title: Effect of resveratrol analogue, DMU-212, on antioxidant status and apoptosis-related genes in rat model of hepatocarcinogenesis.
abstract: The aim of the study was to examine whether antioxidant properties of 3,4,4',5-tetramethoxystilbene (DMU-212) contribute to its anticarcinogenic activity and whether DMU-212 affects the expression of apoptosis-related genes. Two-stage model of hepatocarcinogenesis was used; male Wistar rats were challenged with N-nitrosodiethylamine (NDEA), 200 mg/kg body weight (b.w.), intraperitoneal, then phenobarbital (PB) in drinking water (0.05%) was administered. Simultaneously, DMU-212 was given per os at a dose 20 or 50 mg/kg b.w. two times a week for 16 weeks. DMU-212 caused a moderate decrease in hepatic thiobarbituric acid reactive substances and protein carbonyls concentration elevated in rats treated with NDEA/PB. The activity of antioxidant enzymes examined reduced by NDEA/PB treatment was not restored in rats coadministered with DMU-212. Effects of DMU-212 on messenger RNA (mRNA) expression of antioxidant enzymes in rats challenged with NDEA/PB were diversified; no changes in their protein expression were noted in any of the groups. The expression of 17,000 genes was analyzed by Affymetrix® Rat Gene 1.1 ST Array; 15 apoptosis-related genes were selected and validated by RT-q PCR. The combined treatment with NDEA/PB and DMU-212 increased the mRNA level of some genes driving mitochondria-mediated apoptosis, whereas the mRNA expression of some anti-apoptotic genes triggering receptor-mediated apoptosis was reduced. The expression of genes encoding caspases-4, -8, -9, and -12 was also increased in rats treated with DMU-212. Although antioxidant effect of DMU-212 in rats challenged with NDEA/PB was moderate, its potential anticarcinogenic properties were demonstrated as evidenced by modulation of apoptosis-related genes.
authors.affiliation: 1 Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: H
authors.initials: H
authors.lastname: Piotrowska
authors.affiliation: 1 Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Kujawska
authors.affiliation: 2 Department of Histology and Embryology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Nowicki
authors.affiliation: 1 Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Petzke
authors.affiliation: 3 Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Ignatowicz
authors.affiliation: 3 Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: V
authors.initials: V
authors.lastname: Krajka-Kuźniak
authors.affiliation: 2 Department of Histology and Embryology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Zawierucha
authors.affiliation: 4 Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Wierzchowski
authors.affiliation: 1 Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Murias
authors.affiliation: 1 Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Jodynis-Liebert
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C482492:3,4,5,4'-tetramethoxystilbene; D000975:Antioxidants; D013267:Stilbenes; D000077185:Resveratrol
keywords: 3; 4; 4′; 5-Tetramethoxystilbene (DMU-212); apoptosis-related genes; hepatocarcinogenesis; oxidative stress