Deoxycholic Acid (ATX-101) for Reduction of Submental Fat

Dunican, Kaelen C; Patel, Dhiren

doi:10.1177/1060028016653966

Cited by 12 publications

(8 citation statements)

References 12 publications

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“…Firstly, DOC-nitrofuran combinations could be developed for topical applications, such as wound and burn dressings. In 2015, ATX-101 in which Deoxycholic Acid is the active ingredient was approved by the Food and Drug Administrations for reduction of submental fat at a subcutaneous injection dose as high as 10 mg/mL and a volume of up to 10 mL [32]. This concentration is much higher than that of DOC (2.5 mg/mL) required for observing the synergy between DOC and nitrofurans, indicating that DOC concentrations of less than 10 mg/mL could be used in the combination without a concern about the serious toxicity.…”

Section: Discussionmentioning

confidence: 99%

In vitro synergy between sodium deoxycholate and furazolidone against enterobacteria

Olivera

Spagnuolo

et al. 2020

BMC Microbiol

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Background: Antimicrobial combinations have been proven as a promising approach in the confrontation with multi-drug resistant bacterial pathogens. In the present study, we identify and characterize a synergistic interaction of broad-spectrum nitroreductase-activated prodrugs 5-nitrofurans, with a secondary bile salt, Sodium Deoxycholate (DOC) in growth inhibition and killing of enterobacteria. Results: Using checkerboard assay, we show that combination of nitrofuran furazolidone (FZ) and DOC generates a profound synergistic effect on growth inhibition in several enterobacterial species including Escherichia coli, Salmonella enterica, Citrobacter gillenii and Klebsiella pneumoniae. The Fractional Inhibitory Concentration Index (FICI) for DOC-FZ synergy ranges from 0.125 to 0.35 that remains unchanged in an ampicillin-resistant E. coli strain containing a β-lactamase-producing plasmid. Findings from the time-kill assay further highlight the synergy with respect to bacterial killing in E. coli and Salmonella. We further characterize the mechanism of synergy in E. coli K12, showing that disruption of the tolC or acrA genes that encode components of multidrug efflux pumps causes, respectively, a complete or partial loss, of the DOC-FZ synergy. This finding indicates the key role of TolC-associated efflux pumps in the DOC-FZ synergy. Overexpression of Nitric Oxide-detoxifying enzyme Hmp results in a threefold increase in FICI for DOC-FZ interaction, suggesting a role of nitric oxide in the synergy. We further demonstrate that DOC-FZ synergy is largely independent of NfsA and NfsB, the two major activation enzymes of the nitrofuran prodrugs. Conclusions: This study is to our knowledge the first report of nitrofuran-deoxycholate synergy against Gramnegative bacteria, offering potential applications in antimicrobial therapeutics. The mechanism of DOC-FZ synergy involves FZ-mediated inhibition of TolC-associated efflux pumps that normally remove DOC from bacterial cells. One possible route contributing to that effect is via FZ-mediated nitric oxide production.

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Section: Discussionmentioning

confidence: 99%

In vitro synergy between sodium deoxycholate and furazolidone against enterobacteria

Olivera

Spagnuolo

et al. 2020

BMC Microbiol

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“…Another mammalian bile compound in common use is the endogenous secondary bile acid 4 , which is derived from primary bile acids, such as chenodeoxycholic acid or cholic acid, following colonic microbe conversion. − It is one of the seven most common bile acids present within the human digestive system and acts as an emulsifier of ingested fat within the human intestine, as well as being commonly used as a solubilizing agent for lipophilic compounds, such as phosphatidylcholine. , 4 is the major constituent of the traditional Chinese medicine known as “Niu Huang” (derived from ox gallstones), while the synthetic form of 4 is also marketed in injections for cosmetic procedures to reduce localized fat accumulations . The chemical structure of 4 is 3α,12α-dihydroxy-5β-cholan-24-oic acid …”

