Advantages and disadvantages of disulfiram coadministered with popular addictive substances

Kleczkowska, Patrycja; Sulejczak, Dorota; Zaremba, M

doi:10.1016/j.ejphar.2021.174143

Cited by 12 publications

(9 citation statements)

References 81 publications

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“…Additionally, the harmful effects of alcohol particularly affect those of working age, with 139 million disability-adjusted life years lost, or 5.1% of the total global burden of disease, attributable to alcohol consumption ( 6 ). Although anti-alcoholic drugs including disulfiram ( 7 ), naltrexone and acamprosate ( 8 ) have been reported to have the anti-alcohol effect, there are few drugs currently available to treat humans. Therefore, the development of safe and effective natural products for alleviating AAI is of interest globally.…”

Section: Introductionmentioning

confidence: 99%

Six Types of Tea Reduce Acute Alcoholism in Mice by Enhancing Ethanol Metabolism, Suppressing Oxidative Stress and Inflammation

et al. 2022

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Acute alcoholic intoxication (AAI) is a pathological process of multiple system damage caused by a large amount of alcohol, especially in the liver. Although tea extracts alleviate AAI and alcohol-induced liver damage, the mechanisms underlying the protective actions of different types of Chinese tea are unclear. In this study, the AAI mice model was used to explore the functions and mechanisms of six types of tea extract (WEATs) in alleviating AAI. The losing righting reflexes of mice were evaluated to assess the effects of the WEATs on AAI. The levels of the ethanol metabolism enzymes (ADH, ALDH2, CYP2E1), the oxidative stress-related indicators (NRF-2, HO-1, SOD, GSH, CAT, and TG) and the inflammatory factors (TNF-α, iNOS, IL-6, and IL-10) were determined. Black tea and dark tea significantly shortened the sleep time (duration of the loss of righting reflex) and had a good sobering effect. Green tea and oolong tea had the dual effect of prolonging tolerance time (time of losing righting reflex) and shortening sleep time. While white tea had the most significant effect on prolonging tolerance time but with no obvious sobering effect. Black tea, dark tea, and oolong tea significantly up-regulated ADH and ALDH2, and down-regulated CYP2E1. Green tea and white tea significantly increased the levels of Nrf2, GSH, and CAT. Black tea, dark tea and oolong tea markedly increased the levels of HO-1, IL-10, and inhibited TG. Therefore, it is possible that black tea, dark tea and oolong tea reduced AAI by increasing ethanol metabolism, suppressing oxidative stress and inflammation. While green tea was mainly by regulating oxidative stress. White tea may prolong the tolerance time by increasing ethanol metabolism and reducing oxidative stress. Different types of tea have specific chemical compositions and can alleviate AAI. In conclusion, despite variations in the composition and mechanism of action, tea is a potent natural product to alleviate a hangover and protect the liver.

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Section: Introductionmentioning

confidence: 99%

Six Types of Tea Reduce Acute Alcoholism in Mice by Enhancing Ethanol Metabolism, Suppressing Oxidative Stress and Inflammation

et al. 2022

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“…Other CNS adverse effects have been reported. One rare side effect is optic neuritis [ 184 , 185 , 186 ], which is dose-related [ 184 ] and may resolve slowly over many months or be irreversible [ 186 ]. Disulfiram has also been associated with rare cases of fulminant encephalopathy and CNS abnormalities upon MRI [ 8 , 187 ]; both of these cases led to hospitalization and death from complications shortly thereafter.…”

