Antioxidative 1,4-Dihydropyridine Derivatives Modulate Oxidative Stress and Growth of Human Osteoblast-Like Cells In Vitro
| Autor: | Franz Tatzber, Imanta Bruvere, Lidija Milkovic, Z. A. Kalme, Neven Zarkovic, Gunars Duburs, Zaiga Ogle, Janis Poikans, Egils Bisenieks, Tea Vuković, Astrida Velena |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Physiology Clinical Biochemistry 4-hydroxynonenal (4-HNE) DHPS Pharmacology medicine.disease_cause reactive oxygen species (ROS) cell viability and proliferation Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 1 4-dihydropyridine(s) (DHPs) oxidative stress antioxidant (AO) antioxidative activity (AOA) glutathione parasitic diseases medicine Molecular Biology Biology 1 4-dihydropyridine(s) (DHPs) Chemistry Cell growth lcsh:RM1-950 Cell Biology Glutathione In vitro 3. Good health 030104 developmental biology lcsh:Therapeutics. Pharmacology Second messenger system Uric acid Signal transduction Oxidative stress |
| Zdroj: | Antioxidants Volume 7 Issue 9 Antioxidants, Vol 7, Iss 9, p 123 (2018) |
| ISSN: | 2076-3921 |
| DOI: | 10.3390/antiox7090123 |
| Popis: | Oxidative stress has been implicated in pathophysiology of different human stress- and age-associated disorders, including osteoporosis for which antioxidants could be considered as therapeutic remedies as was suggested recently. The 1,4-dihydropyridine (DHP) derivatives are known for their pleiotropic activity, with some also acting as antioxidants. To find compounds with potential antioxidative activity, a group of 27 structurally diverse DHPs, as well as one pyridine compound, were studied. A group of 11 DHPs with 10-fold higher antioxidative potential than of uric acid, were further tested in cell model of human osteoblast-like cells. Short-term combined effects of DHPs and 50 µ M H2O2 (1-h each), revealed better antioxidative potential of DHPs if administered before a stressor. Indirect 24-h effect of DHPs was evaluated in cells further exposed to mild oxidative stress conditions induced either by H2O2 or tert-butyl hydroperoxide (both 50 µ M). Cell growth (viability and proliferation), generation of ROS and intracellular glutathione concentration were evaluated. The promotion of cell growth was highly dependent on the concentrations of DHPs used, type of stressor applied and treatment set-up. Thiocarbatone III-1, E2-134-1 III-4, Carbatone II-1, AV-153 IV-1, and Diethone I could be considered as therapeutic agents for osteoporosis although further research is needed to elucidate their bioactivity mechanisms, in particular in respect to signaling pathways involving 4-hydroxynoneal and related second messengers of free radicals. |
| Databáze: | OpenAIRE |
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