Induction of Hepatic Antioxidant Enzymes by Phenolic Acids in Rats Is Accompanied by Increased Levels of Multidrug Resistance-Associated Protein 3 mRNA Expression

• Published in: The Journal of nutrition Vol. 136; no. 1; pp. 11 - 15
• Main Authors: Yeh, Chi-Tai, Yen, Gow-Chin
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutritional Sciences 2006
• Subjects: Animals; antioxidant activity; ATP Binding Cassette Transporter, Subfamily B - drug effects; ATP Binding Cassette Transporter, Subfamily B - genetics; ATP-Binding Cassette Transporters - drug effects; ATP-Binding Cassette Transporters - genetics; Biological and medical sciences; catalase; Catalase - metabolism; chemoprevention; Coumaric Acids - pharmacology; enzyme activity; Feeding. Feeding behavior; ferulic acid; Fundamental and applied biological sciences. Psychology; gallic acid; Gallic Acid - pharmacology; gene expression; gentisic acid; glutathione peroxidase; Glutathione Peroxidase - metabolism; human diseases; human nutrition; Intestine, Small - drug effects; Intestine, Small - enzymology; liver; Liver - drug effects; Liver - enzymology; Male; males; messenger RNA; multiple drug resistance; neoplasms; p-coumaric acid; Rats; Rats, Sprague-Dawley; small intestine; superoxide dismutase; Superoxide Dismutase - metabolism; transcription factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Nutrition; Rat; Digestive system; Phenolic acid; Enzyme; Induction; Liver; Rodentia; Antioxidant; Gene expression; Protein; antioxidant gene expression; Target tissue resistance; Vertebrata; Mammalia; Animal; multidrug resistance-associated protein; nuclear factor E2-related factor
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/136.1.11

Phenolic acids are widespread in plant foods; they contain important biological and pharmacological properties, some of which were shown to be effective in preventing cancer. We investigated the modulatory effects of phenolic acids on an antioxidant system in male Sprague-Dawley rats. Rats were orally administrated gentisic acid (GEA), gallic acid (GA), ferulic acid (FA), and p-coumaric acid (p-CA) at a dosage of 100 mg/kg body weight for 14 consecutive days. At this dose, the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were greater after administration of all 4 phenolic acids compared with the control group (P < 0.05). The activities of these enzymes in the small intestine of rats were also significantly greater after GA and p-CA treatment compared with controls. The changes in hepatic CuZnSOD, GPx, and catalase mRNA levels induced by phenolic acids were similar to those noted in the enzyme activities. Oxidized glutathione levels were lower (P < 0.05) in the liver of all phenolic acid-supplemented rats, whereas reduced glutathione was markedly higher than in control rats, especially after administration of GA and p-CA. The liver homogenates obtained from rats that had been administered phenolic acids had higher oxygen radical absorbance capacity than those obtained from control rats. Immunoblot analysis revealed an increased total level of Nrf2, a transcription factor governing the antioxidant response element in phenolic acid-supplemented rats. Phenolic acid-mediated antioxidant enzyme expression was accompanied by upregulation of multidrug resistance-associated protein Mrp3. These experiments show that modulation of phase II antioxidant enzymes and oxidative status in the liver by phenolic acids may play an important role in the protection against adverse effects related to mutagenesis and oxidative damage.