Section: Resultsmentioning

confidence: 99%

Disulfiram: Mechanisms, Applications, and Challenges

et al. 2023

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Background: Since disulfiram’s discovery in the 1940s and its FDA approval for alcohol use disorder, other indications have been investigated. This review describes potential clinical applications, associated risks, and challenges. Methods: For this narrative review, a PubMed search was conducted for articles addressing in vivo studies of disulfiram with an emphasis on drug repurposing for the treatment of human diseases. The key search terms were “disulfiram” and “Antabuse”. Animal studies and in vitro studies highlighting important mechanisms and safety issues were also included. Results: In total, 196 sources addressing our research focus spanning 1948–2022 were selected for inclusion. In addition to alcohol use disorder, emerging data support a potential role for disulfiram in the treatment of other addictions (e.g., cocaine), infections (e.g., bacteria such as Staphylococcus aureus and Borrelia burgdorferi, viruses, parasites), inflammatory conditions, neurological diseases, and cancers. The side effects range from minor to life-threatening, with lower doses conveying less risk. Caution in human use is needed due to the considerable inter-subject variability in disulfiram pharmacokinetics. Conclusions: While disulfiram has promise as a “repurposed” agent in human disease, its risk profile is of concern. Animal studies and well-controlled clinical trials are needed to assess its safety and efficacy for non-alcohol-related indications.

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“…In line with the data from reported by Ahadome et al we also detected increased mRNA levels of different ALDH isoforms, including Aldh1b1 in MMP skin, which reinforces the role of the enzyme in fibrotic scarring. Disulfiram was initially approved for management of alcohol dependence and is currently evaluated for treatment of malignancies and fungal infections (58)(59)(60). The ALDH1 family was also shown to play a role in atopic dermatitis pathology, though its precise function in the skin and disease mechanisms are not yet understood (61).…”

Section: Discussionmentioning

confidence: 99%

Increased Fibrosis in a Mouse Model of Anti-Laminin 332 Mucous Membrane Pemphigoid Remains Unaltered by Inhibition of Aldehyde Dehydrogenase

et al. 2022

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Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by autoantibodies against the basal membrane zone of skin and surface-close epithelia and predominant mucosal lesions. The oral cavity and conjunctivae are most frequently affected, albeit clinical manifestations can also occur on the skin. MMP-associated lesions outside the oral cavity typically lead to scarring. Mechanisms underlying scarring are largely unknown in MMP and effective treatment options are limited. Herein, we assessed the collagen architecture in tissue samples of an antibody-transfer mouse model of anti-laminin-332 MMP. In MMP mice, increased collagen fibril density was observed in skin and conjunctival lesions compared to mice injected with normal rabbit IgG. The extracellular matrix of MMP skin samples also showed altered post-translational collagen cross-linking with increased levels of both lysine- and hydroxylysine-derived collagen crosslinks supporting the fibrotic phenotype in experimental MMP compared to control animals. In addition, we evaluated a potential anti-fibrotic therapy in experimental anti-laminin-332 MMP using disulfiram, an inhibitor of the aldehyde dehydrogenase (ALDH), which has been implicated in immune-mediated mucosal scarring. In addition, disulfiram also acts as a copper chelator that was shown to block lysyl oxidase activity, an enzyme involved in formation of collagen crosslinks. Topical use of disulfiram (300 μM in 2% [w/v] methocel) did not improve ocular lesions in experimental MMP over the 12-day treatment period in disulfiram-treated mice compared to vehicle-treated mice (n=8/group). Furthermore, C57BL6/J mice (n=8/group) were treated prophylactically with 200 mg/kg p.o. disulfiram or the solvent once daily over a period of 12 days. Systemic treatment did not show any reduction in the severity of oral and ocular lesions in MMP mice, albeit some improvement in skin lesions was observed in disulfiram- vs. vehicle-treated mice (p=0.052). No reduction in fibrosis was seen, as assessed by immunohistochemistry. Whilst blocking of ALDH failed to significantly ameliorate disease activity, our data provide new insight into fibrotic processes highlighting changes in the collagenous matrix and cross-linking patterns in IgG-mediated MMP.

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Advantages and disadvantages of disulfiram coadministered with popular addictive substances

Cited by 12 publications

References 81 publications

Six Types of Tea Reduce Acute Alcoholism in Mice by Enhancing Ethanol Metabolism, Suppressing Oxidative Stress and Inflammation

Six Types of Tea Reduce Acute Alcoholism in Mice by Enhancing Ethanol Metabolism, Suppressing Oxidative Stress and Inflammation

Disulfiram: Mechanisms, Applications, and Challenges

Increased Fibrosis in a Mouse Model of Anti-Laminin 332 Mucous Membrane Pemphigoid Remains Unaltered by Inhibition of Aldehyde Dehydrogenase

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