Supervisors info:
Ευάγγελος Γκίκας Καθηγητής Τμήμα Χημείας ΕΚΠΑ,
Ντότσικα Ιωάννης Καθηγητής Τμήμα Χημείας ΕΚΠΑ,
Παντερή Ειρήνη Καθηγήτρια Τμήμα Χημείας ΕΚΠΑ
Summary:
Colistin is an antibiotic drug that was discovered in 1947 and was widely used in the 60s. It was abolished two decades later due to its toxicity, mainly nephrotoxicity and neurotoxicity. However, because of the increase of antimicrobial resistance, there has been a need to reuse drugs such as colistin but as a last resort in very burdened patient cases. In this work, a metabolomic study of the toxicity of colistin in mice liver samples is carried out, with the aim of investigating liver toxicity, for which there is no extensive literature and to identify metabolites that indicate its toxicity. For this purpose, an in-vivo experimental procedure was carried out in which mices were used as experimental animals. Mices were divided into three groups, 1) the reference group (control group), 2) the maximum non-toxic dose group, 1 mg/kg and 3) the toxic dose group, 1.5 mg/kg. In both groups a single dose was given. Then the livers of all groups was obtained, a metabolite extraction protocol was applied and their preparation was followed by UPLC-QTOFMS analysis in positive and negative ESI ionization. Peak picking was performed on the obtained spectra and multiparametric analysis was used to reveal statistically significant biomarkers. Finally, the chemical structures of the features were characterized using in silico fragmentation methods and relevant online libraries. Potential metabolomic pathways and targeted analysis of the spectra were performed to verify the existence of additional metabolites involved in the distinguished pathways, and the sex-related dose-response relationship of colistin toxicity was studied. Here let's briefly mention some conclusions.
Keywords:
metabolomics,omics,toxicity,mice,liver,antibiotics,QTOF,biomarkers
