A Novel Sulfonamide, 4-FS, Reduces Ethanol Drinking and Physical Withdrawal Associated With Ethanol Dependence

Khan, Muhammad Sona; Trenet, Wulfran; Xing, Nancy; Sibley, Britta D.; Abbas, Muzaffar; al‐Rashida, Mariya; Rauf, Khalid; Mandyam, Chitra D.

doi:10.3390/ijms21124411

Cited by 3 publications

(1 citation statement)

References 104 publications

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“…Anesthetics are important chemical drugs that allow patients to undergo operations involving severe pain where the patient must not move, such as dental treatment ( 1 , 2 ). Propofol (2,6-diisopropylphenol) is one of the most commonly used intravenous anesthetics globally as the depth of anesthesia induced by propofol can be controlled to a greater degree compared with other anesthetics, such as midazolam, etomidate, thiopental sodium and ketamine ( 1 , 3 – 5 ).…”

Section: Introductionmentioning

confidence: 99%

Demethylation of HACE1 gene promoter by propofol promotes autophagy of human A549 cells

Yang

Zhao

et al. 2020

Oncol Lett

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Propofol (2,6-diisopropylphenol) is one of the most commonly used intravenous anesthetics and possesses a number of non-anesthetic effects, including antitumor function. The aim of the present study was to elucidate the antitumor molecular mechanism of propofol on A549 and H1299 cells. A549 and H1299 cells were treated in the presence or absence of different concentrations (0, 60 or 120 µmol) of propofol for different durations (0, 24, 48 or 72 h), and proliferation was detected by MTT and colony formation assays; the protein levels of optineurin (OPTN) ubiquitination, HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1), methyl-CpG binding domain protein 3 (MBD3) and Microtubule-associated protein 1A/1B-light chain 3 were detected by immunoblotting or quantitative (q)PCR; the methylation state of the HACE1 gene promoter was detected by bisulfite DNA sequencing; and binding of MBD3 on HACE1 gene promoter was detected by chromatin immunoprecipitation-qPCR. Propofol inhibited proliferation of A549 and H1299 cells and promoted HACE1-OPTN axis-mediated selective autophagy activity by increasing the protein expression levels of HACE1 via demethylating its promoter region. Furthermore, propofol promoted expression levels of MBD3 and binding to the-1,000 to-1 bp (transcription start site) region of HACE1 gene promoter. MBD3-knockdown experiments indicated that propofol inhibited proliferation of A549 cells in a MBD3-dependent manner. Thus, the findings of the present study provided a potential antitumor molecular mechanism mediated by propofol.

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Section: Introductionmentioning

confidence: 99%

Demethylation of HACE1 gene promoter by propofol promotes autophagy of human A549 cells

Yang

Zhao

et al. 2020

Oncol Lett

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Isoxazole‐9 reduces enhanced fear responses and retrieval in ethanol‐dependent male rats

Staples

Herman

Lockner

et al. 2021

J of Neuroscience Research

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Plasticity in the dentate gyrus (DG) is strongly influenced by ethanol, and ethanol experience alters long-term memory consolidation dependent on the DG. However, it is unclear if DG plasticity plays a role in dysregulation of long-term memory consolidation during abstinence from chronic ethanol experience. Outbred male Wistar rats experienced 7 weeks of chronic intermittent ethanol vapor exposure (CIE). Seventytwo hours after CIE cessation, CIE and age-matched ethanol-naïve Air controls experienced auditory trace fear conditioning (TFC). Rats were tested for cue-mediated retrieval in the fear context either twenty-four hours (24 hr), ten days (10 days), or twenty-one days (21 days) later. CIE rats showed enhanced freezing behavior during TFC acquisition compared to Air rats. Air rats showed significant fear retrieval, and this behavior did not differ at the three time points. In CIE rats, fear retrieval increased over time during abstinence, indicating an incubation in fear responses.Enhanced retrieval at 21 days was associated with reduced structural and functional plasticity of ventral granule cell neurons (GCNs) and reduced expression of synaptic proteins important for neuronal plasticity. Systemic treatment with the drug Isoxazole-9 (Isx-9; small molecule that stimulates DG plasticity) during the last week and a half of CIE blocked altered acquisition and retrieval of fear memories in CIE rats during abstinence. Concurrently, Isx-9 modulated the structural and functional plasticity of ventral GCNs and the expression of synaptic proteins in the ventral DG.These findings identify that abstinence-induced disruption of fear memory consolidation occurs via altered plasticity within the ventral DG, and that Isx-9 prevented these effects.

