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Drug induced mitochondrial toxicity

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https://www.readbyqxmd.com/read/28733192/pharmacological-evaluation-of-phytochemicals-from-south-indian-black-turmeric-curcuma-caesia-roxb-to-target-cancer-apoptosis
#1
K S Mukunthan, R S Satyan, T N Patel
Curcuma caesia Roxb. (Black turmeric), a perennial herb of the family Zingiberaceae is indigenous to India. C. caesia is used as a spice, food preservative and coloring agent commonly in the Indian subcontinent. Functional parametric pharmacological evaluations like drug ability and toxicity profile of this endangered species is poorly documented. In our present study, among all the extracts of dried C. caesia rhizome viz- hexane, ethyl acetate, methanol and water tested for free radical scavenging capacity by total antioxidant activity (TAO) method, Hexane Rhizome Extract (HRE) wzs found to possess remarkable activity (1200mg ascorbic acid equivalent/100g)...
July 18, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28726777/humanin-g-hng-protects-age-related-macular-degeneration-amd-transmitochondrial-arpe-19-cybrids-from-mitochondrial-and-cellular-damage
#2
Sonali Nashine, Pinchas Cohen, Marilyn Chwa, Stephanie Lu, Anthony B Nesburn, Baruch D Kuppermann, M Cristina Kenney
Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28722244/risk-of-liver-decompensation-with-cumulative-use-of-mitochondrial-toxic-nucleoside-analogues-in-hiv-hepatitis-c-virus-coinfection
#3
Vincent Lo Re Rd, Bret Zeldow, Michael J Kallan, Janet P Tate, Dena M Carbonari, Sean Hennessy, Jay R Kostman, Joseph K Lim, Matthew Bidwell Goetz, Robert Gross, Amy C Justice, Jason A Roy
PURPOSE: Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death. METHODS: We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients...
July 19, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28705594/induction-of-abcg2-bcrp-restricts-the-distribution-of-zidovudine-to-the-fetal-brain-in-rats
#4
María Fernanda Filia, Timoteo Marchini, Juan Mauricio Minoia, Martín Ignacio Roma, Fernanda Teresa De Fino, Modesto Carlos Rubio, Guillermo J Copello, Pablo A Evelson, Roxana Noemí Peroni
Safety concerns for fetus development of zidovudine (AZT) administration as prophylaxis of vertical transmission of HIV persist. We evaluated the participation of the ATP-binding cassette efflux transporter ABCG2 in the penetration of AZT into the fetal brain and the relevance for drug safety. Oral daily doses of AZT (60mg/kg body weight) or its vehicle were administered between post gestational days 11 (E11) and 20 (E20) to Sprague-Dawley pregnant rats. At E21, animals received an intravenous bolus of 60mg AZT/kg body weight in the presence or absence of the ABCG2 inhibitor gefitinib (20mg/kg body weight, ip) and AZT in maternal plasma and fetal brain were measured by HPLC-UV...
July 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28690189/efavirenz-what-is-known-about-the-cellular-mechanisms-responsible-for-its-adverse-effects
#5
REVIEW
Nadezda Apostolova, Ana Blas-Garcia, Maria J Galindo, Juan V Esplugues
The HIV infection remains an important health problem worldwide. However, due to the efficacy of combined antiretroviral therapy (cART), it has ceased to be a mortal condition, becoming a chronic disease instead. Efavirenz, the most prescribed non-nucleoside analogue reverse transcriptase inhibitor (NNRTI), has been a key component of cART since its commercialization in 1998. Though still a drug of choice in many countries, its primacy has been challenged by the arrival of newer antiretroviral agents with better toxicity profiles and treatment adherence...
July 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28689965/ph-and-nir-light-responsive-magnetic-iron-oxide-nanoparticles-for-mitochondria-mediated-apoptotic-cell-death-induced-by-chemo-photothermal-therapy
#6
Yunok Oh, Jae-Young Je, Madhappan Santha Moorthy, Hansoo Seo, Won Ho Cho
Recently, various therapeutic strategies in anticancer drug development are focused to reduce adverse side effects and to enhance the therapeutic efficacy. Mostly, the iron oxide (Fe3O4) nanoparticles have widely been utilized as an efficient drug delivery system towing to their unique properties such as excellent magnetic behavior, considerably low toxicity, easy surface modification and high drug-loading efficacy. In the present study, we synthesized a multifunctional, DMSA coated, water soluble Fe3O4 nanoparticles (Fe3O4@DMSA/DOX) for an effective pH and NIR-light triggered delivery of anticancer drug (DOX) in cancer therapy...
July 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28689063/proanthocyanidins-from-uncaria-rhynchophylla-induced-apoptosis-in-mda-mb-231-breast-cancer-cells-while-enhancing-cytotoxic-effects-of-5-fluorouracil
#7
Xiao-Xin Chen, George Pak-Heng Leung, Zhang-Jin Zhang, Jian-Bo Xiao, Li-Xing Lao, Feng Feng, Judith Choi-Wo Mak, Ying Wang, Stephen Cho-Wing Sze, Kalin Yan-Bo Zhang
Breast cancer is the most frequently diagnosed cancer and cause of cancer death in women worldwide. Current treatments often result in systematic toxicity and drug resistance. Combinational use of non-toxic phytochemicals with chemotherapeutic agents to enhance the efficacy and reduce toxicity would be one promising approach. In this study, bioactive proanthocyanidins from Uncaria rhynchophylla (UPAs) were isolated and their anti-breast cancer effects alone and in combination with 5- fluorouracil (5-FU) were investigated in MDA-MB-231 breast cancer cells...
July 5, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28685843/oxidative-stress-management-in-the-hair-follicle-could-targeting-nrf2-counter-age-related-hair-disorders-and-beyond
#8
REVIEW
Laura Jadkauskaite, Pierre A Coulombe, Matthias Schäfer, Albena T Dinkova-Kostova, Ralf Paus, Iain S Haslam
Widespread expression of the transcription factor, nuclear factor (erythroid-derived 2)-like 2 (NRF2), which maintains redox homeostasis, has recently been identified in the hair follicle (HF). Small molecule activators of NRF2 may therefore be useful in the management of HF pathologies associated with redox imbalance, ranging from HF greying and HF ageing via androgenetic alopecia and alopecia areata to chemotherapy-induced hair loss. Indeed, NRF2 activation has been shown to prevent peroxide-induced hair growth inhibition...
July 7, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28684237/monoaminergic-toxicity-induced-by-cathinone-phthalimide-an-in-vitro-study
#9
Susan M Lantz, Hector Rosas-Hernandez, Elvis Cuevas, Bonnie Robinson, Kenner C Rice, William E Fantegrossi, Syed Z Imam, Merle G Paule, Syed F Ali
Bath salts, or synthetic cathinones, have cocaine-like or amphetamine-like properties and induce psychoactive effects via their capacity to modulate serotonin (5-HT) and dopamine (DA). Structurally distinct synthetic cathinones are continuously being generated to skirt existing drug laws. One example of these modified compounds is cathinone phthalimide (CP), which has already appeared on the global market. The lack of toxicological studies on the effects of CP on monoaminergic systems led to the development of the present study in order to generate an acute toxicity profile for CP, and to clarify whether it primarily affects both dopamine and serotonin, like the synthetic cathinones mephedrone and methylone, or primarily affects dopamine, like 3, 4-methylenedioxypyrovalerone (MDPV)...
July 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28680449/protective-effects-of-wogonin-against-alzheimer-s-disease-by-inhibition-of-amyloidogenic-pathway
#10
Ding-Siang Huang, Yu-Chen Yu, Chung-Hsin Wu, Jung-Yaw Lin
One of the pathogenic systems of Alzheimer's disease (AD) is the formation of β-amyloid plaques in the brains of patients, and amyloidogenic activity becomes one of the therapeutic targets. Here, we report wogonin, one of the major active constituting components in Scutellaria baicalensis, which has the neuroprotective effects on amyloid-β peptides- (Aβ-) induced toxicity. Oral wogonin treatment improved the performance of triple transgenic AD mice (h-APPswe, h-Tau P301L, and h-PS1 M146V) on the Morris water maze, Y-maze, and novel object recognition...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28664269/pro-apoptotic-cationic-host-defense-peptides-rich-in-lysine-or-arginine-to-reverse-drug-resistance-by-disrupting-tumor-cell-membrane
#11
Yuxuan Dai, Xingguang Cai, Wei Shi, Xinzhou Bi, Xin Su, Miaobo Pan, Huilan Li, Haiyan Lin, Wenlong Huang, Hai Qian
Host defense peptides have been demonstrated to exhibit prominent advantages in cancer therapy with selective binding ability toward tumor cells via electrostatic attractions, which can overcome the limitations of traditional chemotherapy drugs, such as toxicity on non-malignant cells and the emergence of drug resistance. In this work, we redesigned and constructed a series of cationic peptides by inserting hydrophobic residues into hydrophilic surface or replacing lysine (K) with arginine (R), based on the experience from the preliminary work of host defense peptide B1...