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confidence: 99%

“…32,33 4 is the major constituent of the traditional Chinese medicine known as "Niu Huang" (derived from ox gallstones), while the synthetic form of 4 is also marketed in injections for cosmetic procedures to reduce localized fat accumulations. 33 The chemical structure of 4 is 3α,12α-dihydroxy-5β-cholan-24-oic acid. 34 Importantly, 4 has been described as a potent TGR5 receptor agonist.…”

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confidence: 99%

Marine Bile Natural Products as Agonists of the TGR5 Receptor

et al. 2021

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Agonism of the G protein-coupled bile acid receptor "Takeda G-protein receptor 5" (TGR5) aids in attenuating cholesterol accumulation due to atherosclerotic progression. Although mammalian bile compounds can activate TGR5, they are generally weak agonists, and more effective compounds need to be identified. In this study, two marine bile compounds (5β-scymnol and its sulfate) were compared with mammalian bile compounds deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) using an in vitro model of TGR5 agonism. The response profiles of human embryonic kidney 293 cells (HEK293) transfected to overexpress TGR5 (HEK293-TGR5) and incubated with subcytotoxic concentrations of test compounds were compared to nontransfected HEK293 control cells using the specific calcium-binding fluorophore Fura-2AM to measure intracellular calcium [Ca 2+ ] i release. Scymnol and scymnol sulfate caused a sustained increase in [Ca 2+ ] i within TGR5 cells only, which was abolished by a specific inhibitor for G αq protein (UBO-QIC). Sustained increases in [Ca 2+ ] i were seen in both cell types with DCA exposure; this was unaffected by UBO-QIC, indicating that TGR5 activation was not involved. Exposure to UDCA did not alter [Ca 2+ ] i , suggesting a lack of TGR5 bioactivity. These findings demonstrated that both scymnol and scymnol sulfate are novel agonists of TGR5 receptors, showing therapeutic potential for treating atherosclerosis.

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“…Detergentes iônicos como desoxicolato interrompem a integridade das membranas introduzindo seus grupos hidroxilas polares no núcleo hidrofóbico da bicamada, levando ao colapso da membrana em micelas mistas de fosfolipídeos e moléculas detergentes. 1,2 Fosfatidilcolina é um glicerofosfolipídeo que facilita a emulsificação das gorduras, permitindo absorção e transporte de gordura. O mecanismo de lise da gordura subcutânea pela fosfatidilcolina ainda é motivo de estudos.…”

Section: Tratamento Da Adiposidade Localizada Com Lipolíticosunclassified

Perda de definição do contorno do submento: correto diagnóstico e algoritmo de tratamento

Faria¹,

Vilela²,

Bastos³

et al. 2022

S&CD

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Perda de definição do contorno do submento: correto diagnóstico e algoritmo de tratamento Loss of definition of the submental contouring: correct diagnosis and treatment algorithm RESUMOA busca por procedimentos estéticos voltados para a perda de definição do submento é crescente. Um correto diagnóstico é imperativo para o sucesso do tratamento e redução das complicações. Adiposidade localizada, flacidez cutânea e perda da estrutura óssea são os principais achados. Um algoritmo de tratamento foi discutido nesta revisão, lembrando-se, claro, da possibilidade de tratamentos combinados e sequenciais para melhores resultados.

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Deoxycholic Acid (ATX-101) for Reduction of Submental Fat

Abstract: ATX-101 is the first pharmacological intervention approved for the reduction of SMF and offers an alternative to invasive measures to improve the submental profile and positively affect patient self-image.

Cited by 12 publications

References 12 publications

In vitro synergy between sodium deoxycholate and furazolidone against enterobacteria

In vitro synergy between sodium deoxycholate and furazolidone against enterobacteria

Marine Bile Natural Products as Agonists of the TGR5 Receptor

Perda de definição do contorno do submento: correto diagnóstico e algoritmo de tratamento

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