Citrus Flavanones Affect Hepatic Fatty Acid Oxidation in Rats by Acting as Prooxidant Agents

Rodrigo Polimeni Constantin,Adelar Bracht,Emy Luiza Ishii-Iwamoto,Clairce Luzia Salgueiro,Renato Polimeni Constantin,Jorgete Constantin,Gilson Soares do Nascimento,Nair Seiko Yamamoto

doi:10.1155/2013/342973

Rodrigo Polimeni Constantin, Adelar Bracht + Show 6 more

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https://doi.org/10.1155/2013/342973

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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.

Highlights

Citrus flavonoids are found at high concentrations in citrus fruits; the most common classes are flavanones, flavones, and flavonols [1]
We evaluated the effects of citrus flavanones (10–300 μM) on oxygen uptake by mitochondria oxidising the medium-chain fatty acid octanoate and the long-chain fatty acid palmitate
The results demonstrated that the activity of oxidising palmitoyl-CoA, which is dependent on peroxisomal fatty acyl-CoA oxidase activity, was unaffected by citrus flavanones at concentrations of up to 200 μM

Summary

Introduction

Citrus flavonoids are found at high concentrations in citrus fruits; the most common classes are flavanones, flavones, and flavonols [1]. These compounds exhibit a wide range of biological activities and positive health effects on mammalian cells, including antiinflammatory, antiatherogenic, and anticancer effects. Not all studies confirm the antioxidant effects of quercetin, fisetin and other flavonoids, and several report that they have prooxidant capabilities [11,12,13] Both quercetin and fisetin are able to promote NADH oxidation because of interactions with cellular enzymes and their abilities to shift cellular conditions to a more oxidised state [12, 13]. This state is reflected by changes in several parameters of BioMed Research International

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