Liver and colon DNA oxidative damage and gene expression profiles of rats fed Arabidopsis thaliana mutant seeds containing contrasted flavonoids.
Plant polyphenols, such as flavonoids, comprise many compounds, ranging from simple phenolic molecules (i.e. flavonols, anthocyanins) to polymeric structures with high molecular weight (as proanthocyanidins, PAs). We investigated the effects of flavonoids by feeding Wistar rats Arabidopsis thaliana seeds carrying mutations in key enzymes of the flavonoid biosynthetic pathway (15% w/w seeds for 4 weeks). The seeds used were: Ws-2 wild-type containing flavonols and PAs, tt3-4 mutant containing flavonols only, ban-5 accumulating flavonols and anthocyanins, tt4-8 mutant, deprived of flavonoids. DNA oxidative damage was significantly reduced only in the liver of rats fed tt3-4 mutant seeds. Microarray analysis of the liver revealed down-regulation of genes associated with oxidative stress, Krebs cycle, electron transport and proteasome degradation in all experimental groups compared to the tt4-8-fed reference rats; therefore, these effects were due to the flavonol content and not to high molecular weight compounds. We observed a down-regulation of inflammatory response genes in the colon mucosa in ban-5- fed rats, probably due to anthocyanin content. In conclusion, flavonols exhibited antioxidant effects at systemic level, whereas high molecular weight flavonoids affected only the colon, probably due to their limited absorption.
Luceri
Cristina
C
Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. cristina.luceri@unifi.it <cristina.luceri@unifi.it>
Giovannelli
Lisa
L
Pitozzi
Vanessa
V
Toti
Simona
S
Castagnini
Cinzia
C
Routaboul
Jean-Marc
JM
Lepiniec
Loic
L
Larrosa
Mar
M
Dolara
Piero
P
D000818:Animals; D017360:Arabidopsis / Q000235:genetics*; D016000:Cluster Analysis; D003106:Colon / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage / Q000502:physiology*; D004032:Diet; D005419:Flavonoids / Q000235:genetics* / Q000633:toxicity*; D020869:Gene Expression Profiling; D005838:Genotype; D017403:In Situ Hybridization; D008099:Liver / Q000187:drug effects*; D008297:Male; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects; D030821:Plants, Genetically Modified; D011786:Quality Control; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012639:Seeds / Q000737:chemistry
D005419:Flavonoids; D012313:RNA