Hepatic Cannabinoid Signaling in the Regulation of Alcohol-Associated Liver Disease

Lees, Briana; Debenham, Jennifer; Squeglia, Lindsay M.

doi:10.35946/arcr.v41.1.11

Cited by 20 publications

(1 citation statement)

References 290 publications

(257 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alcohol-associated liver disease (ALD) caused by chronic alcohol consumption has become one of the most important global health issues (K. Yang, Choi, & Jeong, 2021). Alcohol enters the body, and most of it will be metabolized in the liver.…”

Section: Introductionmentioning

confidence: 99%

Physcion alleviates chronic alcoholic hepatic inflammation and pyroptosis through SIRT1-AMPK activation

Bai

Guo

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

BACKGROUND AND PURPOSE Alcohol-associated liver disease (ALD) caused by chronic alcohol consumption range from simple steatosis to alcoholic hepatitis, fibrosis, and cirrhosis. Physcion is an anthraquinone compound of Rheum palmatum L, a Chinese herbal medicine with possible hepatoprotective properties. This study aimed to investigate the protective effect and associated molecular mechanisms of physcion on chronic alcoholic liver injury. EXPERIMENTAL APPROACH Chronic alcoholic liver injury was induced by placing male C57BL/6 mice on Lieber-DeCarli ethanol-containing diets for 10 days and then administering a single dose of ethanol (5 g/kg body weight) via gavage. Human hepatic stellate cells line, LX-2 cells were pretreated with physcion for 1 h prior to ethanol stimulation. KEY RESULTS Physcion effectively ameliorated ALD-induced serum aminotransferase and triglyceride levels, steatosis, activated SIRT1-AMPK signaling, then inhibited hepatic NLRP3 inflammasome activation and GSDMD relevant in pyroptosis, the same as the hepato-protection of AMPK and SIRT1 agonists. Physcion suppressed ECM accumulation through inhibiting collagen-Ⅰ and α-SMA expression. Moreover, physcion prevented the accumulation of HMGB1 and NF-κB p65 nuclear translocation and release. Importantly, silencing of SIRT1-AMPK signaling eliminates the protective effect of physcion. CONCLUSIONS AND IMPLICATIONS Activation of SIRT1-AMPK signaling is involved in ALD pathogenesis, which alleviated by physcion through inhibiting NLRP3 inflammasome activation, inflammatory response and pyroptosis. Therefore, manipulation of hepatic inflammation and pyroptosis through strategies by targeting SIRT1-AMPK signaling holds great therapeutic potential for ALD.

show abstract

Section: Introductionmentioning

confidence: 99%

Physcion alleviates chronic alcoholic hepatic inflammation and pyroptosis through SIRT1-AMPK activation

Bai

Guo

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

Effect of Selective Personality-Targeted Alcohol Use Prevention on 7-Year Alcohol-Related Outcomes Among High-risk Adolescents

