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Benxu Cheng, Pinki Anand, Anxiu Kuang, Feroz Akhtar, Virginia L Scofield
Ubiquitin proteasome system (UPS) dysfunction has been implicated in the development of many neuronal disorders, including Parkinson's disease (PD). Previous studies focused on individual neuroprotective agents and their respective abilities to prevent neurotoxicity following a variety of toxic insults. However, the effects of the antioxidant N-acetylcysteine (NAC) on proteasome impairment-induced apoptosis have not been well characterized in human neuronal cells. The aim of this study was to determine whether cotreatment of NAC and insulin-like growth factor-1 (IGF-1) efficiently protected against proteasome inhibitor-induced cytotoxicity in SH-SY5Y cells...
2016: Parkinson's Disease
Margaret L Salisbury, David A Lynch, Edwin J R van Beek, Ella A Kazerooni, Junfeng Guo, Meng Xia, Susan Murray, Kevin J Anstrom, Eric Yow, Fernando J Martinez, Eric A Hoffman, Kevin R Flaherty
RATIONALE: Adaptive Multiple Features Method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns. OBJECTIVES: We evaluated AMFM and visual quantification of HRCT patterns and their relationship with disease progression in Idiopathic Pulmonary Fibrosis. METHODS: IPF patients in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish. Proportion of lung occupied by ground glass, ground glass-reticular (GGR), honeycombing, emphysema, and normal were measured by AMFM and 3 radiologists, documenting baseline disease extent and post-baseline change...
October 21, 2016: American Journal of Respiratory and Critical Care Medicine
Alessandro Minarini, Silvia Ferrari, Martina Galletti, Nina Giambalvo, Daniela Perrone, Giulia Rioli, Gian Maria Galeazzi
N-acetylcysteine (NAC) is widely known for its role as a mucolytic and as an antidote to paracetamol overdose. There is increasing interest in the use of NAC in the treatment of several psychiatric disorders. The rationale for the administration of NAC in psychiatric conditions is based on its role as a precursor to the antioxidant glutathione, and its action as a modulating agent of glutamatergic, dopaminergic, neurotropic and inflammatory pathways. Areas covered: This study reviews the available data regarding the use of NAC in different psychiatric disorders including substance use disorders, autism, obsessive-compulsive spectrum disorders, schizophrenia, depression, bipolar disorder...
October 21, 2016: Expert Opinion on Drug Metabolism & Toxicology
Abhishek Srivastava, Vijender Panduga, Ramanatha Saralaya, Prabhakar Kr, Shahul Hameed, Suresh Solapure, Vinayak Hosagrahara
During the course of metabolic profiling of lead Compound 1, glutathione (GSH) conjugates were detected in rat bile, suggesting the formation of reactive intermediate precursor(s). This was confirmed by the identification of GSH and N-acetylcysteine (NAC) conjugates in microsomal incubations. It was proposed that bioactivation of Compound 1 occurs via the formation of a di-iminoquinone reactive intermediate through the involvement of the C-2 and C-5 nitrogens of the pyrimidine core. To further investigate this hypothesis, structural analogues with modifications at the C-5 nitrogen were studied for metabolic activation in human liver microsomes supplemented with GSH/NAC...
October 18, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Christina Jiun-Yu Tan, Grant E Sklar
INTRODUCTION: Paracetamol is the most common pharmaceutical agent implicated in toxic exposure in Singapore. This study aimed to describe the characteristics of paracetamol overdose in the adult population managed at a tertiary healthcare facility in Singapore. METHODS: Medical records of adult patients hospitalised with a diagnosis of paracetamol overdose at National University Hospital, Singapore, over a three-year period from January 2011 to December 2013 were retrospectively reviewed...
