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Catechin protects against ketoprofen-induced oxidative damage of the gastric mucosa by up-regulating Nrf2 in vitro and in vivo

Nonsteroidal anti-inflammatory drugs (NSAIDs), including ketoprofen, are widely used in clinical medicine. However, these drugs may damage the gastrointestinal mucosa. Some reports have suggested that intestinal diseases, such as ulcers, are associated with lipid peroxidation and oxidative damage in...

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Published in:The Journal of nutritional biochemistry 2013-02, Vol.24 (2), p.475-483
Main Authors: Cheng, Yu-Ting, Wu, Chi-Hao, Ho, Cheng-Ying, Yen, Gow-Chin
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description Nonsteroidal anti-inflammatory drugs (NSAIDs), including ketoprofen, are widely used in clinical medicine. However, these drugs may damage the gastrointestinal mucosa. Some reports have suggested that intestinal diseases, such as ulcers, are associated with lipid peroxidation and oxidative damage in the mucosa. Phytochemicals, such as polyphenols, are common dietary antioxidants that possess many beneficial characteristics, such as antioxidant and anti-inflammatory capabilities. The objective of this study was to investigate the protective effects of polyphenols on ketoprofen-induced oxidative damage in the gastrointestinal mucosa. We evaluated the effects of catechin, theaflavin, malvidin, cyanidin and apigenin on the activity of antioxidant enzymes in human intestinal-407 (Int-407) cells and rat primary gastric cells treated with ketoprofen. The results indicated that catechin significantly (P
doi_str_mv 10.1016/j.jnutbio.2012.01.010
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However, these drugs may damage the gastrointestinal mucosa. Some reports have suggested that intestinal diseases, such as ulcers, are associated with lipid peroxidation and oxidative damage in the mucosa. Phytochemicals, such as polyphenols, are common dietary antioxidants that possess many beneficial characteristics, such as antioxidant and anti-inflammatory capabilities. The objective of this study was to investigate the protective effects of polyphenols on ketoprofen-induced oxidative damage in the gastrointestinal mucosa. We evaluated the effects of catechin, theaflavin, malvidin, cyanidin and apigenin on the activity of antioxidant enzymes in human intestinal-407 (Int-407) cells and rat primary gastric cells treated with ketoprofen. The results indicated that catechin significantly (P&lt;.05) decreased the levels of lipid peroxidation (40.5%) and reactive oxygen species (30.0%), and increased the activity of intracellular antioxidant enzymes glutathione peroxidase, glutathione reductase and total sulfhydryl groups. More importantly, the treatment of Sprague–Dawley rats with catechin (35 mg/kg/day) prior to the administration of ketoprofen (50 mg/kg/day) successfully inhibited oxidative damage and reversed the impairment of the antioxidant system in the intestinal mucosa. Western blot analysis revealed that catechin stimulated a time-dependent increase in both the nuclear factor erythroid 2-related factor 2 and total heme oxygenase-1 protein expression in Int-407 cells. These results suggest that catechin may have a protective effect on gastrointestinal ulcers.</description><identifier>ISSN: 0955-2863</identifier><identifier>EISSN: 1873-4847</identifier><identifier>DOI: 10.1016/j.jnutbio.2012.01.010</identifier><identifier>PMID: 22704780</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; antioxidant activity ; Antioxidant enzymes ; antioxidants ; apigenin ; Catechin ; Catechin - pharmacology ; Cell Line ; Cyclooxygenase 1 - genetics ; digestive system diseases ; DNA Damage - drug effects ; gastric mucosa ; Gastric Mucosa - drug effects ; Gastric Mucosa - metabolism ; Gastric Mucosa - pathology ; Gastric ulcer ; Glutathione - metabolism ; glutathione peroxidase ; Glutathione Peroxidase - metabolism ; glutathione-disulfide reductase ; heme oxygenase (decyclizing) ; Heme Oxygenase-1 - metabolism ; HO-1 ; Humans ; intestinal mucosa ; Intestinal Mucosa - drug effects ; Intestinal Mucosa - metabolism ; Intestinal Mucosa - pathology ; Ketoprofen ; Ketoprofen - adverse effects ; L-Lactate Dehydrogenase - metabolism ; lipid peroxidation ; Lipid Peroxidation - drug effects ; Male ; malvidin ; medicine ; Membrane Proteins - genetics ; NF-E2-Related Factor 2 - metabolism ; Nrf2 ; NSAID ; Oxidative Stress - drug effects ; phytochemicals ; Protective Agents - pharmacology ; protective effect ; protein synthesis ; Rats ; Rats, Sprague-Dawley ; reactive oxygen species ; Reactive Oxygen Species - metabolism ; sulfhydryl groups ; Up-Regulation ; Western blotting</subject><ispartof>The Journal of nutritional biochemistry, 2013-02, Vol.24 (2), p.475-483</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. 