Logo do repositório
 
Publicação

Study of predictive biomarkers of manganese toxicity : control and prevention of neurotoxicity associated with parenteral nutrition

2014Tese de doutoramento Acesso restrito
Ver registo simples
dc.contributor.advisorSantos, Ana Paula Marreilha dos, 1957-por
dc.contributor.advisorBatoréu, Maria Camila Canteiro, 1948-por
dc.contributor.authorSantos, Dinamene Marques dos
dc.date.accessioned2014-03-24T16:05:40Z
dc.date.available2014-03-24T16:05:40Z
dc.date.issued2014
dc.descriptionTese de doutoramento, Farmácia (Toxicologia), Universidade de Lisboa, Faculdade de Farmácia, 2014por
dc.description.abstractMn is an essential element supplemented to patients receiving parenteral nutrition (PN), however repeated Mn supplementation may cause neurotoxicity. To prevent Mn-induced neurotoxicity, we studied the mechanism of Mn toxicity in brain, aiming to select biomarkers of neurotoxicity, using 2 in vivo assays with Wistar rats sub-acutely exposed to 4 or 8 doses of MnCl2 (25 mg/Kg). Treated rats showed an increase of biomarkers of oxidative stress, F2-isoprostanes (F2-IsoPs) and F4- neuroprostanes (F4-NPs), as well as biomarkers of neuroinflammation prostaglandin E2 (PGE2), cortical glial fibrillary acidic protein immunoreactivity (GFAP-ir) and tumor necrosis factor-α (TNF-α). On the other hand, Mn decreased acetylcholinesterase (AChE) activity in rat´s brain. The reversibility of the neurotoxic effects was evaluated with several biomarkers and neurobehavioral assays, being cortical GFAP the most persistent after Mn exposure. Whole blood (WB) and urine Mn were used as biomarkers of Mn exposure, although urinary Mn appears to reflect recent exposure, while WB Mn concentration closely correlates with Mn accumulation. Thus, both biomarkers were selected to biomonitor patients receiving Mn in PN. Biomarkers related to energy metabolism, in particular tricarboxylic acid (TCA) cycle organic acids and AChE activity in red blood cells (RBC) were negatively correlated with brain cortical GFAP-ir and brain Mn levels. The urinary TCA cycle organic acids and AChE activity in RBCs may be predictive biomarkers to biomonitor PN patients. In addition, two antioxidants tested in RBE4 cells exposed to Mn, evidence that 5-ASA has a greater efficacy in protecting these cells from Mn-induced cytotoxicity, compared with 4-PAS.eng
dc.description.provenanceSubmitted by amelia Janeiro (ajaneiro@reitoria.ul.pt) on 2014-03-24T15:29:18Z No. of bitstreams: 1 ulsd067880_td_Dinamene_Santos.pdf.pdf: 2543497 bytes, checksum: 65e85157a60884e1bcb71070fd77c7b8 (MD5)eng
dc.description.provenanceMade available in DSpace on 2014-03-24T16:05:40Z (GMT). No. of bitstreams: 1 ulsd067880_td_Dinamene_Santos.pdf.pdf: 2543497 bytes, checksum: 65e85157a60884e1bcb71070fd77c7b8 (MD5)eng
dc.description.sponsorshipFundação para a Ciência e Tecnologia (FCT, SFRH/BD/64128/2009, Strategic Project Pest-OE/SAU/UI4013/2011)por
dc.identifier.tid101305800
dc.identifier.urihttp://hdl.handle.net/10451/10779
dc.language.isoengeng
dc.subjectTeses de doutoramento - 2014por
dc.titleStudy of predictive biomarkers of manganese toxicity : control and prevention of neurotoxicity associated with parenteral nutritioneng
dc.typedoctoral thesis
dspace.entity.typePublication
rcaap.contributor.authoremailrepositorio@reitoria.ulisboa.pt
rcaap.rightsembargoedAccesseng
rcaap.typedoctoralThesiseng

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura indisponível
Nome:
ulsd067880_td_Dinamene_Santos.pdf
Tamanho:
2.43 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções