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Mitochondrial toxicity

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https://www.readbyqxmd.com/read/28324764/enhancing-mitofusin-marf-ameliorates-neuromuscular-dysfunction-in-drosophila-models-of-tdp-43-proteinopathies
#1
Bilal Khalil, Marie-Jeanne Cabirol-Pol, Laetitia Miguel, Alexander J Whitworth, Magalie Lecourtois, Jean-Charles Liévens
Transactive response DNA-binding protein 43 kDa (TDP-43) is considered a major pathological protein in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The precise mechanisms by which TDP-43 dysregulation leads to toxicity in neurons are not fully understood. Using TDP-43-expressing Drosophila, we examined whether mitochondrial dysfunction is a central determinant in TDP-43 pathogenesis. Expression of human wild-type TDP-43 in Drosophila neurons results in abnormally small mitochondria...
February 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28323756/tdf-associated-renal-tubular-dysfunction-non-invasive-assessment-of-mitochondrial-injury
#2
Ryan Samuels, Carla Roca Bayerri, John A Sayer, D Ashley Price, Brendan Ai Payne
OBJECTIVE: To determine whether TDF-associated renal tubular dysfunction is associated with evidence of mitochondrial injury in urine. DESIGN: Single centre cross-sectional observational study of HIV positive outpatients. METHODS: Biochemistry was performed on paired serum and urine samples. Mitochondrial DNA (mtDNA) was studied by real-time PCR and long-range PCR on cellular fractions of urine. RESULTS: 48 subjects were enrolled of whom half were TDF-treated...
March 18, 2017: AIDS
https://www.readbyqxmd.com/read/28320040/mitochondria-as-a-target-for-the-cardioprotective-effects-of-cydonia-oblonga-mill-and-ficus-carica-l-in-doxorubicin-induced-cardiotoxicity
#3
Saman Gholami, Mir-Jamal Hosseini, Leila Jafari, Fatemeh Omidvar, Mohammad Kamalinejad, Vida Mashayekhi, Seyed Hojjat Hosseini, Azin Kardan, Jalal Pourahmad, Mohammad Reza Eskandari
Quince (Cydonia oblonga Mill.) and fig (Ficus carica L.) exhibit a broad spectrum of pharmacological activities. Regarding the cardiotoxic effect of doxorubicin (DOX) is mediated mainly through mitochondrial oxidative stress and dysfunction; the present study evaluated the cardioprotective effects of the aqueous extracts of Cydonia oblonga Mill. fruit (ACO) and Ficus carica L. fruit (AFC) against DOX-induced cardiotoxicity. Cardiomyocytes toxicity was induced in male Sprague Dawley rats by intraperitoneal (ip) injections of 2...
March 20, 2017: Drug Research
https://www.readbyqxmd.com/read/28319143/toxicity-effects-of-di-2-ethylhexyl-phthalate-to-eisenia-fetida-at-enzyme-cellular-and-genetic-levels
#4
Tingting Ma, Wei Zhou, Li'ke Chen, Longhua Wu, Peter Christie, Haibo Zhang, Yongming Luo
Di-(2-ethylhexyl) phthalate (DEHP) is a dominant phthalic acid ester (PAE) that has aroused public concern due to its resistance to degradation and its toxicity as an endocrine-disrupting compound. Effects of different concentrations of DEHP on Eisenia fetida in spiked natural soil have been studied in the body of the earthworm by means of soil cultivation tests 7, 14, 21 and 28 days after exposure. The results indicated that, in general, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, metallothionein (MT) content, the expression of heat shock protein 70 (HSP 70) and all the tested geno-toxicity parameters are promoted as time elapses and with increasing concentration of DEHP...
2017: PloS One
https://www.readbyqxmd.com/read/28318508/effects-of-novel-brominated-flame-retardant-tbph-and-its-metabolite-tbmehp-on-human-vascular-endothelial-cells-implication-for-human-health-risks
#5
Ping Xiang, Rong-Yan Liu, Hong-Jie Sun, Yun-Wen Yang, Xin-Yi Cui, Lena Q Ma
As a replacement for polybrominated diphenyl ethers, bis-(2-ethylhexyl) tetrabromophthalate (TBPH) is widely used as a novel flame retardant and has been detected in many environmental matrix including human blood. TBPH can be metabolized into mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) by carboxylesterase. However, their adverse effects on human vascular endothelium and their potential impacts on human cardiovascular disease are unknown. In this study, their adverse effects and associated molecular mechanisms on human vascular endothelial cells (HUVECs) were investigated...
