There are few examples of therapeutic treatments in chemically-induced toxicity compared to pretreatments that protect against chemical injury. Cystamine treatment 12 hours after carbon tetrachloride (CCl₄) was reported to have therapeutic effects on CCl₄-induced hepatic necrosis via an unknown mechanism. The objectives of this project were to develop. quantitative animal models to characterize cystamine treatment of chemically-induced hepatotoxicity and to use the models to investigate possible mechanisms of the therapeutic effect. Cystamine produced dose related therapeutic effects against both CCl₄ and galactosamine-induced hepatic necrosis in male Sprague-Dawley rats. The therapeutic effect on galactosamine-induced damage demonstrated that cystamine has therapeutic effects that are unrelated to inhibition of early biochemical events initiating damage. This was an important finding since cystamine pretreatment will prevent CCl₄-induced hepatic damage by inhibiting the bioactivation of CCl₄. Cystamine-induced hypothermia did not cause a delay in the appearance of maximal hepatic damage. Cystamine also did not stimulate hepatic protein synthesis in intoxicated rats. Although cystamine was reduced to cysteamine in the livers of galactosamine treated rats the hepatic sulfhydryl content was only transiently affected by cystamine. Cystamine did not reduce toxicant-induced hepatic calcium accumulation, despite the fact that the influx of extracellular calcium into toxicant damaged cells is considered by many to be an irreversible event causing cell death. Cystamine also did not alter subcellular calcium distribution in toxicant treated rats or enhance recovery of microsomal calcium sequestration in CCl₄ treated rats. Since cystamine is metabolized to cysteamine in vivo and cysteamine can chelate calcium the effect of chelating agents and cysteamine analogs on galactosamine-induced hepatic damage was tested. Therapeutic effects were observed for the calcium chelators EDTA and EGTA, agents with a chelating structure similar to cysteamine (ie. a free amine and a free sulfhydryl on adjacent carbons), or agents which may be metabolized t0 such structures. The results suggest that calcium chelation may be a mechanism of therapeutic action in chemically-induced hepatotoxicity. A reduction of free calcium concentration via chelation would explain reduced cytotoxic consequences of toxicant-induced hepatic calcium accumulation.

Thesis (Doctoral)--Eberhard-Karls-Universität zu Tübingen, 1934.

Thesis (Doctoral)--Eberhard-Karls-Universität zu Tübingen, 1934.

Thesis (M.S.)--Central Connecticut State University, 1999. / Thesis advisor: Carol A. Jones. " ... in partial fulfillment of the requirements for the degree of Master of Science in Chemistry." Includes bibliographical references (leaves 42-51).

Thesis (Ph. D.)--University of Washington, 1981. / Vita. Bibliography: leaves [135]-149.

Thesis (doctoral)--Universität Zürich, 1951. / Vita. Includes bibliographical references (p. 84-85).

Orientador: Ione Pellegatti Lemonica / Banca: João Lauro Viana de Camargo / Banca: Márcia Guimarães da Silva / Banca: Silvana Lima Górniak / Banca: Regiane Kawakami / Tese não possui um resumo geral, possue um resumo para cada capítulo / Resumo : O objetivo do presente estudo foi verificar, experimentalmente, o possível mecanismo pelo qual o extrato aquoso de Plectranthus barbatus (boldo-brasileiro), planta utilizada popularmente como abortiva, atua sobre o organismo materno ou sobre o desenvolvimento do concepto durante o período de pré-implantação, correlacionando sua ingestão com possíveis alterações no transporte e desenvolvimento embrionário ou com alterações hormonais maternas...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract : The present study was conducted to determine the possible mechanism by which the aqueous extract of Plectranthus barbatus (brazilian-boldo), a plant used popularly as abortive agent, can lead to early loss of pregnancy, correlating this possible effect with morphological alterations in the embryo, oviductal motility dysfunctions or maternal hormonal level modifications...(Complete abstract, access undermentioned electronic address) / Doutor

Made available in DSpace on 2014-06-11T19:33:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-08-24Bitstream added on 2014-06-13T18:45:06Z : No. of bitstreams: 1 alvarenga_cmd_dr_botfm_prot.pdf: 1786103 bytes, checksum: 14d9f0d294fb6c639b79eab0f8e823c6 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo do presente estudo foi verificar, experimentalmente, o possível mecanismo pelo qual o extrato aquoso de Plectranthus barbatus (boldo-brasileiro), planta utilizada popularmente como abortiva, atua sobre o organismo materno ou sobre o desenvolvimento do concepto durante o período de pré-implantação, correlacionando sua ingestão com possíveis alterações no transporte e desenvolvimento embrionário ou com alterações hormonais maternas... / The present study was conducted to determine the possible mechanism by which the aqueous extract of Plectranthus barbatus (brazilian-boldo), a plant used popularly as abortive agent, can lead to early loss of pregnancy, correlating this possible effect with morphological alterations in the embryo, oviductal motility dysfunctions or maternal hormonal level modifications...(Complete abstract, access undermentioned electronic address)