubicin is intercalated with the DNA and inhibits topoisomerase 2. There are various signalling mechanisms involved in doxorubicin cardiotoxicity. First and foremost, the doxorubicin-induced cardiotoxicity is due to oxidative stress. Cardiac mitochondrial damage is supposed after few hours following the revelation of doxorubicin...
October 23, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29072336/mechanisms-of-toxicity-associated-with-six-tyrosine-kinase-inhibitors-in-human-hepatocyte-cell-lines
#17
Cécile Mingard, Franziska Paech, Jamal Bouitbir, Stephan Krähenbühl
Tyrosine kinase inhibitors have revolutionized the treatment of certain cancers. They are usually well tolerated, but can cause adverse reactions including liver injury. Currently, mechanisms of hepatotoxicity associated with tyrosine kinase inhibitors are only partially clarified. We therefore aimed at investigating the toxicity of regorafenib, sorafenib, ponatinib, crizotinib, dasatinib and pazopanib on HepG2 and partially on HepaRG cells. Regorafenib and sorafenib strongly inhibited oxidative metabolism (measured by the Seahorse-XF24 analyzer) and glycolysis, decreased the mitochondrial membrane potential and induced apoptosis and/or necrosis of HepG2 cells at concentrations similar to steady-state plasma concentrations in humans...
October 26, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29069746/wx-132-18b-a-novel-microtubule-inhibitor-exhibits-promising-anti-tumor-effects
#18
Fang Guan, Rui Ding, Qi Zhang, Wei Chen, Feifei Li, Long Long, Wei Li, Linna Li, Dexuan Yang, Lan Xie, Shoujun Yuan, Lili Wang
Cancer drug researchers have been seeking microtubule-inhibiting agents (MIAs) with higher bioactivity and lower toxicity than currently marketed drugs. WX-132-18B, a novel structural compound synthesized at our institute, specifically bound to the colchicine-binding site on tubulin rather than the vinblastine site, and concentration-dependently reduced microtubule content via depolymerization. It exhibited the same cellular phenotypic profiles as the classic MIAs (colchicine, vincristine, and taxol), including inducing cell cycle arrest at the G2/M phase, triggering tumor cell apoptosis, promoting nuclear membrane permeability, reducing mitochondrial membrane potential, and disrupting the redox system balance...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29063196/a-newly-synthesized-nickel-chelate-can-selectively-target-and-overcome-multidrug-resistance-in-cancer-through-redox-imbalance-both-in-vivo-and-in-vitro
#19
Kaushik Banerjee, Manas Kumar Biswas, Soumitra Kumar Choudhuri
Induction of undesired toxicity and emergence of multidrug resistance (MDR) are the major obstacles for cancer treatment. Moreover, aggressive cancers are less sensitive towards existing chemotherapeutics. Therefore, selective targeting of cancers without inducing undesired side effects and designing proper strategies to overcome MDR has utmost importance in modern chemotherapy. Previously we revealed the anticancer properties of some transition metal chelates of Schiff base, but the effectiveness of nickel complex is still unrevealed...
December 2017: Journal of Biological Inorganic Chemistry: JBIC
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
#20
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
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