March 16, 2017: Environmental Research
https://www.readbyqxmd.com/read/28302478/molecular-mechanisms-of-discrotophos-induced-toxicity-in-hepg2-cells-the-role-of-csa-in-oxidative-stress
#6
You-Cheng Hseu, Tung-Wei Hsu, Heng-Dao Lin, Chin Hui Chen, Ssu Ching Chen
Dicrotophos (Dic), an insecticide and acaricide, is used against a variety of sucking, boring and chewing pests. It was proven that Dic induced oxidative DNA damage in HepG2 cells. However, the molecular mechanisms of this compound were still unclear. First of all, the cytotoxicity and oxidative DNA damage were confirmed. Next, using RNA-seq for detecting differential expressed genes (DEGs) in cells treated with 50 μM Dic for 24 h, we showed that the dysregulation of these genes, irrespective of up (1298 genes) or down (2125 genes) regulation, could be attributed to some diverse pathways/metabolisms using KEGG analysis, particularly in DNA damage responses (DDRs) such as oxidative phosphorylation, nucleotide excision repair and cell cycle arrest...
March 13, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28301251/chrysin-as-an-anti-cancer-agent-exerts-selective-toxicity-by-directly-inhibiting-mitochondrial-complex-ii-and-v-in-cll-b-lymphocytes
#7
Ahmad Salimi, Mehryar Habibi Roudkenar, Enayatollah Seydi, Leila Sadeghi, Alireza Mohseni, Nahal Pirahmadi, Jalal Pourahmad
We investigated the effect of chrysin on isolated normal and chronic lymphocytic leukemia (CLL) B-lymphocytes and their isolated mitochondria. We report that a selective and significant increase in cytotoxicity, intracellular reactive oxygen species, mitochondrial membrane potential collapse, ADP/ATP ratio, caspase 3 activation and finally apoptosis in chrysin-treated CLL B- lymphocytes. Also we determined that chrysin selectively inhibits complex II and ATPases in cancerous mitochondria. In this study we proved that the ability of chrysin to promote apoptosis in CLL B-lymphocytes performed by selectively targeting of mitochondria...
March 16, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28296041/mitochondrial-oxidative-stress-and-dysfunction-induced-by-single-and-multi-wall-carbon-nanotubes-a-comparative-study
#8
Parvaneh Naserzadeh, Fatemeh Ghanbary, Enayatollah Seydi, Alireza Ghasemi, Mohammad Taghi Joghataei, Khadijeh Ashtari, Mohsen Akbari
With the ever-increasing use of carbon nanotubes (CNTs) in health-related and engineering applications, the hazardous risks of this material have become a major concern. It is well-known that CNTs accumulate with cytotoxic and genotoxic levels within vital organs. It has also been shown that treating cell cultures with CNTs resulted in cell cycle arrest and increased apoptosis/necrosis. The goal of this pilot study is to perform a comprehensive comparative study on the toxicity of single-wall (SW) and multi-wall (MW) carbon nanotubes in rat skin cells...
March 10, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28292679/evaluation-of-cytotoxicity-genotoxicity-and-apoptosis-of-wastewater-before-and-after-disinfection-with-performic-acid
#9
Patrizia Ragazzo, Donatella Feretti, Silvano Monarca, Luca Dominici, Elisabetta Ceretti, Gaia Viola, Valentina Piccolo, Nicoletta Chiucchini, Milena Villarini
Disinfection with performic acid (PFA) represents an emerging technology in wastewater treatment. Many recent studies indicate its effectiveness and suitability as a disinfectant for different applications; several have demonstrated its reliability as an alternative to chlorine for disinfecting secondary effluents from urban wastewater treatment plants (WWTPs). Some disinfection technologies, in relation to their oxidative power, lead to the formation of disinfection by-products (DBPs), some of which are of concern for their toxic and carcinogenic potential...
March 7, 2017: Water Research
https://www.readbyqxmd.com/read/28292652/synthesis-and-toxicity-assessment-of-3-oxobutanamides-against-human-lymphocytes-and-isolated-mitochondria
#10
Nima Razzaghi-Asl, Enaytollah Seydi, Radin Alikhani, Saba Rezvani, Ramin Miri, Ahmad Salimi
To reduce costly late-phase compound scrubbing, there has been an increased focus on assessing compounds within in vitro assays that predict properties of human safety liabilities, before preclinical in vivo studies. The aim of our study was to answer the questions that whether the toxicity risk of a series of 3-oxobutanamide derivatives could be predicted by using of human lymphocytes and their isolated mitochondria. Using biochemical and flow cytometry assessments, we demonstrated that exposure of lymphocytes and isolated mitochondria to five 3-oxobutanamide derivatives (1-5) did not exhibit remarkable toxicity at low concentrations (50-500μM) but toxicity could be observed at high concentrations (1000 and 2000μM), particularly for N-(5-(4-bromophenyl)-3-isoxazolyl)-3-oxobutanamide (4) and N-(2-benzothiazolyl)-3-oxo butanamide (5)...
March 7, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28292619/obesity-and-female-infertility-potential-mediators-of-obesity-s-impact
#11
REVIEW
Darcy E Broughton, Kelle H Moley
The worldwide upward trend in obesity has been dramatic, now affecting more than 20% of American women of reproductive age. Obesity is associated with many adverse maternal and fetal effects prenatally, but it also exerts a negative influence on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. Women with polycystic ovarian syndrome who are also obese demonstrate a more severe metabolic and reproductive phenotype. Obese women have reduced fecundity even when eumenorrheic and demonstrate poorer outcomes with the use of in vitro fertilization...
March 11, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28289825/the-highly-bioactive-molecule-and-signal-substance-6-formylindolo-3-2-b-carbazole-ficz-plays-bi-functional-roles-in-cell-growth-and-apoptosis-in-vitro
#12
Afshin Mohammadi-Bardbori, Farzaneh Bastan, Amin-Reza Akbarizadeh
The maintenance of cellular homeostasis is a complex process that is governed by the receipt of prototypical growth and death signals. The endogenous functions of aryl hydrocarbon receptor (AHR) in cellular homeostasis are not well understood. We aimed to establish whether the disturbance of endogenously activated AHR can influence cell growth, and if so, what mechanism(s) are involved. Cell growth was measured in mouse hepatoma Hepa-1 wild-type and cytochrome P4501A1 (CYP1A1)-deficient c37 cells. In other sets of experiments, HepG2 cells were exposed to different doses of FICZ (0...
March 13, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28289821/single-dose-local-anesthetics-exhibit-a-type-dose-and-time-dependent-chondrotoxic-effect-on-chondrocytes-and-cartilage-a-systematic-review-of-the-current-literature
#13
REVIEW
Peter Cornelius Kreuz, Matthias Steinwachs, Peter Angele
PURPOSE: Many studies have shown that local anesthetics may impede chondrocyte metabolism. However, the influence of a single-dose local anesthetics is controversial. The aim of this metaanalysis was to review the literature for studies investigating the cytotoxic effects of single-dose local anesthetics on chondrocytes and cartilage. METHODS: A comprehensive literature search was performed using established search engines (Medline, Embase) to identify studies, investigating the influence of single-dose local anesthetics on cartilage...
March 13, 2017: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
https://www.readbyqxmd.com/read/28288859/mitochondrial-toxicity-of-perfluorooctane-sulfonate-in-mouse-embryonic-stem-cell-derived-cardiomyocytes
#14
Lei-Lei Tang, Jia-Dan Wang, Ting-Ting Xu, Zhe Zhao, Jia-Jie Zheng, Ren-Shan Ge, Dan-Yan Zhu
Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may cause cardiotoxicity in animals and humans. However, little is known about the underlying mechanism by which it affects the organelle toxicity in cardiomyocytes during the cardiogenesis. Our previous proteomic study showed that differences of protein expression mainly existed in mitochondria of cardiomyocytes differentiated from embryonic stem (ES) cells after exposure to PFOS. Here, we focused on mitochondrial toxicity of PFOS in ES cell-derived cardiomyocytes...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28288821/reversal-of-cisplatin-resistance-in-human-gastric-cancer-cells-by-a-wogonin-conjugated-pt-iv-prodrug-via-attenuating-casein-kinase-2-mediated-nuclear-factor-%C3%AE%C2%BAb-pathways
#15
Feihong Chen, Xiaodong Qin, Gang Xu, Shaohua Gou, Xiufeng Jin
Pt(IV) prodrugs, with two additional coordination sites in contrast to Pt(II) drugs, have been actively studied nowadays, for they can perform well in enhancing the accumulation and retention of the corresponding Pt(II) drugs in cancer cells. Our designed Pt(II) drug, DN604, was recently found to exhibit significant anticancer activity and low toxicity. While, wogonin, a naturally O-methylated flavones, has been widely investigated for its tumor therapeutic potential. Thus, two Pt(IV)-based prodrugs were derived by addition of a wogonin unit to the axial position of DN604 and its analogue DN603 via a linker group...
