Nikotin toksisitesi üzerine seçici siklooksijenaz-2 inhibisyonunun etkisi
Effect of inhibition selective cyclooxygenase-2 on nicotine toxicity
Yazar: SONGÜL ÜNÜVAR
Danışman: PROF. GÖKNUR AKTAY
İnönü Üniversitesi / Sağlık Bilimleri Enstitüsü / Farmakoloji Ana Bilim Dalı
Derece: Yüksek Lisans, 2007
Konu: Eczacılık ve Farmakoloji = Pharmacy and Pharmacology
Dizin: Antioksidanlar = Antioxidants ; Eser elementler = Trace elements ; Lipid peroksidasyonu = Lipid peroxidation ; Nikotin = Nicotine

Özet:
Nikotinin, COX-2 enzimini indükleyerek, oksidatif stresi artırdıgı bilinmektedir.Bu bilgiye dayanarak seçici bir COX-2 inhibitörünün, siklooksijenaz (COX) yolagındaserbest radikal olusumunu baskılayabilecegini ve buna baglı olarak nikotintoksisitesinin önlenebilecegini veya azaltılabilecegini düsündük.Bu amaçla, TBARS, GSH ve T-SH ile doku ve serumda çinko ve bakırdagılımları degerlendirildi. Nikotin toksisitesi ve toksisite üzerine seçici COX-2inhibisyonunun etkisi incelendi.Tüm gruplar kontrol grubuyla karsılastırıldıgında:Kontrol grubuna göre; nikotin grubunun karaciger, akciger, böbrek, beyin vekalp TBARS düzeylerinde anlamlı ( p<0.001 ) bir artıs bulundu.Kontrol grubuna göre; nikotin grubunun karaciger, akciger, böbrek, beyin vekalp GSH düzeylerinde anlamlı (p<0.001) bir artıs bulundu.Kontrol grubuna göre; nikotin grubunun karaciger, akciger, böbrek, beyin ve TSHdüzeylerinde anlamlı (p<0.001), kalp dokusunda anlamlı olmayan bir artıs bulundu.Kontrol grubuna göre; nikotin grubunun karaciger (p<0.05), akciger (p<0.001)çinko düzeylerinde anlamlı bir artıs, böbrek, beyin ve kalp çinko düzeylerinde anlamlıolmayan (p>0.05) bir artıs bulundu.Kontrol grubuna göre; nikotin grubunun karaciger, böbrek, beyin bakırdüzeylerinde anlamlı olmayan bir artıs (p>0.05), akciger (p<0.01) ve kalp (p<0.05) bakırdüzeylerinde anlamlı bir artıs bulundu.Kontrol grubuna göre, nikotin grubunun serum çinko düzeylerinde anlamlı birartıs (p<0.001) bulundu.Nikotin grubuyla nikotin+selekoksib grubu karsılastırıldıgında:Nikotin grubuna göre nikotin+selekoksib grubunun karaciger, akciger, böbrek,beyin ve kalp TBARS düzeylerinde anlamlı (p<0.001) bir azalma bulundu.Nikotin grubuna göre nikotin+selekoksib grubunun karaciger(p<0.01), akciger,böbrek, beyin ve kalp GSH düzeylerinde anlamlı (p<0.001) bir azalma bulundu.Nikotin grubuna göre nikotin+selekoksib grubunun karaciger, böbrek, beyin veakciger dokularının T-SH düzeylerinde anlamlı (p<0.001) bir azalma bulundu. Kalpdokusunun T-SH düzeylerinde istatistiksel olarak anlamlı olmayan bir azalma bulundu.Nikotin grubuna göre nikotin+selekoksib grubunun karaciger (p<0.01), akciger(p<0.001), böbrek (p<0.01), beyin (p<0.001), kalp (p<0.001) çinko düzeylerinde anlamlıbir azalma bulundu.Nikotin grubuna göre nikotin+selekoksib grubunun karaciger (p<0.05), akciger(p<0.001), böbrek (p<0.01), kalp (p<0.001) bakır düzeylerinde anlamlı bir azalmabulundu. Beyin (p>0.05) bakır düzeylerinde anlamlı olmayan bir azalma bulundu.Nikotin grubuna göre nikotin+selekoksib grubunun serum çinko düzeylerindeanlamlı olmayan bir azalma (p>0.05) bulundu.Anahtar Kelimeler: Nikotin, Siklooksijenaz-2, Lipit peroksidasyon, Antioksidanetki, Eser elementler.

Abstract:
It is known that nicotine increases the oxidative stress, inducing COX-2 enzyme.With this knowledge, we thought that a selective COX-2 inhibitor could swage the freeradical constitution on the way of cycloxygenase and according to this, nicotine toxicitycould be prevented or decreased.With this aim, with TBARS-GSH and T-SH in tissue and serum, the distributionof zinc and copper were evaluated.The effect of nicotine toxicity and the effect of selective COX-2 on toxicity wereexamined.When all groups were compared to control groups;Considering control group, a significant increase( P?0.001) was found on theTBARS levels of liver, lung, kidney, brain nicotine group.Considering control group, a significant increase (p?0.001) was found on thelevels of liver, lung, kidney and heart GSH of nicotine group.Considering control group, a significant increase (p?0.001) was found on thelevels of liver, lung, kidney, brain, heart T-SH of nicotine group.Considering control group, a significant increase was found on the levels of liver(p?0.05), lung (p?0.001), zinc and a non-significant increase (P?0.05) was found on thelevels of kidney, brain, heart, zinc of nicotine group.Considering control group, a non-significant (P?0.05) increase on the levels ofliver (P?0.01) and heart (P?0.05), copper was found.Considering control group, a significant increase ( P?0.001) was found on thelevels of serum zinc.When nicotine group and celecoxibe groups were compared :Considering nicotine group, a significant decrease (P?0.001) was found on thelevels of liver, lung, kidney, brain and heart TBARS of nicotine + celecoxibe group.Considering nicotine group, a significant decrease (P<0.001) was found on thelevels of liver (P<0.01), lung, kidney, brain and heart GSH of nicotine + celecoxibegroup.Considering nicotine group, a significant (P<0.001) was found on the T-SH levelsof liver, kidney, brain tissues. A statistically significant decrease (P<0.001) was found onthe T-SH levels of lung and heart tissues.Considering nicotine group, a significant decrease was found on the levels of liver(P<0.01), lung (P<0.001), kidney (P<0.001), heart (P<0.001) zinc of nicotine celecoxibegroup.Considering nicotine group, on the levels of liver (P<0.05), lung (P<0.001), kidney(P<0.01), heart (P<0.001), copper, a significant level was found. A non-significantdecrease was found on the levels of brain (P>0.05) copper of nicotine + celecoxibe group.Considering nicotine group, a non-significant decrease was found on the serumzinc levels of nicotine + celecoxibe group.Keywords: Nicotine, Cyclooxygenase-2, Lipid peroxidation, Antioxidant effect,Trace elements