Disruption of redox homeostasis and carcinogen metabolizing enzymes changes by administration of @entity270 to XXXX .

@entity3276 @entity1447 @entity1 @entity270 @entity5 @entity1110 @entity35
AIMS: A large meta-analysis of randomized clinical trials has seriously questioned chemoprevention based on vitamins including @entity270 (VE), and an increased risk for @entity5 among long-term users was actually seen. However, the mechanism underlying these findings still remain unknown. To clarify the mechanism, in an in vivo model we studied the putative disruption of redox homeostasis and the perturbation of carcinogen metabolizing enzymes determined by VE. MAIN METHODS: Male @entity35 were treated ip with either 100 or 200mg/kg b.w. daily for 7 or 14 consecutive days. Controls received vehicle only. @entity1447 ( @entity1447 ) content, @entity1447 -reductase, @entity1447 -linked monooxygenases, as well as phase-II and the antioxidant enzymes catalase and @entity1110 : @entity3276 reductase were investigated in both liver and kidney. Free radical species in tissue subcellular preparations were measured by electronic paramagnetic resonance (EPR) spectroscopy coupled to a radical probe technique. KEY FINDINGS: No substantial changes of hepatic xenobiotic metabolism enzymes were determined by VE. Conversely, a powerful booster effect of various renal phase-I carcinogen bioactivating enzymes at both dosages and observational times was recorded. While no relevant changes of post-oxidative phase-II reactions were found in the liver, a significant inactivating effect was caused by VE in renal tissues. Antioxidant enzymes were found mainly down regulated by the treatment. In the kidney, a marked free radical over-generation linkd to @entity1447 indiction was observed. SIGNIFICANCE: This study proved that VE acts as a co-carcinogen and pro-oxidant agent. Such epigenetic mechanisms may contribute to explain the harmful outcomes observed in @entity1 .
