Comparative effects of Mancozeb and Disulfiram-induced striated muscle myopathies in Long-Evans rats

Stephenson, Olivia; Trombetta, Louis D.

doi:10.1016/j.etap.2019.103300

Cited by 9 publications

(5 citation statements)

References 25 publications

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“…One such side effect is myopathy. A study in mice found that disulfiram administration led to increased serum myoglobin and LDH, indicative of myocyte necrosis [ 188 ]. Disulfiram also caused elevations in cardiac troponin I, indicative of specific damage to the cardiac myocyte [ 188 ].…”

Section: Resultsmentioning

confidence: 99%

“…A study in mice found that disulfiram administration led to increased serum myoglobin and LDH, indicative of myocyte necrosis [ 188 ]. Disulfiram also caused elevations in cardiac troponin I, indicative of specific damage to the cardiac myocyte [ 188 ]. Beyond the commonly reported side effect of papular acne, other dermatologic side effects have been rarely reported.…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Disulfiram: Mechanisms, Applications, and Challenges

et al. 2023

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“…Based on the available reports, MCC950, an inhibitor of the NACHT domain of NLRP3, may exhibit adverse renal effects with the augmentation of renal inflammation and the emergence of glomerulosclerosis in diabetic individuals [ 161 ]. Disulfiram, a therapeutic agent targeting GSDMD, has rare side effects, including papular acne, pruritus, exfoliative dermatitis, myopathy, and cardiomyopathy [ 162 , 163 , 164 ]. Celastrol, an inhibitor of the ROS-NF-κB-NLRP3 inflammasome axis, may induce hepatotoxicity, ototoxicity, or cardiotoxicity [ 165 ].…”

Section: Therapeutic Potential By Targeting the Nlrp3 Inflammasomementioning

confidence: 99%

The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review

Chen,

Tang,

Chen

2024

IJMS

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Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by chronic synovitis and the progressive destruction of cartilage and bone. RA is commonly accompanied by extra-articular comorbidities. The pathogenesis of RA and its comorbidities is complex and not completely elucidated. The assembly of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activates caspase-1, which induces the maturation of interleukin (IL)-1β and IL-18 and leads to the cleavage of gasdermin D with promoting pyroptosis. Accumulative evidence indicates the pathogenic role of NLRP3 inflammasome signaling in RA and its comorbidities, including atherosclerotic cardiovascular disease, osteoporosis, and interstitial lung diseases. Although the available therapeutic agents are effective for RA treatment, their high cost and increased infection rate are causes for concern. Recent evidence revealed the components of the NLRP3 inflammasome as potential therapeutic targets in RA and its comorbidities. In this review, we searched the MEDLINE database using the PubMed interface and reviewed English-language literature on the NLRP3 inflammasome in RA and its comorbidities from 2000 to 2023. The current evidence reveals that the NLRP3 inflammasome contributes to the pathogenesis of RA and its comorbidities. Consequently, the components of the NLRP3 inflammasome signaling pathway represent promising therapeutic targets, and ongoing research might lead to the development of new, effective treatments for RA and its comorbidities.

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“…In a recent study, mancozeb’s estrogenic activity was demonstrated . A separate study revealed that mancozeb exposure in rats and rabbits within the concentration limit set by the US EPA induced spontaneous abortion, along with the development of thyroid symptoms . Elsewhere, dietary exposure of rats to mancozeb (10–1000 ppm) in a long-term (104-week) feeding study revealed its carcinogenic nature; however, such high residue concentrations cannot occur if good agricultural practices are followed.…”

Section: Toxicological Concernsmentioning

confidence: 99%