Uticaj terapije radioaktivnim jodom 131I na hematološke parametre i antioksidativni status pacijenata sa diferentovanim karcinomom štitaste žlezde
The effect of radioactive iodine therapy 131I on the haematological parameters and the antioxidant status of patients with differentiated thyroid carcinoma
Докторанд
Spasojević-Tišma, VeraМентор
Todorović, AnaЧланови комисије
Mihaljević, Olgica B.Pejić, Snežana
Srejović, Ivan M.
Метаподаци
Приказ свих података о дисертацијиСажетак
Maligni tumori štitaste žlezde predstavljaju 95% slučajeva svih dijagnostikovanih
karcinoma endokrinog sistema. Godišnja stopa incidence u različitim delovima sveta se
kreće od 0,5-10 slučajeva na 100,000 stanovnika, a u Srbiji broj novoobolelih iznosi 1,6
muškaraca i 5,8 žena na 100,000 stanovnika na godišnjem nivou.
Terapijska primena radioaktivnog joda (131I) radi ablacije postoperativno
preostalog tkiva štitaste žlezde i jodavidnih metastaza je deo standardne procedure
lečenja obolelih od diferentovanih tireoidnih karcinoma (DTC). Terapija 131I, iako
relativno bezbedna, nosi izvestan rizik od pojave neželjenih efekata koji su posledica
radijacionog oštećenja zdravih tkiva i organa, među kojima su kostna srž i periferna krv.
Cilj ove studije je da se kod pacijenata sa DTC ispitaju hematološki parametri (nivo
leukocita, eritrocita, trombocita, hemoglobina i hematokrita), parametri oksidativnog
stresa (aktivnosti antioksidativnih enzima, koncentracija reaktivnih kiseoničnih... vrsta i
intenzitet lipidne peroksidacije) pre i nakon aplikacije velikih doza radioaktivnog 131I
(3,70 i 5,55 GBq). Takođe, cilj studije je bio i da se dobijene vrednosti analiziraju u odnosu
na dozu aplikovanog 131I i vreme proteklo od njegove primene (3, 7 i 30 dana nakon terapije).
Istraživanjem je obuhvaćeno 68 pacijenata oba pola, kojima je urađena tireoidektomija,
postavljena dijagnoza dobro diferentovanog karcinoma štitaste žlezde i apliciran 131I u
dozi od 3,70 ili 5,55 GBq. Dobijeni rezultati ukazuju da terapija bilo kojom od ispitivanih
doza 131I dovodi do smanjenja svih hematoloških parametara u posmatranim vremenskim
tačkama u odnosu na vrednost pre terapije. Obe ablacione doze 131I indukuju povećanje
oksidativnog stresa koje se ogleda u povećanju nivoa TBARS-a, i t o u 3 . i 7 . d anu n akon
primene doze od 3,70 GBq, a u 3. i 30. danu nakon doze od 5,55 GBq. Terapija 131I kod pacijenata
sa DTC indukuje i promene vrednosti AO parametara. Aktivnost SOD nakon primene 131I u dozi
od 3,70 GBq značajno je povećana 3. i 30. dana, a nakon primene 131I od 5,55 GBq 3. i 7. dana u
odnosu na vrednost pre terapije. Nakon doze od 3,70 GBq aktivnost CAT pokazuje sniženje 30.
dana, dok doza 131I od 5,55 GBq povećava aktivnost CAT 7. dana u odnosu na 0. dan. Obe doze 131I
dovode do značajnog porasta vrednosti GSH 7. dana, dok samo doza od 5,55 GBq dovodi do
sniženja GSH 30. dana u odnosu na 0. dan. 131I indukuje značajne promene nivoa slobodnih
radikala u krvi DTC pacijenata. Terapija 131I u dozi od 5,55 GBq povećava nivo O2
.- samo u 30.
danu, dok vrednosti O2
.- nakon primene doze od 3,70 GBq nisu značajno promenjene u odnosu
na 0. dan. Nivo H2O2 u krvi DTC pacijenata je snižen 7. i 30. dana nakon primene doze od 3,70
GBq, a ne menja se značajno ni nakon primene doze od 5.55 GBq. Nijedna od ispitivanih doza
131I ne indukuje statistički značajnu promenu vrednosti .NO u odnosu na nivo pre terapije.
Analiza korelisanosti TBARS-a i hematoloških parametara je pokazala da je TBARS
negativno korelisan sa Hgb i Hct. Analizom korelisanosti enzima i njihovih supstrata
utvrđeno je da je aktivnost SOD pozitivno korelisana sa nivoom O2
.- samo 30. dana nakon
primene doze od 5.55 GBq. Aktivnost CAT je negativno korelisana sa H2O2 u svim posmatranim
vremenskim tačkama nakon doze od 3,70 GBq 131I, a n akon d oze o d 5.55 GBq samo 30. dana.