et al. 2022

View full text Add to dashboard Cite

ImportanceAlcohol consumption is one of the leading preventable causes of burden of disease worldwide. Selective prevention of alcohol use can be effective in delaying the uptake and reducing harmful use of alcohol during the school years; however, little is known about the durability of these effects across the significant transition from early adolescence into late adolescence and early adulthood.ObjectiveTo examine the sustained effects of a selective personality-targeted alcohol use prevention program on alcohol outcomes among adolescents who report high levels of 1 of 4 personality traits associated with substance use.Design, Setting, and ParticipantsA cluster randomized clinical trial was conducted to assess the effectiveness of the selective personality-targeted PreVenture program on reducing the growth of risky alcohol use and related harms from early to late adolescence and early adulthood. Participants included grade 8 students attending 14 secondary schools across New South Wales and Victoria, Australia, in 2012 who screened as having high levels of anxiety sensitivity, negative thinking, impulsivity, and/or sensation seeking. Schools were block randomized to either the PreVenture group (7 schools) or the control group (7 schools). The primary end point of the original trial was 2 years post baseline; the present study extends the follow-up period from July 1, 2017, to December 1, 2019, 7 years post baseline. Data were analyzed from July 22, 2021, to August 2, 2022.InterventionsThe PreVenture program is a 2-session, personality-targeted intervention designed to upskill adolescents to better cope with their emotions and behaviors.Main Outcomes and MeasuresSelf-reported monthly binge drinking, alcohol-related harms, and hazardous alcohol use measured by the Alcohol Use Disorders Identification Test–Concise consumption screener.ResultsOf 438 participants (249 male [56.8%]; mean [SD] age, 13.4 [0.5] years) from 14 schools, 377 (86.2%) provided follow-up data on at least 2 occasions, and among those eligible, 216 (54.0%) participated in the long-term follow-up. Compared with the control condition, the PreVenture intervention was associated with reduced odds of any alcohol-related harm (odds ratio [OR], 0.81 [95% CI, 0.70-0.94]) and a greater mean reduction in the frequency of alcohol-related harms (β = −0.22 [95% CI, −0.44 to −0.003]) at the 7.0-year follow-up. There were no differences in the odds of monthly binge drinking (OR, 0.80 [95% CI, 0.56-1.13]) or hazardous alcohol use (OR, 0.87 [95% CI, 0.59-1.27]) at the 7.0-year follow-up. Exploratory analyses at the 5.5-year follow-up showed that compared with the control condition, the PreVenture intervention was also associated with reduced odds of monthly binge drinking (OR, 0.87, [95% CI, 0.77-0.99]) and hazardous alcohol use (OR, 0.91 [95% CI, 0.84-0.99]), but this was not sustained.Conclusions and RelevanceThis study demonstrated that a brief selective personality-targeted alcohol use prevention intervention delivered in the middle school years can have sustained effects into early adulthood.Trial Registrationanzctr.org.au Identifier: ACTRN12612000026820

show abstract

Drug‐impaired driving and traffic collisions: Study on a cross section of the Italian population

Odoardi

Biosa

Mestria

et al. 2022

Drug Testing and Analysis

View full text Add to dashboard Cite

The present study focuses on the association between road accidents and the presence of drugs of abuse markers in the biological fluids of the drivers. Biological fluids collected from 1236 drivers involved in road accidents (54 fatal and 1182 non-fatal crashes) in the Rome area were analyzed for alcohol and psychotropic drugs, as required by judicial authorities. The substance most frequently detected was alcohol (in 19% of non-fatal and 32% of fatal crashes), followed by cannabinoids (12% of non-fatal crashes) and cocaine (9% of non-fatal and 20% of fatal crashes). The results obtained for cocaine and cannabinoids in blood and urine were compared. We observed the absence or low concentrations of the active drug in blood (cocaine was often below 5 ng/ml and THC below 1 ng/ml), whereas urinary concentrations of metabolites were generally high (benzoylecgonine 250above 5000 ng/ml, THCCOOH 15-270 ng/ml). The risk of being involved in a road accident if cocaine or cannabis markers were present in the urine specimens was evaluated compared to a control population. The odds ratios calculated, being 8.13 for cannabis and 5.32 for cocaine, suggest a strong association between the presence of these drugs in the urine of drivers and traffic accidents, regardless of their presence in blood samples. The present data suggest that the chance of being involved in a road accident is higher than in the control population even if the subject is no longer "under the influence" of cannabis or cocaine at the time of the accident.

show abstract

Hepatic Cannabinoid Signaling in the Regulation of Alcohol-Associated Liver Disease

Cited by 20 publications

References 290 publications

Physcion alleviates chronic alcoholic hepatic inflammation and pyroptosis through SIRT1-AMPK activation

Physcion alleviates chronic alcoholic hepatic inflammation and pyroptosis through SIRT1-AMPK activation

Effect of Selective Personality-Targeted Alcohol Use Prevention on 7-Year Alcohol-Related Outcomes Among High-risk Adolescents

Drug‐impaired driving and traffic collisions: Study on a cross section of the Italian population

Contact Info

Product

Resources

About