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    Öğe
    DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ
    (İzmir Demokrasi Üniversitesi, 2021) Özgen, Zeynep Erdoğmuş
    Yüksek antineoplastik aktiviteleri nedeniyle onkolojide en sık kullanılan antrasiklinler arasında yer alan doksorubisin; göğüs, over, testis, tiroid, akciğer kanserlerinde ve birçok sarkomun tedavisinde klinik uygulaması olan önemli ilaçlardan biridir. Ancak doksorubisinin klinik kullanımını kısıtlayan önemli ve ciddi kardiotoksik yan etkisi vardır. Bu derlemede kardiotoksik etki mekanizmasının araştırılması amaçlandı. Araştırma sonucunda kardiotoksisite oluşumunda; nükleik asit ve protein sentezinin inhibisyonu, vazoaktif aminlerin salınımı, mitokondriyal membran potansiyelinde kayıp ve elektron trasport zincirinin inhibisyonu, adrenerjik fonksiyonlardaki değişiklikler, adenilat siklaz, Na+-K+ ATPaz ve Ca+ ATPaz aktivitelerinin azalması gibi mekanizmalar etkili olsa da oksidatif stres ve apoptozisin asıl etken olduğu görülmüştür. Doksorubisinin oluşturduğu kardiotoksisiteyi azaltmaya yönelik koruyucu maddeler araştırmalarda kullanılmış olsa da bu maddelerin klinikte kullanımları yeterli düzeylere ulaşılabilmiş değildir. Yapılan literatür taraması sonucunda, Doksorubisinin oluşturduğu kardiotoksisiteyi azaltmaya yönelik daha ayrıntılı çalışmaların yapılması gerektiği kanaatine varılmıştır.
  • Küçük Resim
    Öğe
    Investigation of dentists' opinions on pharmacovigilance and reporting of adverse effects
    (Dicle Üniversitesi Tıp Fakültesi, 2021) Özgen, Zeynep Erdoğmuş; Erdoğmuş, Zozan
    Objective: In this study, it was aimed to examine the experience, knowledge, and awareness of dentists about adverse drug effects and pharmacovigilance. Methods: In this cross-sectional and descriptive study, a 15-question questionnaire was applied to 100 dentists who are working at Diyarbakir Oral and Dental Health Hospital to evaluate their knowledge, attitudes and practices about adverse effects and pharmacovigilance. Results: 55 percent of dentists stated that they had never encountered an adverse drug reaction (ADR) in their professional life. Even though 45 percent of them reported that they have rarely seen ADR in their professional life, the total number of declarations has been determined as 7.78% of dentists are aware that declaration is required and this is a professional responsibility (86%). Physicians stated that they had no idea how to report ADRs with their current knowledge (81%) and subject of pharmacovigilance was not well covered in the dental education (55%). 86% of them stated that education on this subject should be taken at undergraduate level (internship, education, clinical assignment) and 58% stated that it should be taken in their working life after graduation. Conclusion: This study showed that the dentists participating in the study had a lack of awareness and knowledge about pharmacovigilance and ADR. It was observed that the rate of ADR reporting among physicians was very low compared to the encounter rate. Inclusion of pharmacovigilance in the educational program and providing pre- and post-graduate training to dentists for declaration practices can contribute positively to public health.
  • Küçük Resim
    Öğe
    Protective effects of necrostatin-1 on doxorubicin-induced cardiotoxicity in rat heart
    (Sage Publications INC., 2022) Özgen, Zeynep Erdoğmuş; Erdinç, Meral; Kelle, İlker; Erdinç, Levent; Nergiz, Yusuf
    Background: Doxorubicin (Dox) is one of the most effective antineoplastic drugs which has severe cardiotoxic effects, limiting its clinical usage. Though the exact mechanism of doxorubicin-induced cardiotoxicity is yet to be elucidated, it is shown that production of reactive oxygen species (ROS) increases oxidative stress and leads to cardiomyocyte apoptosis and necroptosis which is also defined as a programmed cell death. Purpose: In the present study, we investigate the effects of necrostatin-1 (Nec-1)-an inhibitor of receptor interaction proteins 1 (RIP1) and necroptosis-on doxorubicin-induced cardiotoxicity in rats. Research Design: Hearts were isolated and perfused by the Langendorff system in all four groups. Perfusion pressure (PP), left ventricular developed pressure (LVDP) and heart rate per minute (HR), LV (dP/dt) max, and LV (dP/dt) min which shows cardiac contractility and relaxation were recorded. Results: Results showed that PP significantly increased with Dox treatment and significantly decreased with Nec-1 treatment, while HR, LVDP, LV (dP/dt) max, and LV (dP/dt) min values significantly decreased with the Dox-treated group and significantly increased with Nec-1 treatment. Also with Nec-1 treatment, gene expression levels of anti-apoptotic Bcl-2 significantly increased and pro-apoptotic protein Bax, apoptotic marker caspase-3, and Nox-2 significantly decreased compared to the Dox-treated group. In heart tissues, MDA levels were significantly increased with Dox and decreased with Nec-1 treatment. These results were supported by the histological analysis indicated that Nec-1 reduced doxorubicin-induced cellular injury. Conclusions: In conclusion, our data indicate that Nec-1 ameliorates doxorubicin-induced cardiotoxicity by reducing oxidative stress injury and attenuating apoptosis and necroptosis.