Antioxidative 1,4-dihydropyridine derivatives modulate oxidative stress and growth of human osteoblast-like cells in vitro

Milković, Lidija; Vuković, Tea; Žarković, Neven; Tatzber, F.; Bisenieks, E.; Kalme, Z.; Bruvere, I.; Ogle, Z.; Poikans, J.; Velena, A.; Duburs, G. (2018) Antioxidative 1,4-dihydropyridine derivatives modulate oxidative stress and growth of human osteoblast-like cells in vitro. Antioxidants, 7 (9). ISSN 2076-3921

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Abstract

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 uricacid, were further tested in cell model of human osteoblast-like cells. Short-term combined effects ofDHPs and 50μM 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 H2O2or tert-butyl hydroperoxide (both 50μM). 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. ThiocarbatoneIII-1, E2-134-1III-4, CarbatoneII-1, AV-153IV-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.

Item Type:	Article
Uncontrolled Keywords:	1, 4-dihydropyridine(s) (DHPs) ; oxidative stress ; reactive oxygen species (ROS) ; antioxidant (AO) ; antioxidative activity (AOA) ; glutathione ; cell viability and proliferation ; 4-hydroxynonenal (4-HNE)
Subjects:	NATURAL SCIENCES > Biology
Divisions:	Division of Molecular Medicine
Depositing User:	Lidija Milković
Date Deposited:	12 Jun 2019 10:37
URI:	http://fulir.irb.hr/id/eprint/4543
DOI:	10.3390/antiox7090123

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