March 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28286566/gastrointestinal-manifestations-of-mitochondrial-disorders-a-systematic-review
#16
REVIEW
Josef Finsterer, Marlies Frank
Mitochondrial disorders (MIDs) due to respiratory-chain defects or nonrespiratory chain defects are usually multisystem conditions [mitochondrial multiorgan disorder syndrome (MIMODS)] affecting the central nervous system (CNS), peripheral nervous system, eyes, ears, endocrine organs, heart, kidneys, bone marrow, lungs, arteries, and also the intestinal tract. Frequent gastrointestinal (GI) manifestations of MIDs include poor appetite, gastroesophageal sphincter dysfunction, constipation, dysphagia, vomiting, gastroparesis, GI pseudo-obstruction, diarrhea, or pancreatitis and hepatopathy...
January 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28286432/decreased-uptake-and-enhanced-mitochondrial-protection-underlie-reduced-toxicity-of-nanoceria-in-human-monocyte-derived-macrophages
#17
Salik Hussain, Preeti P Kodavanti, Jamie D Marshburn, Agnes Janoshazi, Stella M Marinakos, Margaret George, Annette Rice, Mark R Wiesner, Stavros Garantziotis
Cerium dioxide nanoparticles (nanoceria), currently used as catalysts including additives to diesel fuel, also present potential as a novel therapeutic agent for disorders involving oxidative stress. However, little is known about the effects of nanoceria on primary human cells involved in the innate immune response. Here, we evaluate nanoceria effects on monocyte derived macrophages (MDMs) from healthy human subjects. Peripheral blood monocytes were isolated from healthy human volunteers. MDMs were obtained by maturing monocytes over a five-day period...
December 2016: Journal of Biomedical Nanotechnology
https://www.readbyqxmd.com/read/28286310/joint-toxicity-of-chlorpyrifos-and-cadmium-on-the-oxidative-stress-and-mitochondrial-damage-in-neuronal-cells
#18
Ming-Yuan Xu, Pan Wang, Ying-Jian Sun, Lin Yang, Yi-Jun Wu
Pesticides and heavy metals can be easily biomagnified in food chains and bioaccumulated in individuals, thus pose significant threat to human health. However, their joint toxicity for long-term exposure at low dose has not been thoroughly investigated. In the present study, we investigated the oxidative damages in brain of rats exposed subchronically to organophosphorus pesticide chlorpyrifos (CPF) and heavy metal cadmium (Cd), and their mixtures at the environmentally relevant doses. Rats were given different doses of CPF and Cd by oral gavage for three months...
March 9, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28285348/n-adamantyl-4-methylthiazol-2-amine-attenuates-glutamate-induced-oxidative-stress-and-inflammation-in-the-brain
#19
Seung-Ju Yang, Eun-A Kim, Min-Jun Chang, Jiae Kim, Jung-Min Na, Soo Young Choi, Sung-Woo Cho
In this study, we explored the possible mechanisms underlying the neuroprotective and anti-oxidative effects of N-adamantyl-4-methylthiazol-2-amine (KHG26693) against in vivo glutamate-induced toxicity in the rat cerebral cortex. Our results showed that pretreatment with KHG26693 significantly attenuated glutamate-induced elevation of lipid peroxidation, tumor necrosis factor-α, interferon gamma, IFN-γ, interleukin-1β, nitric oxide, reactive oxygen species, NADPH oxidase, caspase-3, calpain activity, and Bax...
March 11, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28284974/mevalonolactone-disrupts-mitochondrial-functions-and-induces-permeability-transition-pore-opening-in-rat-brain-mitochondria-implications-for-the-pathogenesis-of-mevalonic-aciduria
#20
Cristiane Cecatto, Alexandre Umpierrez Amaral, Janaína Camacho da Silva, Alessandro Wajner, Kálita Dos Santos Godoy, Rafael Teixeira Ribeiro, Aline de Mello Gonçalves, Carmen Regla Vargas, Moacir Wajner
Mevalonic aciduria (MVA) is caused by severe deficiency of mevalonic kinase activity leading to tissue accumulation and high urinary excretion of mevalonic acid (MA) and mevalonolactone (ML). Patients usually present severe neurologic symptoms whose pathophysiology is poorly known. Here, we tested the hypothesis that the major accumulating metabolites are toxic by investigating the in vitro effects of MA and ML on important mitochondrial functions in rat brain and liver mitochondria. ML, but not MA, markedly decreased mitochondrial membrane potential (ΔΨm), NAD(P)H content and the capacity to retain Ca(2+) in the brain, besides inducing mitochondrial swelling...
March 8, 2017: Neurochemistry International
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