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Respirology (Carlton, Vic.) Apr 2015
Topics: Acetylcysteine; Female; Humans; Idiopathic Pulmonary Fibrosis; Male; Pyridones
PubMed: 25678074
DOI: 10.1111/resp.12487 -
Assessing combined effects of varenicline and N-acetylcysteine on reducing nicotine seeking in rats.Addiction Biology Mar 2022Nicotine addiction is a chronic relapsing brain disorder, and cigarette smoking is the leading cause of preventable death in the United States. Currently, the most...
Nicotine addiction is a chronic relapsing brain disorder, and cigarette smoking is the leading cause of preventable death in the United States. Currently, the most effective pharmacotherapy for smoking cessation is Varenicline (VRN), which reduces both positive and negative reinforcement by nicotine. Clinically, VRN attenuates withdrawal symptoms and promotes abstinence, but >50% of smokers relapse within 3 months following a quit attempt. This may indicate that VRN fails to ameliorate components of nicotine-induced neuroplasticity that promote relapse vulnerability. Animal models reveal that glutamate dysregulation in the nucleus accumbens is associated with nicotine relapse. N-acetylcysteine (NAC) normalizes glutamate transmission and prolongs cocaine abstinence. Thus, combining VRN and NAC may promote and maintain, respectively, nicotine abstinence. In rats, we found that VRN effectively reduced nicotine self-administration and seeking in early abstinence, but not seeking later in abstinence. In contrast, NAC reduced seeking only later in abstinence. Because VRN and NAC are sometimes associated with mild adverse effects, we also evaluated a sequential approach combining subthreshold doses of VRN during self-administration and early abstinence with subthreshold doses of NAC during late abstinence. As expected, subthreshold VRN did not reduce nicotine intake. However, subthreshold VRN and NAC reduced seeking in late abstinence, suggesting a combined effect. Overall, our results suggest that combining subthreshold VRN and NAC is a viable and drug-specific approach to promote abstinence and reduce relapse while minimizing adverse effects. Our data also suggest that different components and time points in addiction engage the different neurocircuits targeted by VRN and NAC.
Topics: Acetylcysteine; Animals; Nicotine; Rats; Smoking Cessation; Tobacco Use Disorder; Varenicline
PubMed: 35229943
DOI: 10.1111/adb.13151 -
Dental Materials Journal May 2021This study examined the effects of N-acetylcysteine (NAC) on the inflammatory reactions of murine osteoblastic cells cultured on the 4-methacryloxyethyl trimellitate...
This study examined the effects of N-acetylcysteine (NAC) on the inflammatory reactions of murine osteoblastic cells cultured on the 4-methacryloxyethyl trimellitate anhydride/methyl methacrylate (4-META/MMA)-based resin. Superbond C&B (SB) was used as the 4-META/MMA-based resin and placed in a 48-well cell culture plate. The cells were cultured in αMEM (control) as well as on SB and SB in αMEM with NAC (SB+NAC). They were examined using the WST-1 proliferation assay, real-time PCR, enzyme-linked immunosorbent assay (ELISA), intracellular reactive oxygen species (ROS) measurements, and cellular glutathione (GSH) detection. COX-2 and IL-6 gene expressions were upregulated in SB; however, they were suppressed by NAC. Furthermore, PGE production in the culture medium was increased in SB, whereas NAC decreased the PGE production. NAC lowered the ROS level in the culture medium and significantly increased the intracellular GSH level. The present in vitro study demonstrated that NAC might be effective for dental material detoxification.
Topics: Acetylcysteine; Animals; Cells, Cultured; Dinoprostone; Methacrylates; Mice; Reactive Oxygen Species
PubMed: 33642448
DOI: 10.4012/dmj.2020-275 -
Pharmacological Reports : PR Oct 2021Substance use disorder (SUD) is a chronic brain condition, with compulsive and uncontrollable drug-seeking that leads to long-lasting and harmful consequences. The... (Review)
Review
Substance use disorder (SUD) is a chronic brain condition, with compulsive and uncontrollable drug-seeking that leads to long-lasting and harmful consequences. The factors contributing to the development of SUD, as well as its treatment settings, are not fully understood. Alterations in brain glutamate homeostasis in humans and animals implicate a key role of this neurotransmitter in SUD, while the modulation of glutamate transporters has been pointed as a new strategy to diminish the excitatory glutamatergic transmission observed after drugs of abuse. N-acetylcysteine (NAC), known as a safe mucolytic agent, is involved in the regulation of this system and may be taken into account as a novel pharmacotherapy for SUD. In this paper, we summarize the current knowledge on the ability of NAC to reduce drug-seeking behavior induced by psychostimulants, opioids, cannabinoids, nicotine, and alcohol in animals and humans. Preclinical studies showed a beneficial effect in animal models of SUD, while the clinical efficacy of NAC has not been fully established. In summary, NAC will be a small add-on to usual treatment and/or psychotherapy for SUD, however, further studies are required.
