Activation of oxidative stress response by hydroxyl substituted chalcones and cyclic chalcone analogues in mitochondria.
We investigated the effect of hydroxyl substituted chalcone (1a) and some chalcone analogues (1b-d) on isolated rat liver mitochondria to gain new insights into the cytotoxic mechanism of these compounds. We observed an inhibitory effect on phosphorylation and the partial uncoupling of compounds 1a and 1d. Increased radical generation and possible covalent interaction of the compounds with cellular thiols resulted in glutathione (GSH) depletion and modulation of the investigated mitochondrial activities. Disruption of interconnected mechanisms as electron transport chain and energetic metabolism, ROS production and insufficiency of antioxidant defensive system could lead to induction of cell death.
Guzy
J
J
Department of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, P J Safárik University, Kosice, Slovak Republic.
Vasková-Kubálková
J
J
Rozmer
Z
Z
Fodor
K
K
Mareková
M
M
Poskrobová
M
M
Perjési
P
P
D000818:Animals; D047188:Chalcones / Q000737:chemistry* / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D047188:Chalcones; D005978:Glutathione