Dithiocarbamates have a common toxic effect on zebrafish body axis formation

Tilton, Fred; Du, Jane La; Vue, Meng; Alzarban, Noor; Tanguay, Robert L.

doi:10.1016/j.taap.2006.04.014

Cited by 81 publications

(59 citation statements)

References 43 publications

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“…The Leishmania species infecting macrophages may therefore affect the toxicity profile of a particular compound on the host cell. Compounds 5455 and 3117 are also known teratogens (37,39). Considering the latter point, it is difficult to imagine a scenario where these dithiocarbamates would present an improvement over miltefosine for the systemic treatment of either VL or diffuse CL.…”

Section: Discussionmentioning

confidence: 99%

Identification of New Antileishmanial Leads from Hits Obtained by High-Throughput Screening

Zhu

Pandharkar

Werbovetz

2012

Antimicrob Agents Chemother

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A previous screen of ϳ200,000 compounds from the PubChem database identified 70 compounds possessing 50% effective concentrations (EC 50 s) below 1 M against Leishmania major promastigotes that were not toxic to mammalian epithelial cancer cells at this concentration (E. Combinations of existing antileishmanial drugs have also been studied. Different combinations of treatment with single-dose liposomal amphotericin B followed by short courses of miltefosine were extremely effective, with a single dose of liposomal amphotericin B at 5 mg/kg of body weight followed by a 10-day course of miltefosine resulting in a cure rate of 98% (32). This combination was evaluated together with other combinations consisting of (i) a single dose of 5 mg/kg liposomal amphotericin with a 10-day course of paromomycin and (ii) a 10-day course of both paromomycin and miltefosine, with all of these combinations providing a cure rate of 97% or greater (33). When given in a single 10 mg/kg dose, liposomal amphotericin B was shown to be highly effective against VL, producing a cure rate of 95.7% (30). Single-dose liposomal amphotericin B is proposed to play a central role in a VL elimination program in India, Nepal, and Bangladesh (12).SharlowDespite these improvements in VL treatment on the Indian subcontinent, unmet needs in leishmaniasis chemotherapy still exist. In Africa, only the antimonial drug sodium stibogluconate and liposomal amphotericin B are registered for treating VL. Antimonial compounds, which have been replaced by the drugs listed above for treating VL on the Indian subcontinent due to widespread antimonial resistance (31), have been used for many years against leishmaniasis, and their use is plagued by the long duration of therapy and by the associated side effects (15,18,23,31). Liposomal amphotericin B appears to be less effective against VL in Brazil (1) and in Africa (1, 14, 26) compared to India, and the expense of liposomal amphotericin B also limits its widespread use (9). Paromomycin is inexpensive and is thus a good candidate for VL treatment in African countries, but a 15 mg/kg/day regimen of paramomycin for 21 days was inferior to standard treatment with sodium stibogluconate (20 mg/kg

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Section: Discussionmentioning

confidence: 99%

Identification of New Antileishmanial Leads from Hits Obtained by High-Throughput Screening

Zhu

Pandharkar

Werbovetz

2012

Antimicrob Agents Chemother

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“…Cost, labor, time and infrastructure requirements can be significantly reduced by replacing the traditional rodent model with the embryonic zebrafish model. Embryonic zebrafish are a well-established model for studying basic developmental biological processes (reviewed in 11) and for toxicological assessments [12][13][14]. Zebrafish are vertebrates that share many cellular, anatomical and physiological characteristics with other vertebrates.…”

Section: Introductionmentioning

confidence: 99%

In vivo evaluation of carbon fullerene toxicity using embryonic zebrafish

Usenko

Harper

Tanguay

2007

Carbon

276

155

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There is a pressing need to develop rapid whole animal-based testing assays to assess the potential toxicity of engineered nanomaterials. To meet this challenge, the embryonic zebrafish model was employed to determine the toxicity of fullerenes. Embryonic zebrafish were exposed to graded concentrations of fullerenes [C 60 , C 70 , and C 60 (OH) 24 ] during early embryogenesis and the resulting morphological and cellular responses were defined. Exposure to 200 μg/L C 60 and C 70 induced a significant increased in malformations, pericardial edema, and mortality; while the response to C 60 (OH) 24 exposure was less pronounced at concentrations an order of magnitude higher. Exposure to C 60 induced both necrotic and apoptotic cellular death throughout the embryo. While C 60 (OH) 24 induced an increase in embryonic cellular death, it did not induce apoptosis. Our findings concur with results obtained in other models indicating that C 60 (OH) 24 is significantly less toxic than C 60 . These studies also suggest that that the embryonic zebrafish model is well-suited for the rapid assessment of nanomaterial toxicity.

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“…Studies on the effects of DTC on developing rat embryos show that these agents induce cleft palate, wavy rib formation, and long bone distortions (Roll, 1971). Several recent studies have shown sodium metam, thiram, and disulfiram caused notochord distortions, and craniofacial abnormalities in zebra fish embryos (Haendel et al, 2004;Tilton, et al, 2006;Teraoka et al, 2006;van Boxtel et al, 2010). Some effects of these chemicals on craniofacial malformation are attributed to their down-regulating effects on genes related to transforming growth factor beta-1 (TGF-1) which plays an important role in skeletal morphogenesis.…”

Section: Carcinogenic and Teratogenic Effectsmentioning

confidence: 99%