Action of Sodium Deoxycholate on Subcutaneous Human Tissue: Local and Systemic Effects

Odo, Marina Emiko Yagima; Cucé, Luiz Carlos; ODO, LÍLIAN MAYUMI; Natrielli, Andréa

doi:10.1111/j.1524-4725.2006.33036.x

Cited by 44 publications

(26 citation statements)

References 51 publications

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“…Thirdly, Fungizone is made up of 33% AmB and 66% deoxycholic acid, which is a detergent. When injected at a concentration of only 2.5% into subcutaneous tissues, deoxycholic acid causes intense pain, swelling, acute inflammatory lympho-mononuclear infiltration, adipocyte apoptosis with fat necrosis, intense phagocytosis of fat cells by subcutaneous tissue macrophages, and necrosis of small blood vessels[43,44]. Fourthly, the product monograph for Ambisome states that it can cause significant tissue inflammation when injected subcutaneously in both rats and man (i.e., accidental drug extravasation from an intravenous infusion).…”

Section: Methodsmentioning

confidence: 99%

Accelerated healing of cutaneous leishmaniasis in non-healing BALB/c mice using water soluble amphotericin B-polymethacrylic acid

Corware¹,

Harris²,

Teo³

et al. 2011

Biomaterials

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Cutaneous leishmaniasis (CL) is a neglected tropical disease that causes prominent skin scaring. No water soluble, non-toxic, short course and low cost treatment exists. We developed a new water soluble amphotericin B-polymethacrylic acid (AmB-PMA) using established and scalable chemistries. AmB-PMA was stable for 9 months during storage. In vitro, it was effective against Leishmania spp. promastigotes and amastigote infected macrophages. It was also less toxic and more effective than deoxycholate-AmB, and similar to liposomal AmB. Its in vivo activity was determined in both early and established CL lesion models of Leishmania major infection in genetically susceptible non-healing BALB/c mice. Intradermal AmB-PMA at a total dose of 18 mg of AmB/kg body weight led to rapid parasite killing and lesion healing. No toxicity was seen. No parasite relapse occurred after 80 days follow-up. Histological studies confirmed rapid parasite clearance from macrophages followed by accelerated fibroblast mediated tissue repair, regeneration and cure of the infection. Quantitative mRNA studies of the CL lesions showed that accelerated healing was associated with increased Tumor Necrosis Factor-α and Interferon-γ, and reduced Interleukin-10. These results suggest that a cost-effective AmB-PMA could be used to pharmacologically treat and immunotherapeutically accelerate the healing of CL lesions.

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Section: Methodsmentioning

confidence: 99%

Accelerated healing of cutaneous leishmaniasis in non-healing BALB/c mice using water soluble amphotericin B-polymethacrylic acid

Corware¹,

Harris²,

Teo³

et al. 2011

Biomaterials

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“…As a proprietary, synthetically derived, purified formulation of deoxycholic acid, ATX-101 causes localized adipocytolysis when injected into subcutaneous fat. Histologic evidence indicates that disruption of adipocyte membranes by deoxycholate/deoxycholic acid prompts a mild inflammatory tissue response, which is responsible for clearing the cellular debris through macrophage recruitment and subsequent phagocytosis [20–23]. …”

Section: Introductionmentioning

confidence: 99%

Results from a Pooled Analysis of Two European, Randomized, Placebo-Controlled, Phase 3 Studies of ATX-101 for the Pharmacologic Reduction of Excess Submental Fat