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Effect of 4-Fluoro-N-(4-Sulfamoylbenzyl) Benzene Sulfonamide on Acquisition and Expression of Nicotine-Induced Behavioral Sensitization and Striatal Adenosine Levels

Rehman¹,

Abbas²,

al‐Rashida³

et al. 2020

DDDT

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Introduction Behavioral sensitization is a phenomenon that develops from intermittent exposure to nicotine and other psychostimulants, which often leads to heightened locomotor activity and then relapse. Sulfonamides that act as carbonic anhydrase inhibitors have a documented role in enhancing dopaminergic tone and normalizing neuroplasticity by stabilizing glutamate release. Objective The aim of the current study was to explore synthetic sulfonamides derivative 4-fluoro-N-(4-sulfamoylbenzyl) benzene-sulfonamide (4-FBS) (with documented carbonic anhydrase inhibitory activity) on acquisition and expression of nicotine-induced behavioral sensitization. Methods In the acquisition phase, selected 5 groups of mice were exposed to saline or nicotine 0.5mg/kg intraperitoneal (i.p) for 7 consecutive days. Selected 3 groups were administered with 4-FBS 20, 40, and 60 mg/kg p.o. along with nicotine. After 3 days of the drug-free period, ie, day 11, a challenge dose of nicotine was injected to all groups except saline and locomotor activity was recorded for 30 minutes. In the expression phase, mice were exposed to saline and nicotine only 0.5 mg/kg i.p for 7 consecutive days. After 3 days of the drug-free period, ie, day 11, 4-FBS at 20, 40, and 60 mg/kg were administered to the selected groups, one hour after drug a nicotine challenge dose was administered, and locomotion was recorded. At the end of behavioral experiments, all animals were decapitated and the striatum was excised and screened for changes in adenosine levels, using HPLC-UV. Results Taken together, our findings showed that 4-FBS in all 3 doses, in both sets of experiments significantly attenuated nicotine-induced behavioral sensitization in mice. Additionally, 4-FBS at 60mg/kg significantly lowered the adenosine level in the striatum. Conclusion The behavioral and adenosine modulation is promising, and more receptors level studies are warranted to explore the exact mechanism of action of 4-FBS.

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A Novel Sulfonamide, 4-FS, Reduces Ethanol Drinking and Physical Withdrawal Associated With Ethanol Dependence

Cited by 3 publications

References 104 publications

Demethylation of <em>HACE1</em> gene promoter by propofol promotes autophagy of human A549 cells

Demethylation of <em>HACE1</em> gene promoter by propofol promotes autophagy of human A549 cells

Isoxazole‐9 reduces enhanced fear responses and retrieval in ethanol‐dependent male rats

<p>Effect of 4-Fluoro-N-(4-Sulfamoylbenzyl) Benzene Sulfonamide on Acquisition and Expression of Nicotine-Induced Behavioral Sensitization and Striatal Adenosine Levels</p>

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A Novel Sulfonamide, 4-FS, Reduces Ethanol Drinking and Physical Withdrawal Associated With Ethanol Dependence

Cited by 3 publications

References 104 publications

Demethylation of <em>HACE1</em> gene promoter by propofol promotes autophagy of human A549&nbsp;cells

Demethylation of <em>HACE1</em> gene promoter by propofol promotes autophagy of human A549&nbsp;cells

Isoxazole‐9 reduces enhanced fear responses and retrieval in ethanol‐dependent male rats

<p>Effect of 4-Fluoro-N-(4-Sulfamoylbenzyl) Benzene Sulfonamide on Acquisition and Expression of Nicotine-Induced Behavioral Sensitization and Striatal Adenosine Levels</p>

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Demethylation of <em>HACE1</em> gene promoter by propofol promotes autophagy of human A549 cells

Demethylation of <em>HACE1</em> gene promoter by propofol promotes autophagy of human A549 cells