Sibiul Medical nr 4_2007.p65

RezistenÆa poate fi parÆial explicatå printr–un efect
inhibitor al fumatului çi stresului oxidativ pe funcÆia
HDAC, astfel interferând cu acÆiunea antiinflamatorie a
CS. Intradevår existå o corelaÆie între activitatea HDAC
çi efectele supresive a CS pe eliberarea de citokine.Stresul
oxidativ çi nitrativ în BPOC,inactiveazå specific HDAC2,
ducând la CS rezistentå. Chiar çi la pacienÆii care au stopat
fumatul Cs–rezistenÆa persistå, continuând stresul
oxidativ.[36]Ultimele cercetåri aratå cå activitatea HDAC
poate fi restauratå prin doze mici de teofilinå, care astfel
poate determina reversia corticorezistenÆei în BPOC.
Aceste cercetåri ar putea conduce la noi abordåri
terapeutice ale bolilor inflamatorii pulmonare care sunt
greu de tratat.[37]
8. CONCLUZII
Stressul oxidativ çi inflamaÆia reprezinta
evenimentele majore implicate în patogeneza BPOC.
Speciile oxigen reactive direct sau prin produçii lor
de peroxidare joaca un rol esenÆial în accentuarea
inflamaÆiei prin activarea factorilor transcripÆionali ai
genelor proinflamatorii. Ca rezultat apare o sechestrare a
neutrofilelor în microcirculaÆia pulmonarå,inactivarea
oxidativå a antiproteazelor hipersecreÆia de mucus,
peroxidarea lipidelor membranei,respiraÆia mitocondrialå
çi agresiunea epiteliului alveolar urmatå de remodelarea
matricei extracelulare çi apoptozå. Stressul oxidativ este
implicat în mecanismul corticorezistenÆei în BPOC.
AntioxidanÆii care au o bunå biodisponibilitate sau
moleculele care au activitate enzimaticå antioxidantå pot
fi terapii care protejeazå impotriva agresiunii directe a
oxidanÆilor dar pot çi altera fundamental evenimentele
inflamatorii care stau la baza BPOC.In prezent cercetårile
sunt orientate spre înÆelegerea mecanismelor moleculare
ale intervenÆiei antioxidanÆilor asupra cåilor de semnalizare
a celulelor ROS –mediate (ROS–specii oxigen reactive),
çi inhibiÆia råspunsului inflamator, în vederea creerii de
noi agenÆi terapeutici antioxidanÆi eficienÆi în BPOC.
Dezvoltarea acestor noi antioxidanÆi este importantå pentru
monitorizarea biomarkerilor oxidativi çi inflamatori în
progresia çi dezvoltarea bolii.[2]
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