title: Citrus flavanones affect hepatic fatty acid oxidation in rats by acting as prooxidant agents.
abstract: Citrus flavonoids have a wide range of biological activities and positive health effects on mammalian cells because of their antioxidant properties. However, they also act as prooxidants and thus may interfere with metabolic pathways. The purpose of this work was to evaluate the effects of three citrus flavanones, hesperidin, hesperetin, and naringenin, on several parameters linked to fatty acid oxidation in mitochondria, peroxisomes, and perfused livers of rats. When exogenous octanoate was used as substrate, hesperetin and naringenin reduced the mitochondrial NADH/NAD⁺ ratio and stimulated the citric acid cycle without significant changes on oxygen uptake or ketogenesis. When fatty acid oxidation from endogenous sources was evaluated, hesperetin and naringenin strongly reduced the mitochondrial NADH/NAD⁺ ratio. They also inhibited both oxygen uptake and ketogenesis and stimulated the citric acid cycle. Hesperidin, on the other hand, had little to no effect on these parameters. These results confirm the hypothesis that citrus flavanones are able to induce a more oxidised state in liver cells, altering parameters related to hepatic fatty acid oxidation. The prooxidant effect is most likely a consequence of the ability of these substances to oxidise NADH upon production of phenoxyl radicals in the presence of peroxidases and hydrogen peroxide.
authors.affiliation: Department of Biochemistry, Laboratory of Liver Metabolism, University of Maringá, 87020900 Maringá, PR, Brazil.
authors.forename: Rodrigo Polimeni
authors.initials: RP
authors.lastname: Constantin
authors.forename: Gilson Soares
authors.initials: GS
authors.lastname: do Nascimento
authors.forename: Renato Polimeni
authors.initials: RP
authors.lastname: Constantin
authors.forename: Clairce Luzia
authors.initials: CL
authors.lastname: Salgueiro
authors.forename: Adelar
authors.initials: A
authors.lastname: Bracht
authors.forename: Emy Luiza
authors.initials: EL
authors.lastname: Ishii-Iwamoto
authors.forename: Nair Seiko
authors.initials: NS
authors.lastname: Yamamoto
authors.forename: Jorgete
authors.initials: J
authors.lastname: Constantin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002957:Citrus / Q000737:chemistry; D044950:Flavanones / Q000008:administration & dosage*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006569:Hesperidin / Q000008:administration & dosage*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D044950:Flavanones; D017382:Reactive Oxygen Species; D006569:Hesperidin; C005273:naringenin; C013015:hesperetin