Metabolomic analysis of colistin in mice samples: Application in plasma

Postgraduate Thesis uoadl:3260533 5 Read counter

Κατεύθυνση Φαρμακευτική Ανάλυση-Έλεγχος Ποιότητας
Library of the School of Science
Deposit date:
Kritikaki Maria
Supervisors info:
Γκίκας Ευάγγελος, Καθηγητής, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
Μεταβολομική ανάλυση κολιστίνης σε δείγματα μυών: Εφαρμογή σε πλάσμα
Translated title:
Metabolomic analysis of colistin in mice samples: Application in plasma
Colistin is a polypeptide antibiotic that effectively treats infections caused by multidrug resistant Gram-negative bacteria, but its clinical use is limited due to nephrotoxicity. The purpose of the present study was to identify biomarkers of colistin-induced nephrotoxicity and to further characterize the mechanisms underlying this process by analysing plasma metabolites using untargeted metabolomic approach. Specifically, the mice groups were given the usual clinically administered dose (1 mg/kg) as well as this dose increased by 50% (1,5 mg/kg), in order to investigate the possible toxicity due to a small increase in the dose. The statistical analysis showed that the administered action of colistin has a significant effect on mice metabolism. Despite the small increase, the statistical differentiation of the groups proves the significant effect of the drug also at the level of the circulatory system. The results were evaluated based on the initial score (>0.95) and on the fit score (>0.7). Some metabolites that were identified and found at different concentrations between the two groups, have already been associated with nephrotoxicity in the literature. The main mechanisms that appear to be affected by increased colistin concentrations and are responsible for the nephrotoxicity that appears as an adverse effect are increase in oxidative stress, increased metabolism of S-adenosylmethionine (SAM) to homocysteine, increased tryptophan metabolism, possible effect on galactose metabolism, reduction of fatty acid oxidation. Therefore, colistin is thought to affect metabolism in several directions, dysregulating more than one biological pathway and causing locally assessed damage to renal function.
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Other subject categories:
Health Sciences
metabolomics, colistin, plasma, nephrotoxicity, antibiotic
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