October 18, 2016: Singapore Medical Journal
Liying Guo, Kai Tan, Hao Wang, Xuan Zhang
Hepatocellular carcinoma (HCC) is one of the most common malignancies and the second cause of cancer-related deaths around the world. Pterostilbene (PTE), is a natural analog of resveratrol, possessing diverse pharmacological activities. In the present study, we aimed to examine the effect of PTE on tumor growth in mouse models of HCC and to elucidate the possible molecular mechanism in vivo and in vitro. We showed that PTE dose-dependently suppressed tumor growth in mice induced by diethylnitrosamine plus carbon tetrachloride, as evidenced by a decrease in the number of tumors and in the maximum size of the tumors...
October 5, 2016: Oncology Reports
Guangyong Chen, Yangdong Han, Wang He, Feng Liang
In the present study, we evaluated the protective effects of amentoflavone (AMF) against high-fat (HF) diet-induced metabolic dysfunction and focused on the influence of AMF on adipogenic differentiation during 3T3-L1 adipocyte differentiation. For this purpose, male Wistar rats were fed a HF diet or a HF diet with AMF (10 or 50 mg/kg). We found that AMF protected against HF diet-induced metabolic dysfunction in a dose-dependent manner, as evidenced by a decrease in the fasting blood glucose levels, fasting insulin levels and the homeostatic model assessment-insulin resistance index (HOMA‑IR), as well as by a decrease in the glucose level, as shown by the intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test...
October 14, 2016: International Journal of Molecular Medicine
Cassiana Mazon Fraga, Cristiane Damiani Tomasi, Danusa de Castro Damasio, Francieli Vuolo, Cristiane Ritter, Felipe Dal-Pizzol
BACKGROUND: The aim was to test the primary hypothesis that in patients suffering from shock, treatment with N-acetylcysteine (NAC) plus deferoxamine (DFX) decreases the incidence of acute kidney injury (AKI). METHODS: A double-blind, randomized, placebo-controlled trial was conducted in a general intensive care unit in an academic hospital. Patients were included if they had new-onset hypotension, defined as mean arterial blood pressure <60 mmHg or requirement for vasopressor medication...
October 17, 2016: Critical Care: the Official Journal of the Critical Care Forum
S H Lauz Medeiros, A de Oliveira Menezes, L Zogbi, E Frasson de Souza Montero
BACKGROUND: The ischemia/reperfusion (I/R) phenomenon can cause the dysfunction of some transplanted organs and other distant organs. Liver surgery success, including transplantations, may depend on the adverse effects of intestinal mucosa injury arising from temporary porta triad occlusion. The study objective was to examine I/R liver effects on the small intestine in rats after N-acetylcysteine (NAC) treatment. METHODS: Twenty-four male Wistar rats were randomly divided into 2 groups...
September 2016: Transplantation Proceedings
Giulia Landini, Tiziana Di Maggio, Francesco Sergio, Jean-Denis Docquier, Gian Maria Rossolini, Lucia Pallecchi
The effect of high NAC concentrations (10 and 50 mM) on antibiotic activity against 40 strains of respiratory pathogens was investigated. NAC compromised carbapenem activity (mostly imipenem and, to a lesser extent, meropenem and ertapenem) in a dose-dependent fashion. Chemical instability of carbapenems in the presence of NAC was demonstrated. With other antibiotics, 10 mM NAC had no major effects, while 50 mM NAC sporadically decreased (ceftriaxone and aminoglycosides) or increased (penicillins) antibiotic activity...
October 10, 2016: Antimicrobial Agents and Chemotherapy
Sudie E Back, Jenna L McCauley, Kristina J Korte, Daniel F Gros, Virginia Leavitt, Kevin M Gray, Mark B Hamner, Stacia M DeSantis, Robert Malcolm, Kathleen T Brady, Peter W Kalivas
OBJECTIVE: The antioxidant N-acetylcysteine is being increasingly investigated as a therapeutic agent in the treatment of substance use disorders (SUDs). This study explored the efficacy of N-acetylcysteine in the treatment of posttraumatic stress disorder (PTSD), which frequently co-occurs with SUD and shares impaired prefrontal cortex regulation of basal ganglia circuitry, in particular at glutamate synapses in the nucleus accumbens. METHODS: Veterans with PTSD and SUD per DSM-IV criteria (N = 35) were randomly assigned to receive a double-blind, 8-week course of N-acetylcysteine (2,400 mg/d) or placebo plus cognitive-behavioral therapy for SUD (between March 2013 and April 2014)...