June 29, 2017: Amino Acids
https://www.readbyqxmd.com/read/28662902/the-use-of-electronic-neutral-penetrating-peptides-cyclosporin-a-to-deliver-pro-apoptotic-peptide-a-possibly-better-choice-than-positively-charged-tat
#12
Wei Gao, Xiucong Yang, Zhiqiang Lin, Bing He, Dong Mei, Dan Wang, Haoran Zhang, Hua Zhang, Wenbing Dai, Xueqing Wang, Qiang Zhang
Cell-penetrating peptides (CPPs) are increasingly important in transporting macromolecules across cell membranes, but their use remains confined to narrow clinical applications due to the systemic toxicity induced by their positive charges. Several newly discovered electronic neutral penetrating peptides are not attracting much attention because their penetrating capacity is normally far less powerful than cationic or amphiphilic CPPs. In this study, we found the electronic neutral cyclic peptide cyclosporin A (CsA) exhibited 5...
June 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28659801/hepatocellular-toxicity-associated-with-tyrosine-kinase-inhibitors-mitochondrial-damage-and-inhibition-of-glycolysis
#13
Franziska Paech, Jamal Bouitbir, Stephan Krähenbühl
Tyrosine kinase inhibitors (TKIs) are anticancer drugs with a lesser toxicity than classical chemotherapeutic agents but still with a narrow therapeutic window. While hepatotoxicity is known for most TKIs, underlying mechanisms remain mostly unclear. We therefore aimed at investigating mechanisms of hepatotoxicity for imatinib, sunitinib, lapatinib and erlotinib in vitro. We treated HepG2 cells, HepaRG cells and mouse liver mitochondria with TKIs (concentrations 1-100 μM) for different periods of time and assessed toxicity...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28655613/int131-increases-dendritic-arborization-and-protects-against-a%C3%AE-toxicity-by-inducing-mitochondrial-changes-in-hippocampal-neurons
#14
Juan A Godoy, Juan M Zolezzi, Nibaldo C Inestrosa
In previous studies, we have demonstrated the beneficial effects of classic PPARγ agonists on neuroprotection against Aβ oligomer neurotoxicity in a double transgenic mouse model of Alzheimer' disease (AD). INT-131, a novel, non-thiazolidinedione compound that belongs to a new family of drugs, selective PPARγ modulators (SPPARMs), has provided an emerging opportunity for the treatment of type 2 diabetes mellitus and metabolic syndrome. However, its role in the central nervous system has not been studied...
June 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28650379/tenofovir-induced-toxicity-in-renal-proximal-tubular-epithelial-cells-involvement-of-mitochondria
#15
Lara Milián, José E Peris, Patricia Gandía, Isabel Andújar, Luis Pallardó, Jose L Górriz, Ana Blas-García
OBJECTIVE: In-vivo studies suggest that mitochondria is involved in tenofovir (TFV)-induced renal toxicity, but the underlying mechanisms are still unclear. The aim of the present study was to assess the effects of TFV and its prodrug, TFV disoproxil fumarate, on mitochondrial function and cell survival/viability in a renal proximal tubular cell line. DESIGN AND METHODS: We evaluated parameters of cellular proliferation/survival (cell count, cell cycle, viability) and mitochondrial function (oxygen consumption, mitochondrial membrane potential, reactive oxygen species production) in NRK-52E cells...
