Induction of hepatic antioxidant enzymes by phenolic acids in rats is accompanied by increased levels of multidrug resistance-associated protein 3 mRNA expression

Chi Tai Yeh, Gow Chin Yen

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140 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)11-15
Number of pages5
JournalJournal of Nutrition
Volume136
Issue number1
Publication statusPublished - Jan 2006
Externally publishedYes

Fingerprint

multiple drug resistance
phenolic acids
Antioxidants
antioxidants
Messenger RNA
liver
Liver
rats
Enzymes
enzymes
Gallic Acid
proteins
p-coumaric acid
gallic acid
ferulic acid
Glutathione Peroxidase
glutathione peroxidase
Catalase
glutathione
catalase

Keywords

  • Antioxidant gene expression
  • Multidrug resistance-associated protein
  • Nuclear factor E2-related factor
  • Phenolic acid

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

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title = "Induction of hepatic antioxidant enzymes by phenolic acids in rats is accompanied by increased levels of multidrug resistance-associated protein 3 mRNA expression",
abstract = "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.",
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N2 - 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.

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