title: Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A.
abstract: Diosmetin (DIOS) is a flavone aglycone commonly occurring in citrus species and olive leaves, in addition it is one of the active ingredients of some medications. Based on both in vitro and in vivo studies several beneficial effects are attributed to DIOS but the biochemical background of its action seems to be complex and it has not been completely explored yet. Previous investigations suggest that most of the flavonoid aglycones have negative effect on ATP synthesis in a dose dependent manner. In our study 17 flavonoids were tested and interestingly DIOS caused a significant elevation of intracellular ATP levels after 6- and 12-h incubation in MDCK kidney cells. In order to understand the mechanism of action, intracellular ATP and protein levels, ATP/ADP ratio, cell viability and ROS levels were determined after DIOS treatment. In addition, impacts of different enzyme inhibitors and effect of DIOS on isolated rat liver mitochondria were also tested. Finally, the influence of DIOS on the ATP depleting effect of the mycotoxin, ochratoxin A was also investigated. Our major conclusions are the followings: DIOS increases intracellular ATP levels both in kidney and in liver cells. Inhibition of glycolysis or citric acid cycle does not decrease the observed effect. DIOS-induced elevation of ATP levels is completely abolished by the inhibition of ATP synthase. DIOS is able to completely reverse the ATP-depleting effect of the mycotoxin, ochratoxin A. Most probably the DIOS-induced impact on ATP system does not originate from the antioxidant property of DIOS. Based on our findings DIOS may be promising agent to positively influence ATP depletion caused by some metabolic poisons.
authors.affiliation: Institute of Laboratory Medicine, University of Pécs, Pécs H-7624, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Poór
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs H-7624, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Veres
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs H-7624, Hungary.
authors.forename: Péter B
authors.initials: PB
authors.lastname: Jakus
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs H-7624, Hungary.
authors.forename: Csenge
authors.initials: C
authors.lastname: Antus
authors.affiliation: Institute of Laboratory Medicine, University of Pécs, Pécs H-7624, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Montskó
authors.affiliation: Institute of Laboratory Medicine, University of Pécs, Pécs H-7624, Hungary.
authors.forename: Zita
authors.initials: Z
authors.lastname: Zrínyi
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb, Croatia.
authors.forename: Sanda
authors.initials: S
authors.lastname: Vladimir-Knežević
authors.affiliation: Department of Medical Biochemistry and Haematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb, Croatia.
authors.forename: József
authors.initials: J
authors.lastname: Petrik
authors.affiliation: Institute of Laboratory Medicine, University of Pécs, Pécs H-7624, Hungary. Electronic address: koszegit@freemail.hu.
authors.forename: Tamás
authors.initials: T
authors.lastname: Kőszegi
mesh_terms: D025181:ATP Synthetase Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009793:Ochratoxins / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005419:Flavonoids; D009793:Ochratoxins; D017382:Reactive Oxygen Species; C025589:ochratoxin A; D000255:Adenosine Triphosphate; D025181:ATP Synthetase Complexes; C039602:diosmetin
keywords: ATP; Diosmetin; Flavonoids; Kidney cells; Ochratoxin A