In vitro cytotoxicity of ticlopidine in Hep G2 and Caco 2 cell lines

• Autor(a) principal: Martins, Catarina Isabel da Silva
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/5107
• topic: Células Caco 2; Células Hep G2; Citotoxicidade; Hipericão; Ticlopidina; Domínio/Área Científica::Ciências Médicas::Ciências da Saúde::Ciências Farmacêuticas

The present dissertation is divided into 3 parts. In the Part I is described the research work conducted at the Health Sciences Research Center of the University of Beira Interior (CICS–UBI, Covilhã) with the aim of evaluating the cytotoxicity of ticlopidine and Hypericum perforatum extractin hepatic and intestinal epithelium cell lines. Ticlopidine is a prodrug mainly used in the prophylaxis of thromboembolic complications in patients with thromboembolic disease, especially if they are aspirin-intolerant. It is associated with multiple drug interactions, mostly via cytochrome P450 (CYP)-inhibition. H. perforatum has been widely used as an antidepressant, anti-inflammatory and antimicrobial agent, being considered, however, responsible for numerous herb-drug interactions due to the induction of CYP enzymes and P-glycoprotein expression. Given the predisposition of both these compounds to induce interactions when co-administered with other substances, it was considered relevant to study their cytotoxicity, alone and in combination, in hepatic – Hep G2 – and intestinal epithelium – Caco 2 – cell lines. The cells were incubated with various concentrations of ticlopidine and/or H. perforatum extract at various periods of time and the putative cytotoxicity induced by each incubation condition was assessed through cellular viability (MTT) assays. Overall, the results showed that ticlopidine may be cytotoxic in both Hep G2 and Caco 2 cells, depending on its concentration and period of incubation, and that the simultaneous incubation of cells with both the compounds promotes a similar pattern to that observed when cells are incubated with the extract alone and it is dose-, time- and cell line-dependent. The Part II refers to the hospital pharmacy internship performed at the Istituti Fisioterapici Ospedalieri, in Rome, between February 2nd and April 29th 2015. Finally, the Part III refers to the community pharmacy internship carried out in the Nunes Feijão Pharmacy, near Barreiro, between May 11th and August 10th 2015.