Diphenyl ditelluride effect on embryo/fetal development in mice: Interspecies differences

Roman, Silvane Souza; Nava, Alexandra; Favero, Alexandre M.; Weis, Simone Nardin; Zeni, Gilson; Rocha, João Batista Teixeira da; Nogueira, Cristina W.

doi:10.1016/j.tox.2006.11.070

Cited by 4 publications

(5 citation statements)

References 29 publications

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“…It is extremely toxic to rodents, causing marked neurotoxic effects in mice after acute or prolonged exposure [6,[9][10][11]. DPDT can also be teratogenic, causing various morphologic abnormalities in mice foetuses during development [12]. In addition, it produces renal and hepatic toxicity in rodents as well as haematological disorders in human beings [7,13].…”

mentioning

confidence: 99%

Diphenyl Ditelluride‐Induced Cell Cycle Arrest and Apoptosis: A Relation with Topoisomerase I Inhibition

Jorge

Oliveira

Filippi-Chiela

et al. 2014

Basic Clin Pharma Tox

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The diphenyl ditelluride (DPDT) is a prototype for the development of new biologically active molecules. In previous studies, DPDT showed an elevated cytotoxicity in Chinese hamster fibroblast (V79) cells but the mechanisms for reduction of cell viability still remain unknown. DPDT showed mutagenic properties by induction of frameshift mutations in bacterium Salmonella typhimurium and yeast Saccharomyces cerevisiae. This organotelluride also induced DNA strand breaks in V79 cells. In this work, we investigated the mechanism of DPDT cytotoxicity by evaluating the effects of this compound on cell cycle progression, apoptosis induction and topoisomerase I inhibition. Significant decrease of V79 cell viability after DPDT treatment was revealed by MTT assay. Morphological analysis showed induction of apoptosis and necrosis by DPDT in V79 cells. An increase of caspase 3/7 activity confirmed apoptosis induction. The cell cycle analysis showed an increase in the percentage of V79 cells in S phase and sub-G1 phase. The yeast strain deficient in topoisomerase I (Topo I) showed higher tolerance to DPDT compared with the isogenic wild-type strain, suggesting that the interaction with this enzyme could be involved in DPDT toxicity. The sensitivity to DPDT found in top3Δ strain indicates that yeast topoisomerase 3 (Top3p) could participate in the repair of DNA lesions induced by the DPDT. We also demonstrated that DPDT inhibits human DNA topoisomerase I (Topo I) activity by DNA relaxation assay. Therefore, our results suggest that the DPDT-induced cell cycle arrest and reduction in cell viability could be attributed to interaction with topoisomerase I enzyme.

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mentioning

confidence: 99%

Diphenyl Ditelluride‐Induced Cell Cycle Arrest and Apoptosis: A Relation with Topoisomerase I Inhibition

Jorge

Oliveira

Filippi-Chiela

et al. 2014

Basic Clin Pharma Tox

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“…It has been used in organic synthesis for a long time and in the last 15 years its toxicity and, particularly, neurotoxicity have been extensively studied. Indeed, developmental exposure to (PhTe) 2 is teratogenic [17, 19, 90] and has been associated with long-term behavioral and neurochemical changes in rats [20–22, 91]. However, the majority of those studies have investigated the phenomena involved in the toxicity of (PhTe) 2 , but the molecular mechanism(s) involved in (PhTe) 2 effects has (have) not been studied in detail.…”

Section: An Overview On the Neurotoxicity Of Diphenyl Ditelluridementioning

confidence: 99%

“…There are experimental points of evidence that (PhTe) 2 causes gestational and lactational toxicity [19, 90]. Considering the lipophilic character of this compound, we can suppose that it could cross the placental barrier during pregnancy and be excreted in milk after birth, like other hydrophobic toxicants, such as polychlorinated biphenyls [234].…”

Section: Gestational and Lactational Toxicity Of Diphenyl Ditellumentioning

confidence: 99%

“…High doses of (PhTe) 2 (0.12 mg/kg of body weight) can be teratogenic to rat and mice fetuses, causing malformations in fore- and hind-limbs, absent or short tail, subcutaneous blood clots, exophthalmia, hydrocephalus, and presence of exposed brain. However, the mice are less susceptible to toxic effects induced by (PhTe) 2 than the rats, suggesting a different developmental toxicity induced by (PhTe) 2 among species [19, 90]. …”

Section: Gestational and Lactational Toxicity Of Diphenyl Ditellumentioning

confidence: 99%

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Signaling Mechanisms and Disrupted Cytoskeleton in the Diphenyl Ditelluride Neurotoxicity

Pessoa-Pureur

Heimfarth

Rocha

2014

Oxidative Medicine and Cellular Longevity

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Evidence from our group supports that diphenyl ditelluride (PhTe)2 neurotoxicity depends on modulation of signaling pathways initiated at the plasma membrane. The (PhTe)2-evoked signal is transduced downstream of voltage-dependent Ca2+ channels (VDCC), N-methyl-D-aspartate receptors (NMDA), or metabotropic glutamate receptors activation via different kinase pathways (protein kinase A, phospholipase C/protein kinase C, mitogen-activated protein kinases (MAPKs), and Akt signaling pathway). Among the most relevant cues of misregulated signaling mechanisms evoked by (PhTe)2 is the cytoskeleton of neural cells. The in vivo and in vitro exposure to (PhTe)2 induce hyperphosphorylation/hypophosphorylation of neuronal and glial intermediate filament (IF) proteins (neurofilaments and glial fibrillary acidic protein, resp.) in different brain structures of young rats. Phosphorylation of IFs at specific sites modulates their association/disassociation and interferes with important physiological roles, such as axonal transport. Disrupted cytoskeleton is a crucial marker of neurodegeneration and is associated with reactive astrogliosis and apoptotic cell death. This review focuses the current knowledge and important results on the mechanisms of (PhTe)2 neurotoxicity with special emphasis on the cytoskeletal proteins and their differential regulation by kinases/phosphatases and Ca2+-mediated mechanisms in developmental rat brain. We propose that the disrupted cytoskeletal homeostasis could support brain damage provoked by this neurotoxicant.

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“…34 Outro ponto relevante, é a concentração administrada, pois dependendo da quantidade fornecida ao animal podem ocorrer alterações severas em proteínas do citoesqueleto, danos no córtex e hipocampo, 35 alterações na pele, fígado e rins. 36,37,38,39 Os compostos orgânicos e inorgânicos de telúrio exercem atividades biológicas específicas. Os organoteluretos e diorganoditeluretos apresentam, como principais ações, potente atividade antioxidante e atuam na mimetização enzimática.…”

Section: Propriedades Biológicas Atribuídas Aos Compostos De Telúriounclassified

Síntese, estudo de estabilidade, aplicação biológica e fluorescente de compostos hipervalentes de telúrio e de organoteluretos

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Orientador: Prof. Dr. João Valdir Comasseto (IQ-USP) Co-orientador: Prof. Dr. Alcindo A. Dos Santos (IQ-USP)iii Autorizo a reprodução e divulgação total ou parcial deste trabalho, por qualquer meio convencional ou eletrônico, para fins de estudo e pesquisa, desde que citada a fonte. Ficha Catalográfica elaborada eletronicamente pelo autor, utilizando o programa desenvolvido pela Seção Técnica de Informática do ICMC/USP e adaptado para a Divisão de Biblioteca e Documentação do Conjunto das Químicas da USP Bibliotecária responsável pela orientação de catalogação da publicação: Marlene Aparecida Vieira -CRB -8/5562 iv v Agradecimentos Aproveito esse espaço para agradecer as pessoas que foram imprescindíveis na minha formação até esse momento. Ao meu orientador e AMIGO Prof. Dr. João V. Comasseto o qual me concedeu a oportunidade de ver a química "com outros olhos". Agradeço muito pelo carinho, dedicação e pela confiança o qual foi de grande importância na minha formação tanto profissional quanto pessoal desde quando eu era aluno de iniciação científica na UFPR. Sempre lembrarei das nossas boas conversas acompanhadas sempre de uma boa bebida. Enfim, obrigado por tudo Comasseto. A minha amada noiva PRICILA que me apoiou em tudo desde o vestibuar. Não foi nada fácil ficar longe de você todo esse período. Mas você acreditou no meu sonho! Muito obrigado por fazer parte da minha vida. Aos meus pais Marcos e Elizabeth por sempre me apoiarem e me fazerem acreditar que somente o estudo pode mudar o nosso destino. Aos meus irmãos (Everton, Evelyn, Hellen, Henry) que sempre me ajudaram de uma forma ou de outra a chegar até aqui. Aos meus cunhados e cunhadas que sempre torceram pelo meu sucesso. Ao meu primeiro "orientador" e irmão, Jefferson (Jeff) que acreditou no meu potencial e me ensinou tudo que era possível. Obrigado por tudo Jeff. Ao Prof. Alcindo que considero como um AMIGO IRMÃO e que me acolheu em seu laboratório e me proporcionou o que há de melhor para que essa tese pudesse ser realizada. Muito obrigado pela oportunidade e pela confiança Alcindo. Aos meus queridos colegas e amigos de laboratótio (Antônio, Augusto, Marcão, Gisele, Victor, Mônica e as demais pessoas que passaram pelo lab). Aos meus queridos ICs (Mauro e Gabriela) o qual me deram a oportunidade de orientá-los. A dona Rosa pelos cafezinhos e o Alex pelas boas conversas e que sempre esteve disposto em me ajudar. Ao meu irmão de coração Marcos (ML) que sempre esteve disposto em me ajudar desde quando cheguei em São Paulo. Aos professores Ataualpa e Tiago do IQ-USP por contribuírem de forma decisiva nos estudos teóricos e de espectrometria de massas apresentados nessa tese. Ao meu amigo Rodrigo (Peta) que foi imprescindível para que esse trabalho acontecesse. Muito obrigado por compartilhar seu conhecimento. Agradeço ao IQ-USP por me proporcionar uma estrutura física e humana de excelente qualidade. Aos funcionários da secretaria, da central analítica e do almoxarifado que sempre auxiliaram da melhor forma. Agradeço a CAPES pela bolsa de estudos, sem o qu...

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Diphenyl ditelluride effect on embryo/fetal development in mice: Interspecies differences

Cited by 4 publications

References 29 publications

Diphenyl Ditelluride‐Induced Cell Cycle Arrest and Apoptosis: A Relation with Topoisomerase I Inhibition

Diphenyl Ditelluride‐Induced Cell Cycle Arrest and Apoptosis: A Relation with Topoisomerase I Inhibition

Signaling Mechanisms and Disrupted Cytoskeleton in the Diphenyl Ditelluride Neurotoxicity

Síntese, estudo de estabilidade, aplicação biológica e fluorescente de compostos hipervalentes de telúrio e de organoteluretos

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