Asistent Medicinskog fakulteta, Katedra Hemija, mr Radmila
Pavlović uspešno je završila doktorske studije na biohemijskom odseku
Državnog Univerziteta u Milanu, Italija. Doktorsku disertaciju pod naslovom
"Oxidative and nitrative stress in pathological events: role
of selected biomarkers and related analytical studies"
13.12.2007. godine i stekla akademski naziv doktor biohemijskih nauka.
UNIVERSITA’ DEGLI STUDI DI MILANO
di Medicina e Chirurgia
Dipartimento di Medicina, Chirurgia e Odontoiatria
Paolo - Polo Universitario,
Dottorato di Ricerca in Biochimica
XX Ciclo, BIO/10
OXIDATIVE AND NITRATIVE STRESS IN
PATHOLOGICAL EVENTS: ROLE OF SELECTED
BIOMARKERS AND RELATED ANALYTICAL STUDIES
Coordinatore del dottorato: Prof.ssa Silvia PAGANI
Anno Accademico 2006/2007.
Aim of study was to
evaluate different biomarkers for non-invasive measurement of oxidative/nitrative
stress. The nitric oxide (NO) pathway was studied by assaying the arginines
profile (L-arg, asymmetric dimethylarginine - ADMA, symmetric
dimethylarginine – SDMA) in patients from Intensive Care Unit (ICU). ADMA is
an endogenous non selective inhibitor of NO synthase while SDMA competes
with L-arg for cellular transport. Dimethylarginines (DMA) and nitrate level
as well as variety of biochemical and clinical parameters were determined
after patients enrolment and during ICU stay. Obtained results suggests that
DMA could have a metabolic role tightly related to the development of
systemic inflammatory reaction. High DMA levels demonstrates an impaired L-arginine/NO
pathway and could promote oxidative stress
development. The possibility that DMA may not only indicate risk but rather
contribute to adverse events actually opens new therapeutic perspectives.
Contemporary, another biomarker of
oxidative/nitrative stress has been studied that is 3-nitrotyrosnine (NY).
Up to now, there is no consensus on its basal levels, or on its biological
significance. Therefore, a new, gas chromatography–electron capture detector
method for plasma free NY has been developed. This new approach provides a
readily applicable method for study of the role NY during oxidative/nitrative
stress development. Furthermore, there is increasing evidence that carbonyl
compounds, and in particular 4-hydroxy-2-nonenal (HNE) generated
endogenously during the oxidative degradation of lipids, is involved in the
onset and progression of many pathologies. Therefore we have synthesied
4-hydroxy-2-nonenal dimethylacetal (HNE-DMA) as source of HNE. The synthetic
procedure for the preparation of HNE-DMA was adapted to the preparation of a
deuterated isotopomer. In this way, a labeled compound could constitute a
suitable internal standard for gas chromatography-mass spectrometry (GC-MS)
analysis of suitable HNE derivatives.