Topics: Acetylcysteine; Animals; Drug-Seeking Behavior; Expectorants; Extinction, Psychological; Humans; Substance-Related Disorders
PubMed: 34091880
DOI: 10.1007/s43440-021-00283-7 -
BMJ Clinical Evidence Sep 2008Acute renal failure is characterised by abrupt and sustained decline in glomerular filtration rate, which leads to accumulation of urea and other chemicals in the blood.... (Review)
Review
INTRODUCTION
Acute renal failure is characterised by abrupt and sustained decline in glomerular filtration rate, which leads to accumulation of urea and other chemicals in the blood. The term acute kidney injury has been recently introduced to encompass a wide spectrum of acute alterations in kidney function from very mild to severe. Acute renal failure/acute kidney injury is classified according to the RIFLE criteria where a change from baseline serum creatinine or urine output determines the level of renal dysfunction.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent acute renal failure in people at high risk? What are the effects of treatments for critically ill people with acute renal failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 77 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: albumin supplementation plus loop diuretics (intravenous), aminoglycosides, aminophylline, amphotericin B, calcium channel blockers, contrast media, dialysis membranes, dopamine, fenoldopam, loop diuretics, mannitol, N-acetylcysteine, natriuretic peptides, renal replacement therapy, sodium bicarbonate-based fluids, sodium chloride-based fluids, and theophylline.
Topics: Acetylcysteine; Acute Kidney Injury; Fenoldopam; Humans; Renal Dialysis; Renal Insufficiency; Renal Replacement Therapy
PubMed: 19445797
DOI: No ID Found -
Biomolecules Sep 2015This review on recent research advances of the lipid peroxidation product 4-hydroxy-nonenal (HNE) has four major topics: I. the formation of HNE in various organs and... (Review)
Review
This review on recent research advances of the lipid peroxidation product 4-hydroxy-nonenal (HNE) has four major topics: I. the formation of HNE in various organs and tissues, II. the diverse biochemical reactions with Michael adduct formation as the most prominent one, III. the endogenous targets of HNE, primarily peptides and proteins (here the mechanisms of covalent adduct formation are described and the (patho-) physiological consequences discussed), and IV. the metabolism of HNE leading to a great number of degradation products, some of which are excreted in urine and may serve as non-invasive biomarkers of oxidative stress.
Topics: Acetylcysteine; Animals; Fatty Acids, Unsaturated; Humans; Lipid Peroxidation; Oxidative Stress
PubMed: 26437435
DOI: 10.3390/biom5042247 -
Physiological Reviews Apr 2018This review focuses on one family of the known cAMP receptors, the exchange proteins directly activated by cAMP (EPACs), also known as the cAMP-regulated guanine... (Review)
Review
This review focuses on one family of the known cAMP receptors, the exchange proteins directly activated by cAMP (EPACs), also known as the cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs). Although EPAC proteins are fairly new additions to the growing list of cAMP effectors, and relatively "young" in the cAMP discovery timeline, the significance of an EPAC presence in different cell systems is extraordinary. The study of EPACs has considerably expanded the diversity and adaptive nature of cAMP signaling associated with numerous physiological and pathophysiological responses. This review comprehensively covers EPAC protein functions at the molecular, cellular, physiological, and pathophysiological levels; and in turn, the applications of employing EPAC-based biosensors as detection tools for dissecting cAMP signaling and the implications for targeting EPAC proteins for therapeutic development are also discussed.
Topics: Acetylcysteine; Animals; Cytoplasm; Erythromycin; Guanine Nucleotide Exchange Factors; Humans; Protein Transport; Receptors, Cyclic AMP; Signal Transduction
PubMed: 29537337
DOI: 10.1152/physrev.00025.2017 -
Nutrients May 2023Administering N-acetylcysteine (NAC) could counteract the effect of free radicals, improving the clinical evolution of patients admitted to the Intensive Care Unit... (Randomized Controlled Trial)
Randomized Controlled Trial
Administering N-acetylcysteine (NAC) could counteract the effect of free radicals, improving the clinical evolution of patients admitted to the Intensive Care Unit (ICU). This study aimed to investigate the clinical and biochemical effects of administering NAC to critically ill patients with COVID-19. A randomized controlled clinical trial was conducted on ICU patients ( 140) with COVID-19 and divided into two groups: patients treated with NAC (NAC-treated group) and patients without NAC treatment (control group). NAC was administered as a continuous infusion with a loading dose and a maintenance dose during the study period (from admission until the third day of ICU stay). NAC-treated patients showed higher PaO/FiO ( 0.014) after 3 days in ICU than their control group counterparts. Moreover, C-reactive protein ( 0.001), D-dimer ( 0.042), and lactate dehydrogenase ( 0.001) levels decreased on the third day in NAC-treated patients. Glutathione concentrations decreased in both NAC-treated ( 0.004) and control ( 0.047) groups after 3 days in ICU; whereas glutathione peroxidase did not change during the ICU stay. The administration of NAC manages to improve the clinical and analytical response of seriously ill patients with COVID-19 compared to the control group. NAC is able to stop the decrease in glutathione concentrations.
