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Akutna strupenost izbranih tirozin kinaznih inhibitorjev ocenjena na eksperimentalnem modelu zarodkov cebric
Leben, Karin (Author), Eleršek, Tina (Mentor) More about this mentor... This link opens in a new window

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Abstract
Zaradi vse večje rabe farmacevtikov naraščajo njihove koncentracije v okolju, kar predstavlja tveganje za okolje. Skupina farmacevtikov z izrednim razcvetom v zadnjih nekaj letih so tudi protirakava zdravila. Zaradi razširjenosti in pogostosti bolezni – raka – se je veliko vlagalo v razvoj novih zdravil in tehnik, pri čemer so velik napredek doživeli tirozin kinazni inhibitorji (TKI). Ti spadajo med tarčna zdravila, saj neposredno inhibirajo določene tirozinske kinaze tumorja. V naši raziskavi smo želeli oceniti toksičen vpliv sorafeniba, nilotiniba in regorafeniba na eksperimentalnem modelu zarodkov rib cebric (Danio rerio). Posamezne zarodke smo za 96 ur izpostavili izbranim koncentracijam omenjenih inhibitorjev ter dnevno beležili njihov razvoj. Prav tako smo določili letalne, sub-letalne in teratogene učinke. Ugotovili smo, da sorafenib in nilotinib ne povečata deleža letalnih, sub-letalnih ali teratogenih učinkov pri zarodkih vse do najvišje testirane koncentracije. Regorafenib ni povzročil letalnih učinkov, značilno pa se je povečal delež sub-letalnih in teratogenih znakov po 48 urah pri koncentraciji 1,9 mg/L, po 96 urah pa pri koncentraciji od 0,6 mg/L dalje. Sorafenib in regorafenib sta prav tako po 96 urah značilno znižala delež izvaljenih zarodkov, in sicer sorafenib pri koncentraciji 1,8 mg/L in regorafenib pri 0,6 mg/L in 1,9 mg/L. Glede na razmerje predvidene okoljske koncentracije in koncentracije, ki ne povzroča učinkov, nobeden od testiranih TKI ne predstavlja tveganja za okolje. Potrebno je tudi poudariti, da je naša raziskava omenjenih TKI prva v Sloveniji.

Language:Slovenian
Keywords:ekotoksičnost, tirozin kinazni inhibitorji, cebrice, sorafenib, nilotinib, regorafenib
Work type:Master's thesis/paper (mb22)
Organization:BF - Biotechnical Faculty
Year:2020
COBISS.SI-ID:22395651 This link opens in a new window
Views:280
Downloads:120
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Secondary language

Language:English
Title:Acute toxicity of selected tyrosine kinase inhibitors assessed in the experimental model of zebrafish embryo
Abstract:
With the increasing use of pharmaceuticals, their concentrations in the environment are increasing, posing a risk to the environment. A group of pharmaceuticals, with a remarkable boom in the last few years, are also anti-cancer drugs. Due to the prevalence and frequency of the disease – cancer – a lot has been invested in the development of new drugs and techniques, where great progress has been made with tyrosine kinase inhibitors (TKIs). They're classified as targeted drugs because they act directly on certain tumor tyrosine kinases that they inhibit. In our study, we wanted to evaluate the toxic effect of sorafenib, nilotinib, and regorafenib on an experimental model of the zebrafish embryo (Danio rerio). Individual embryos were exposed to selected concentrations of these inhibitors for 96 hours, and their development was recorded daily. We also determined lethal, sub-lethal and teratogenic effects. We found that sorafenib and nilotinib didn't increase lethal, sub-lethal or teratogenic effects in embryos up to the highest tested concentration. Regorafenib didn't cause lethal effects, but it significantly increased the sub-lethal and teratogenic characters after 48 hours at a concentration of 1,9 mg/L and after 96 hours at a concentration of 0,6 mg/L onwards. Sorafenib and regorafenib also significantly reduced the hatching rate of embryos after 96 hours, namely sorafenib at 1,8 mg/L and regorafenib at 0,6 mg/L and 1,9 mg/L. According to the ratio of predicted environmental concentration and predicted no effect concentration, none of the tested TKIs present an environmental risk. It should also be emphasized that our research is the first in Slovenia for these TKIs.

Keywords:ecotoxicity, tyrosine kinase inhibitors, zebrafish, sorafenib, nilotinib, regorafenib

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