July 31, 2017: AIDS
https://www.readbyqxmd.com/read/28647477/derivatives-of-alkyl-gallate-triphenylphosphonium-exhibit-antitumor-activity-in-a-syngeneic-murine-model-of-mammary-adenocarcinoma
#16
Liliana Peredo-Silva, Sebastián Fuentes-Retamal, Cristian Sandoval-Acuña, Mario Pavani, Juan D Maya, Vicente Castro-Castillo, Matías Madrid-Rojas, Solange Rebolledo, Ulrike Kemmerling, Eduardo Parra, Jorge Ferreira
We previously demonstrated that alkyl gallates coupled to triphenylphosphine have a selective and efficient antiproliferative effect by inducing mitochondrial uncoupling in vitro due to the increased mitochondrial transmembrane potential of tumor cells. Therefore, in this work, the in vivo antitumor activities of alkyl gallate triphenylphosphonium derivatives (TPP(+)C8, TPP(+)C10 and TPP(+)C12) were evaluated in a syngeneic murine model of breast cancer. We found that TPP(+)C10 increased the cytosolic ADP/ATP ratio and significantly increased the AMP levels in a concentration-dependent manner in TA3/Ha murine mammary adenocarcinoma cells...
August 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28645576/mechanisms-of-hepatocellular-toxicity-associated-with-new-psychoactive-synthetic-cathinones
#17
Dino Luethi, Matthias E Liechti, Stephan Krähenbühl
Synthetic cathinones are a new class of psychostimulant substances. Rarely, they can cause liver injury but associated mechanisms are not completely elucidated. In order to increase our knowledge about mechanisms of hepatotoxicity, we investigated the effect of five frequently used cathinones on two human cell lines. Bupropion was included as structurally related drug used therapeutically. In HepG2 cells, bupropion, MDPV, mephedrone and naphyrone depleted the cellular ATP content at lower concentrations (0...
July 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28627468/a-novel-chalcone-derivative-lqfm064-induces-breast-cancer-cells-death-via-p53-p21-kit-and-pdgfra
#18
Bruna Lannuce Silva Cabral, Artur Christian Garcia da Silva, Renato Ivan de Ávila, Alane Pereira Cortez, Rangel Magalhães Luzin, Luciano Morais Lião, Eric de Souza Gil, Gérman Sanz, Boniek G Vaz, José R Sabino, Ricardo Menegatti, Marize Campos Valadares
This study shows the design, synthesis and antitumoral potential evaluation of a novel chalcone-like compound, (E)-3- (3, 5-di-ter-butyl-4-hydroxyphenyl)-1- (4-hydroxy-3-methoxyphenyl) prop-2-en-1-one [LQFM064) (4)], against human breast adenocarcinoma MCF7 cells. Some toxicological parameters were also investigated. LQFM064) (4) exhibited cytotoxic activity against MCF7 cells (IC50=21μM), in a concentration dependent-manner, and triggered significant changes in cell morphology and biochemical/molecular parameters, which are suggestive of an apoptosis inductor...
June 13, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28615926/mechanistic-modelling-of-drug-induced-liver-injury-investigating-the-role-of-innate-immune-responses
#19
Lisl Km Shoda, Christina Battista, Scott Q Siler, David S Pisetsky, Paul B Watkins, Brett A Howell
Drug-induced liver injury (DILI) remains an adverse event of significant concern for drug development and marketed drugs, and the field would benefit from better tools to identify liver liabilities early in development and/or to mitigate potential DILI risk in otherwise promising drugs. DILIsym software takes a quantitative systems toxicology approach to represent DILI in pre-clinical species and in humans for the mechanistic investigation of liver toxicity. In addition to multiple intrinsic mechanisms of hepatocyte toxicity (ie, oxidative stress, bile acid accumulation, mitochondrial dysfunction), DILIsym includes the interaction between hepatocytes and cells of the innate immune response in the amplification of liver injury and in liver regeneration...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28611662/an-antifungal-mechanism-of-protolichesterinic-acid-from-the-lichen-usnea-albopunctata-lies-in-the-accumulation-of-intracellular-ros-and-mitochondria-mediated-cell-death-due-to-apoptosis-in-candida-tropicalis
#20
S N Kumar, C Mohandas
Candida species causes superficial and life-threatening systemic infections and are difficult to treat due to the resistance of these organism to various clinically used drugs. Protolichesterinic acid is a well-known lichen compound. Although the antibacterial activity of protolichesterinic acid has been reported earlier, the antifungal property and its mechanism of action are still largely unidentified. The goal of the present investigation is to explore the anticandidal activity and mechanism of action of protolichesterinic acid, especially against Candida tropicalis...
2017: Frontiers in Pharmacology
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