McDiarmid¹,

Ruiz²,

Lee

et al. 2014

Aesth Plast Surg

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BackgroundThe injectable adipocytolytic drug ATX-101 is the first nonsurgical treatment for the reduction of submental fat (SMF) to undergo comprehensive clinical evaluation. This study aimed to confirm the efficacy and safety of ATX-101 for SMF reduction through a post hoc pooled analysis of two large phase 3 studies.MethodsPatients with unwanted SMF were randomized to receive 1 or 2 mg/cm2 of ATX-101 or a placebo injected into their SMF during a maximum of four treatment sessions spaced approximately 28 days apart, with a 12-week follow-up period. The proportions of patients with reductions in SMF of one point or more on the Clinician-Reported SMF Rating Scale (CR-SMFRS) and the proportions of patients satisfied with the appearance of their face and chin [Subject Self-Rating Scale (SSRS) score ≥4] were reported overall and in subgroups. Other efficacy measures included improvements in the Patient-Reported SMF Rating Scale (PR-SMFRS), calliper measurements of SMF thickness, and assessment of skin laxity [Skin Laxity Rating Scale (SLRS)]. Adverse events and laboratory test results were recorded.ResultsSignificantly greater proportions of the patients had improvements in clinician-reported measures (≥1-point improvement in CR-SMFRS: 58.8 and 63.8 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, and 28.6 % of the placebo recipients; p < 0.001 for both ATX-101 doses vs. placebo) and patient-reported measures (≥1-point improvement in PR-SMFRS: 60.0 and 63.1 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, vs. 34.3 % of the placebo recipients; p < 0.001 for both), analyzed alone or in combination, with ATX-101 versus placebo. These improvements correlated moderately with patient satisfaction regarding face and chin appearance (SSRS score ≥4: 60.8 and 65.4 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, vs. 29.0 % of the placebo recipients; p < 0.001 for both). In this study, ATX-101 was effective irrespective of gender, age, or body mass index. Reduction in SMF with ATX-101 was confirmed by calliper measurements (p < 0.001 for both doses vs. placebo) and generally did not lead to worsening of skin laxity (SLRS improved or was unchanged: 91.3 and 90.5 % of the patients who received ATX-101 1 and 2 mg/cm2, respectively, and 91.6 % of the placebo recipients). Adverse events were mostly transient, mild to moderate in intensity, and localized to the treatment area.ConclusionThe findings show ATX-101 to be an effective and well-tolerated pharmacologic treatment for SMF reduction.Level of Evidence IThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

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“…Also, some recent studies suggest that DCA has some effect in lipo-destruction in vitro [17-20]. This remains a question to be addressed in future research.…”

Section: Discussionmentioning

confidence: 94%

The Effect of Phosphatidylcholine and Deoxycholate Compound Injections to the Localized Adipose Tissue: An Experimental Study with a Murine Model

Noh

Heo

2012

Arch Plast Surg

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BackgroundPhosphatidylcholine (PPC) and deoxycholate (DCA) compound has been recently used for the purpose of partial lipolysis and is valued for its efficacy and lower invasiveness compared to liposuction and dermolipectomy used previously. In this article, the authors discuss the efficacy of the PPC dissolved in DCA via an experimental rat study model, along with suggesting a useful animal experimental model for the study of adipose tissue and lipolysis.MethodsBilateral inguinal fat pads of an experimental rat were elevated with the deep inferior epigastric vessel as the sole vascular pedicle. Normal saline was injected on one side as a control group and a PPC and DCA compound was injected on the other side. After 4 days, the rats were euthanized for microscopic tissue examination. The pathology was scored by a semiquantitative system in 4 categories: normal fat amount, fat necrosis, inflammatory activity, and stage of fibrosis. A Wilcoxon signed-rank test powered by SPSS packet program was used for statistical analysis and to determine significance.ResultsMicroscopic examination was performed on the obtained samples, and the experimental data of all four categories showed significant histologic differences compared to the control group. All of the data also showed statistical significance by the Wilcoxon signedrank test (P<0.01).ConclusionsIn the inguinal fat pad rat model, the control group and the experimental group had a differed significantly in the amount of normal fat tissue, inflammation, necrosis, and fibrosis. We recommend the rat inguinal fat pad model used in this study, as it is likely to be useful in related research.

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Action of Sodium Deoxycholate on Subcutaneous Human Tissue: Local and Systemic Effects

Abstract: SD induces an inflammatory reaction in subcutaneous human fat and dose-dependent adipocyte lysis with acute pain and fibrosis. No systemic effects were detected. Further studies will establish the best dose-result ratio, frequency of application, and long-term safety.

Cited by 44 publications

References 51 publications

Accelerated healing of cutaneous leishmaniasis in non-healing BALB/c mice using water soluble amphotericin B-polymethacrylic acid

Accelerated healing of cutaneous leishmaniasis in non-healing BALB/c mice using water soluble amphotericin B-polymethacrylic acid

Results from a Pooled Analysis of Two European, Randomized, Placebo-Controlled, Phase 3 Studies of ATX-101 for the Pharmacologic Reduction of Excess Submental Fat

The Effect of Phosphatidylcholine and Deoxycholate Compound Injections to the Localized Adipose Tissue: An Experimental Study with a Murine Model

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