Radyoterapiye bağlı kardiyak hasarın önlenmesinde amifostin ve melatoninin etkileri
Effects of amifostine and melatonin in the prevention of radiotherapy-induced cardiac damage
Yazar: ZÜMRÜT BAHAT
Danışman: PROF. DR. MELEK NUR YAVUZ
Karadeniz Teknik Üniversitesi / Tıp Fakültesi / Radyoloji Onkolojisi Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2004
Konu: Radyasyon Onkolojisi = Radiation Oncology
Dizin: Radyasyon dozajı = Radiation dosage ; Radyasyon toleransı = Radiation tolerance

Özet:
RT'ye bagh kardiyak hasar iyi bilinen bir klinik durumdur. Serbest radikalleri
temizleyen bir radyoprotekt6r olan amifostinin normal hlicreleri iyonizan
radyasyondan korudugu bir 9ok dokuda gosterilmi~tir. Kronik donemde de
amifostinin kardiyoprotekt6r etkisi gosterilmi~tir. Bir diger serbest radikal
temizleyicisi olan melatonin de normal hi.icreleri iyonizan radyasyondan korudugu
kalp hari9 bir 9ok dokuda gosterilmi~tir. Bu 9ah~manm amac1 amifostin ve
melatoninin radyasyona baglt akut kardiyak hasara kar~t kardiyoprotekt6r etkisini
degerlendirmektir.
S19an kalpleri: 1. kardiyak fonksiyonlar, 2. oksidatif hasann biyokimyasal
belirteci, 3. patolojik degi~iklikler a91smdan incelenerek ger9ekle~tirildi. S19anlar
her grupta alt1 s19an olacak ~ekilde alt1 gruba aynld1. Grup 1'e 10 mg/kg melatonin,
grup 2'ye 200 mg/kg amifostin, grup 3'e serum fizyolojik enjekte edildi. Simlilasyon
yapild1ktan sonra, grup I, 2 ve 3'e enjeksiyonu takip eden 30 dak. i9inde 20 Gy
kardiyak RT tek fraksiyoncla uyguland1. Grup 4' e I0 mg/kg melatonin , grup 5'e
200 mg/kg arnifostin, grup 6'ya serum fizyolojik enjekte edildi. Ancak simlilasyon
yapild1ktan sonra, grup 4, 5 ve 6'ya enjeksiyonu takiben kardiyak RT31
uygulanmayarak, kontrol grup\an olarak b1rakt!dilar. Kardiyak fonksiyonlan
degerlendirmek i9in Langendorff perflize s19an kalbi metodu uygulandt. Kalp h1z1,
koroner sistolik ve diyastolik basm9lar ol9illdU. Sempatomimetik uyaran olan
izoproterenol enjeksiyonunu takiben kalp h1z1, koroner sistolik ve diyastolik
basm9lar tekrar ol9Uldil Oksidatif hasara bagh biyokimyasal belirteci
degerlendirmek i9in s19anlarm kalp dokusunda bulunan MDA degerleri ol9illdil.
Patolojik degi~iklikleri incelemek i9in s19an kalp dokusu 1~1k mikroskobu ve elektron
mikroskobu ile degerlendirildi.
Sempatomimetik uyaran izoproterenole bagh artan kalp h1z1 RT sebebiyle, KG
degerlerine gore dU~Ukti.i. I~1k mikroskobunda ise fokal perikardiyal iltihap
alanlanna rastland1. Ancak RT sonras1 kalp h1z1, koroner sistolik ve diyastolik
bas1119lar, sempatomimetik uyaran izoproterenol enjeksiyonu sonras1 koroner sistolik
ve diyastolik bas1119lar, MDA degerleri, elektron mikroskop degerlendirilmesi
degi~medi. RT fincesi amifostin uygulanmas1 izoproterenole enjeksiyonu sonras1
kalp h1zmdaki RT'ye bagh dli~meyi ve 1~1k mikroskobunda gozlenen fokal
perikardiyal iltihap alanlarma rastlanmas1111 degi~tirmedi. RT oncesi melatonin
uygulanmas1 1~1k mikroskobunda gozlenen fokal perikardiyal iltihap alanlanna
rastlanmasm1 degi~tirmedi. Ama RT oncesi melatonin uygulanmas1yla
sempatomimetik uyaran izoproterenol sonras1 artan kalp h1z111da RT nedeniyle
dii~me olmad1.
Bu 9ah~ma sonucunda RT oncesi uygulanan amifostinin akut kardiyak hasan
engellemedigi ancak melatonin uygulamasmm kardiyak hasan onleyebilecegi
dii~Unillmektedir.

Abstract:
Radiation induced cardiac injury is well known clinical entity. The
radioprotectant free-radical scavenger amifostine has been demostrated to protect
normal cells from ionizing radiation in many tissues. In chronic phase,
cardioprotective effects of amifostine has been demostrated as well. The another
free-radical scavenger melatonin has been demostrated to protect normal cells from
ionizing radiation in many tissues also, but cardiac tissue. The aim of this study was
to investigate the acute cardioprotective effects of amifostine and melatonin against
radiation induced cardiac injury.
We evaluated heart of rat: 1. cardiac functional change, 2. biochemical
determination of oxidative damage, 3. pathological changes. Rats were divided into
six grups that each grup containing six rats. Group 1 was injected 10 mg/kg of
melatonin, group 2 was injected 200 mg/kg of amifostine, group 3 was injected
sodium chloride 0.9%. After simulation, following a 30 min-period 20 Gy cardiac
irradiation was given to groups 1, 2 and 3 in single fraction. Group 4 was injected 1033
mg/kg of melatonin, group 5 was injected 200 mg/kg of amifostine, group 6 was
injected sodium chloride 0.9%. But after simulation, cardiac irradiation was not
given to groups 4, 5 and 6 and they are reserved as control groups. To evaluate
cardiac fuctional change, method of Langendorff perfused rat heart is performed.
Heart rate, coranary systolic and diastolic pressures were measured. Following
isoproterenol injection as a sympathomimetic stimulant, heart rate, coranary systolic
and diastolic pressures were measured again. To evaluate biochemical determination
of oxidative damage, MDA was measured in cardiac tissue of rats. To evaluate
pathological changes, cardiac tissue of rats were examined by light microscope and
electron-microscope.
RT resulted in decrease of increased heart rate by sympathomimetic stimulant
isoproterenol injection and pericardia) focal inflamation areas in hearts of rat by light
microscope according to KG. But RT did not result changes at heart rate, coronary
systolic and diastolic pressures, coronary systolic and diastolic pressures by
sympathomimetic stimulant isoproterenol injection, MDA levels, electron
microscopic evaluation. Amifostine administration prior to RT not changed m
decrease of increased heart rate by isoproterenol injection and evaluation of
pericardia! focal inflamation areas in hearts of rat by light microscope. Melatonin
administration prior to RT not changed in evaluation of pericardia! focal inflamation
areas in hearts of rats by light microscope as well. However there was not decrease
of increased heart rate by sympathomimetic stimulant isoproterenol injection caused
by RT that were pretreated with melatonin.
The data obtained in this study suggest that amifostine administration prior to RT
not prevent cardiac damage, but melatonin administration prior to RT may be
beneficial to prevent cardiac damage.