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The impact of opioids on the effect of cytostatic agents on the C6 and CCF-STTG1 astrocytoma cell lines
Honc, Ondřej ; Novotný, Jiří (advisor) ; Růžička, Jiří (referee)
Despite its numerous side effects, morphine and the opioids derived from this drug, belong among the only effective options for treatment of pain linked to oncological illness. The effect of opioids on the efficiency of cytostatics in vitro has been the subject of many papers but the results are often contradictory, which could be probably caused by the great variability of experimental models and approaches. Some recent studies indicate that the consequences of activation of opioid signaling in astrocytes display certain differences from other cell types. Glioblastoma multiforme, the tumor derived from astrocytes, belong among those with the worst prognosis, mostly for the frequent resistance to cytostatics. In this thesis we focused on the effect of morphine, methadone and DADLE on the efficiency of cytostatics of temozolomide, doxorubicin and vincristine on the cell lines C6 and CCF-STTG1 derived from glioblastomas. Also, we examined the effect of the above mentioned opioids on the level of oxidative cellular stress and using N-acetylcysteine, a ROS scavenger, we verified the role of oxidative stress in cellular systems activated by the effect of the mentioned opioids on the efficiency of cytostatics. We also assessed opioid receptors and the receptor TLR4 in the examined cell lines. The...
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Opioids and neuroprotection: the role of glial cells
Honc, Ondřej ; Novotný, Jiří (advisor) ; Kováčová, Ľubica (referee)
High energy deamand and insulation via the blood-bain barrier are the main reasons for neuronal sensitivity to oxygen or energy deficiency. Even short or mild periods of hypoxia/ischemia (H/I) could fataly impact the CNS enviroment. The area on the edge of the tissue affected by H/I and adjacent unaffected tissue is called the penumbra. Here, we can observe additional H/I related processes - gliosis allied with sterile inflammation and censecutive apoptosis. Opioid receptors attenuate H/I impact on CNS in both acute and consecutive phases. In acute phases, opioid receptors regulate ion homeostasis and attenuate glutamate toxicity; in consecutive phases, lower gliosis manifestation. Both these actions have significant neuroprotective effects. Ability of opioid receptor to lower sterile inflammation in CNS could be used in a series of neurodegenerative diseases, eg. Alzheimer disease or amyotrophic lateral screlosis. Glial cells participate on ion homeostasis, glutamate uptake, and production of antiinflammatory substances; one can, therefore, assume that a significant part of neuroprotective effects of OR is related to glial cells. The opioid system and its signaling pathways has not been fully elucidated yet. I present global overview of this phenomenon and describe some recent findings regarding...
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