Μεταβολομική Ανάλυση δειγμάτων νεφρών από μύες με νεφρίτιδα επαγόμενη από συστηματικό ερυθηματώδη λύκο με τη χρήση φασματοσκοπίας Πυρηνικού Μαγνητικού Συντονισμού NMR

Postgraduate Thesis uoadl:2934076 100 Read counter

Unit:
Κατεύθυνση Φαρμακευτική Ανάλυση-Έλεγχος Ποιότητας
Library of the School of Science
Deposit date:
2021-02-02
Year:
2021
Author:
Tsiara Ioanna
Supervisors info:
Εμμανουήλ Μικρός, Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Ευάγγελος Γκίκας, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Original Title:
Μεταβολομική Ανάλυση δειγμάτων νεφρών από μύες με νεφρίτιδα επαγόμενη από συστηματικό ερυθηματώδη λύκο με τη χρήση φασματοσκοπίας Πυρηνικού Μαγνητικού Συντονισμού NMR
Languages:
Greek
Translated title:
Μεταβολομική Ανάλυση δειγμάτων νεφρών από μύες με νεφρίτιδα επαγόμενη από συστηματικό ερυθηματώδη λύκο με τη χρήση φασματοσκοπίας Πυρηνικού Μαγνητικού Συντονισμού NMR
Summary:
Systemic lupus erythematosus (SLE, lupus) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Lupus nephritis (LN) affects 40–70% of all SLE patients and is characterized by the glomerular deposition of immune complexes followed by recruitment of an inflammatory response. LN continues to be a major source of morbidity and mortality for SLE patients. Metabolism is considered to play a key role in autoimmune diseases. Metabolic changes in autoimmune diseases might be due to inflammation as well as being involved in autoimmune pathogenesis. The complex pathogenesis and heterogeneity of SLE poses many challenges in finding novel biomarkers for early diagnosis and monitoring of the disease. Our goal is to assess the metabolic changes of inbred mice that spontaneously develop a disease similar to human systemic lupus erythematosus. Furthermore, we aim to identify metabolites associated with renal function as potential biomarkers for early-/late-onset lupus nephritis. Female F1 hybrids of NZB × NZW (NZBxNZW/F1) were subjected to nephrectomy at 1, 3 and 6 months of age. Female B6 mice were used as healthy controls. The kidneys were homogenized and extracted. A non-targeted ¹H nuclear magnetic resonance (¹H NMR) based metabolomic approach was used to analyze the aqueous kidney extracts. At first, we performed a time series analysis on the samples of the F1 mice and then compared the lupus model with the healthy control group at the three different time points. Differential biomarker candidates were identified by using multivariate and univariate statistical analysis, and their diagnostic accuracy was evaluated. We observed significant differences in the metabolic profiles of SLE and healthy cohorts, and we were also able to distinguish between pre-puberty and nephritis stage of the lupus model. Our results demonstrate a disturbed amino acid metabolism, with α-amino acids downregulated in SLE, and alterations in glycerophospholipid metabolism. We also found decreased levels of choline and uridine in nephritis stage compared to pre-puberty stage. During the final trimester leading to nephritis we observed from univariate statistics that taurine, myo-inositol, ADP, ATP and NAD+ were downregulated. Our findings also suggest a perturbed energy metabolism and increased oxidative stress characterizing the disease.
Main subject category:
Science
Keywords:
SLE, lupus, ¹H NMR, metabolomics, kidney
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
151
Number of pages:
123
File:
File access is restricted until 2024-04-02.

Ioanna_Tsiara_Master.pdf
8 MB
File access is restricted until 2024-04-02.