Topics: Humans; Acetylcysteine; COVID-19; Critical Illness; Glutathione; Dietary Supplements
PubMed: 37405379
DOI: 10.3390/nu15092235 -
Experimental Physiology Nov 2022What is the central question of this study? This study addresses whether a high-fat, high-sucrose diet causes cardiac and diaphragm muscle abnormalities in male rats and...
NEW FINDINGS
What is the central question of this study? This study addresses whether a high-fat, high-sucrose diet causes cardiac and diaphragm muscle abnormalities in male rats and whether supplementation with the antioxidant N-acetylcysteine reverses diet-induced dysfunction. What is the main finding and its importance? N-Acetylcysteine attenuated the effects of high-fat, high-sucrose diet on markers of cardiac hypertrophy and diastolic dysfunction, but neither high-fat, high-sucrose diet nor N-acetylcysteine affected the diaphragm. These results support the use of N-acetylcysteine to attenuate cardiovascular dysfunction induced by a 'Western' diet.
ABSTRACT
Individuals with overweight or obesity display respiratory and cardiovascular dysfunction, and oxidative stress is a causative factor in the general aetiology of obesity and of skeletal and cardiac muscle pathology. Thus, this preclinical study aimed to define diaphragmatic and cardiac morphological and functional alterations in response to an obesogenic diet in rats and the therapeutic potential of an antioxidant supplement, N-acetylcysteine (NAC). Young male Wistar rats consumed ad libitum a 'lean' or high-saturated fat, high-sucrose (HFHS) diet for ∼22 weeks and were randomized to control or NAC (2 mg/ml in the drinking water) for the last 8 weeks of the dietary intervention. We then evaluated diaphragmatic and cardiac morphology and function. Neither HFHS diet nor NAC supplementation affected diaphragm-specific force, peak power or morphology. Right ventricular weight normalized to estimated body surface area, left ventricular fractional shortening and posterior wall maximal shortening velocity were higher in HFHS compared with lean control animals and not restored by NAC. In HFHS rats, the elevated deceleration rate of early transmitral diastolic velocity was prevented by NAC. Our data showed that the HFHS diet did not compromise diaphragmatic muscle morphology or in vitro function, suggesting other possible contributors to breathing abnormalities in obesity (e.g., abnormalities of neuromuscular transmission). However, the HFHS diet resulted in cardiac functional and morphological changes suggestive of hypercontractility and diastolic dysfunction. Supplementation with NAC did not affect diaphragm morphology or function but attenuated some of the cardiac abnormalities in the rats receiving the HFHS diet.
Topics: Animals; Male; Rats; Acetylcysteine; Antioxidants; Diet, High-Fat; Fatty Acids; Obesity; Rats, Wistar; Respiratory Muscles; Sucrose
PubMed: 35938289
DOI: 10.1113/EP090332 -
British Journal of Clinical Pharmacology Jun 2016N-acetylcysteine (NAC) may be useful in the management of non-paracetamol drug-induced liver injury (DILI). Our objective was to review systematically evidence for the... (Review)
Review
AIMS
N-acetylcysteine (NAC) may be useful in the management of non-paracetamol drug-induced liver injury (DILI). Our objective was to review systematically evidence for the use of NAC as a therapeutic option for non-paracetamol DILI.
METHODS
We searched for randomized controlled trials (RCTs) and prospective cohort studies. We searched several bibliographic databases, grey literature sources, conference proceedings and ongoing trials. Our pre-specified primary outcomes were all cause and DILI related mortality, time to normalization of liver biochemistry and adverse events. Secondary outcomes were proportion receiving liver transplant, time to transplantation, transplant-free survival and hospitalization duration.
RESULTS
We identified one RCT of NAC vs. placebo in patients with non-paracetamol acute liver failure. There was no difference in the primary outcomes of overall survival at 3 weeks between NAC [70%, 95% confidence interval (CI) = 60%, 81%, n = 81] and placebo (66%, 95% CI = 56%, 77%, n = 92). NAC significantly improved the secondary outcomes of transplant-free survival compared with placebo: 40% NAC (95% CI = 28%, 51%) vs. 27% placebo (95% CI = 18%, 37%). A subgroup analysis according to aetiology found improved transplant-free survival in patients with non-paracetamol DILI, NAC (58%, n = 19) vs. placebo (27%, n = 26), odds ratio (OR) 0.27 (95% CI = 0.076, 0.942). Overall survival was similar, NAC (79%) vs. placebo (65%);, OR 0.50 (95% CI = 0.13, 1.98).
CONCLUSION
Current available evidence is limited and does not allow for any firm conclusions to be made regarding the role of NAC in non-paracetamol DILI. We therefore highlight the need for further research in this area.
Topics: Acetylcysteine; Chemical and Drug Induced Liver Injury; Free Radical Scavengers; Humans
PubMed: 26757427
DOI: 10.1111/bcp.12880