Rezultati multiple linearne regresije su pokazali da od pet testiranih parametara (SOD,
CAT, GSH, O2
.-, H2O2 i .NO) samo aktivnost SOD i koncentracije H2O2 i O2
.- značajno utiču na
nivo TBARS-a u krvi DTC pacijenata.
Rezultati ove studije ukazuju da terapija 131I indukuje povećanje oksidativnog stresa,
koje se ogleda u povećanju nivoa TBARS-a, ali i u narušenom balansu enzimskih i
neenzimskih komponenti antioksidativne zaštite i produkcije slobodnih radikala koji
mogu imati značajan uticaj na kasnije efekte terapije 131I.
Malignant tumors of the thyroid gland represent 95% of all diagnosed endocrine cancers. The annual
incidence rate ranges from 0.5 to 10 cases per 100 000 inhabitants, and in Serbia this incidence is 1.6
men and 5.8 women per 100 000.
Therapeutic use of radioactive iodine (131I) for the ablation of postoperatively residual thyroid tissue
and iodine metastases is part of the standard procedure for patients with differentiated thyroid
carcinoma (DTC). Although treatment is tolerated well by most patients adverse effects of DTC
treatment have been increasingly recognized, and are reason for a debate on the required
aggressiveness of DTC treatment. Adverse effects result from radiation damage of the healthy
tissues and organs, including bone marrow and peripheral blood.
This study included 68 patients of both sexes who were diagnosed with DTC, underwent
thyroidectomy, and were treated with fixed doses of 3.70 or 5.55 GBq of 131I. The aim of the study
was to investigate hematologi...c parameters (leukocyte, erythrocyte, platelet, hemoglobin and
hematocrit levels) as well as oxidative stress parameters (antioxidant enzymes activity, levels of
reactive oxygen species and lipid peroxidation ) their correlation and significance for lipid
peroxidation in blood of DTC patients 0, 3, 7 and 30 days after therapy. The obtained results
indicate that compared to the pre-therapy values in the 3rd, 7th and 30th day after radiotherapy both
of the examined 131I doses a decrease in all hematological parameters. TBARS level was elevated in
3rd and 7th day after a dose of 3.70 GBq, and in 3rd and 30th day after exposure to dose of 5,55 GBq.
Following dose of 3.70 GBq the SOD activity was significantly increased in the 3rd and 30th days, and
after the application of 5.55 GBq in the 3rd and 7th days after therapy. Activity of CAT was decreased
in 30th day after a dose of 3.70 GBq, while a dose 5.55 GBq increased CAT activity only in 7th day
compared to day 0. Both doses of 131I led to a significant increase in GSH values in 7th day, while
only a dose of 5.55 GBq induced a GSH reduction in 30th day after radiotherapy. As regards the level
of free radicals, therapy with 5.55 GBq of 131I increased the level O2
.- only in 30th days, while
administration of 3.70 GBq did not change the O2
.- level in any of the examined time points. The H2O2
level in the blood of the DTC patients was decreased in 7th and 30th day after a dose of 3.70 GBq, and
it was not changed significantly following the dose of 5.55 GBq. None of the examined 131I doses
induced a significant change in .NO value compared to its pre-treatment level.
The correlation analysis of TBARS and hematological parameters showed that TBARS was negatively
correlated with Hgb and Hct. Regarding enzymes activity and levels of their substrates it was found
that SOD correlated with the O2
.- only in 30th day after a dose of 5.55 GBq, and the correlation was
positive. The CAT activity was negatively correlated with H2O2 in all observed time points after a
dose o f 3 .70 G Bq, a nd a fter a dose o f 5 .55 G Bq o nly i n 3 0th day following exposure. Results of
multiple linear regression analysis indicated that among all five tested parameters (SOD, CAT, GSH,
O2
.-, H2O2 and .NO), only SOD activity and levels of H2O2 and O2
.- had the statistically significant
importance on TBARS level in blood of DTC patients.
This study showed that treatment with high doses of 131I inducesd an increase in oxidative stress,
seen as increased level of TBARS, disturbed balance of enzymatic and nonenzymatic antioxidant
components and production of free radicals. Understanding of these early redox processes is
important since their progress could affect the latter effects of 131I therapy.
Факултет:
Универзитет у Крагујевцу, Факултет медицинских наукаДатум одбране:
14-12-2018Пројекти:
- Примена биомедицинског инжењеринга у претклиничкој и клиничкој пракси (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41007)
- Фармаколошка анализа ефеката биолошки активних супстанци на изоловане глатке мишиће гастроинтестиналног и урогениталног тракта човека (RS-MESTD-Basic Research (BR or ON)-175007)