October 11, 2016: Journal of Clinical Psychiatry
Wating Su, Yuan Zhang, Qiongxia Zhang, Jinjin Xu, Liying Zhan, Qiqi Zhu, Qingquan Lian, Huimin Liu, Zhong-Yuan Xia, Zhengyuan Xia, Shaoqing Lei
BACKGROUND: Patients with diabetes are prone to develop cardiac hypertrophy and more susceptible to myocardial ischemia-reperfusion (I/R) injury, which are concomitant with hyperglycemia-induced oxidative stress and impaired endothelial nitric oxide (NO) synthase (eNOS)/NO signaling. Caveolae are critical in the transduction of eNOS/NO signaling in cardiovascular system. Caveolin (Cav)-3, the cardiomyocytes-specific caveolae structural protein, is decreased in the diabetic heart in which production of reactive oxygen species are increased...
October 12, 2016: Cardiovascular Diabetology
Fenglian Shan, Zewei Shao, Shenghua Jiang, Zhaozhong Cheng
Although erlotinib (ERL) has drawn more and more attention toward its anticancer properties effect, the underlying mechanisms of ERL's anticancer properties effect remain unclear yet. So, the aim of this research was to explore the underlying anticancer mechanisms of ERL and to explore whether the reactive oxygen species (ROS)-dependent c-Jun N-terminal kinase (JNK) pathway contributed to the anticancer properties provided by ERL. In our study, we used MTT assay to detect the anticell growth ability of ERL on human non-small-cell lung cancer cell lines (A549)...
October 10, 2016: Cancer Medicine
Patrícia Santos, Ana P Herrmann, Radharani Benvenutti, Guilherme Noetzold, Franciele Giongo, Clarissa S Gama, Angelo L Piato, Elaine Elisabetsky
Anxiety disorders are highly prevalent and often result in poor quality of life. Available anxiolytics show significant adverse effects as well as partial efficacy in a sizable part of patients. Innovative treatments with more favorable risk-benefit ratio are sorely needed. A growing body of clinical data indicates the benefits of N-acetylcysteine (NAC) in psychiatric conditions. NAC modulates antioxidant, glutamatergic, inflammatory and neurotrophic pathways in the central nervous system, all of which are relevant to anxiety pathology...
October 7, 2016: Behavioural Brain Research
Hao Zhang, Weipeng Su, Zhixiong Ying, Yueping Chen, Le Zhou, Yue Li, Jingfei Zhang, Lili Zhang, Tian Wang
PURPOSE: The objective of the present study was to test the hypothesis that N-acetylcysteine (NAC) may play beneficial roles against intrauterine growth retardation (IUGR)-induced hepatic damage in suckling piglets. METHODS: Fourteen IUGR and seven normal birth weight (NBW) neonatal male piglets were selected. Piglets were weaned at 7 days of postnatal age and fed the control formula milk (NBW-CON and IUGR-CON groups) or the control formula milk supplemented with 1...
October 8, 2016: European Journal of Nutrition
Mohamed Abd-Elbaset, El-Shaimaa A Arafa, Gamal A El Sherbiny, Mohamed S Abdel-Bakky, Abdel Nasser A M Elgendy
Oxidative and nitrosative stress-induced endothelial cell damage play an essential role in the pathogenesis of hepatic ischemia-reperfusion (IR) injury. IR is associated with reduced eNOS expression and exacerbated by superimposed stress. NOSTRIN induces intracellular endothelial nitric oxide synthase (eNOS) translocation and inducible nitric oxide synthase (iNOS) increases nitric oxide (NO) production. Our aim was to assess hepatic expression of iNOS, eNOS, and NOSTRIN in IR with or without N-acetylcysteine (NAC) or thymoquinone (TQ) pretreatment and to compare their hepatoprotective effects...
October 7, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Alexandra Mani, Chryssoula Staikou, Iosifina Karmaniolou, Nikolaos Orfanos, Anastassios Mylonas, Tzortzis Nomikos, Agathi Pafiti, Apostolos Papalois, Nikolaos Arkadopoulos, Vassilios Smyrniotis, Kassiani Theodoraki
AIM OF THE STUDY: To investigate the pulmonary oxidative stress and possible protective effect of N-Acetylcysteine (NAC) and Desferoxamine (DFX)in a porcine model subjected to hemorrhagic shock. MATERIALS AND METHODS: Twenty-one pigs were randomly allocated to Group-A (sham, n = 5), Group-B (fluid resuscitation, n = 8) and Group-C (fluid, NAC and DFX resuscitation, n = 8). Groups B and C were subjected to a 40-min shock period induced by liver trauma, followed by a 60-min resuscitation period...
August 15, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
Toshiro Hirai, Yasuo Yoshioka, Asako Udaka, Eiichiro Uemura, Tomoyuki Ohe, Hisae Aoshima, Jian-Qing Gao, Ken Kokubo, Takumi Oshima, Kazuya Nagano, Kazuma Higashisaka, Tadahiko Mashino, Yasuo Tsutsumi
The therapeutic effects of fullerene derivatives on many models of inflammatory disease have been demonstrated. The anti-inflammatory mechanisms of these nanoparticles remain to be elucidated, though their beneficial roles in allergy and autoimmune diseases suggest their suppressive potential in acquired immunity. Here, we evaluated the effects of C60 pyrrolidine tris-acid (C60-P) and polyhydroxylated fullerene (C60(OH)36) on the acquired immune response in vitro and in vivo. In vitro, both C60 derivatives had dose-dependent suppressive effects on T cell receptor-mediated activation of T cells and antibody production by B cells under anti-CD40/IL-4 stimulation, similar to the actions of the antioxidant N-acetylcysteine...
December 2016: Nanoscale Research Letters
Xiaole Su, Xinfang Xie, Lijun Liu, Jicheng Lv, Fujian Song, Vlado Perkovic, Hong Zhang
BACKGROUND: To simultaneously evaluate the relative efficacy of multiple pharmacologic strategies for preventing contrast-induced acute kidney injury (AKI). STUDY DESIGN: Systematic review containing a Bayesian network meta-analysis of randomized controlled trials. SETTING & POPULATION: Participants undergoing diagnostic and/or interventional procedures with contrast media. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials comparing the active drug treatments with each other or with hydration alone...
October 1, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Annelies Paridaens, Sarah Raevens, Isabelle Colle, Eliene Bogaerts, Yves-Paul Vandewynckel, Xavier Verhelst, Anne Hoorens, Leo A van Grunsven, Hans Van Vlierberghe, Anja Geerts, Lindsey Devisscher
BACKGROUND & AIMS: Acetaminophen overdose in mice is characterized by hepatocyte endoplasmic reticulum stress, which activates the unfolded protein response, and centrilobular hepatocyte death. We aimed at investigating the therapeutic potential of tauroursodeoxycholic acid, a hydrophilic bile acid known to have anti-apoptotic and endoplasmic reticulum stress reducing capacities, in experimental acute liver injury induced by acetaminophen overdose. METHODS: Mice were injected with 300 mg/kg acetaminophen, two hours prior to receiving tauroursodeoxycholic acid, N-acetylcysteine or a combination therapy, and were euthanized 24 hours later...
October 5, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
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