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However, these drugs may damage the gastrointestinal mucosa. Some reports have suggested that intestinal diseases, such as ulcers, are associated with lipid peroxidation and oxidative damage in the mucosa. Phytochemicals, such as polyphenols, are common dietary antioxidants that possess many beneficial characteristics, such as antioxidant and anti-inflammatory capabilities. The objective of this study was to investigate the protective effects of polyphenols on ketoprofen-induced oxidative damage in the gastrointestinal mucosa. We evaluated the effects of catechin, theaflavin, malvidin, cyanidin and apigenin on the activity of antioxidant enzymes in human intestinal-407 (Int-407) cells and rat primary gastric cells treated with ketoprofen. The results indicated that catechin significantly (P&lt;.05) decreased the levels of lipid peroxidation (40.5%) and reactive oxygen species (30.0%), and increased the activity of intracellular antioxidant enzymes glutathione peroxidase, glutathione reductase and total sulfhydryl groups. More importantly, the treatment of Sprague–Dawley rats with catechin (35 mg/kg/day) prior to the administration of ketoprofen (50 mg/kg/day) successfully inhibited oxidative damage and reversed the impairment of the antioxidant system in the intestinal mucosa. Western blot analysis revealed that catechin stimulated a time-dependent increase in both the nuclear factor erythroid 2-related factor 2 and total heme oxygenase-1 protein expression in Int-407 cells. These results suggest that catechin may have a protective effect on gastrointestinal ulcers.</description><subject>Animals</subject><subject>antioxidant activity</subject><subject>Antioxidant enzymes</subject><subject>antioxidants</subject><subject>apigenin</subject><subject>Catechin</subject><subject>Catechin - pharmacology</subject><subject>Cell Line</subject><subject>Cyclooxygenase 1 - genetics</subject><subject>digestive system diseases</subject><subject>DNA Damage - drug effects</subject><subject>gastric mucosa</subject><subject>Gastric Mucosa - drug effects</subject><subject>Gastric Mucosa - metabolism</subject><subject>Gastric Mucosa - pathology</subject><subject>Gastric ulcer</subject><subject>Glutathione - metabolism</subject><subject>glutathione peroxidase</subject><subject>Glutathione Peroxidase - metabolism</subject><subject>glutathione-disulfide reductase</subject><subject>heme oxygenase (decyclizing)</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>HO-1</subject><subject>Humans</subject><subject>intestinal mucosa</subject><subject>Intestinal Mucosa - drug effects</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestinal Mucosa - pathology</subject><subject>Ketoprofen</subject><subject>Ketoprofen - adverse effects</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>lipid peroxidation</subject><subject>Lipid Peroxidation - drug effects</subject><subject>Male</subject><subject>malvidin</subject><subject>medicine</subject><subject>Membrane Proteins - genetics</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Nrf2</subject><subject>NSAID</subject><subject>Oxidative Stress - drug effects</subject><subject>phytochemicals</subject><subject>Protective Agents - pharmacology</subject><subject>protective effect</subject><subject>protein synthesis</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>sulfhydryl groups</subject><subject>Up-Regulation</subject><subject>Western blotting</subject><issn>0955-2863</issn><issn>1873-4847</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqFkU2PFCEQhonRuOPqT1A5eukRaGi6T8ZM_Eo2etA9Ez6KXsbpZgR64l787TLp0aMmlUCRp6qo90XoOSVbSmj3er_dz0sxIW4ZoWxLaA3yAG1oL9uG91w-RBsyCNGwvmuv0JOc94QQxkX3GF0xJgmXPdmgXztdwN6FGR9TrLeSsR51mHPB36HE-uhhbsLsFgsOx5_B6RJOgJ2e9Ag4elzuAI86lxQsnhYbs8bmHi_HJsG4HCo9j_hz8gzXGadQUsR6dmtyik_RI68PGZ5dzmt0-_7dt93H5ubLh0-7tzeN5XIoDfPEG9OCaM2gnZe8FcZ540VHB2Il474FJoShg5TWcAoDUKFZb10nhBasvUav1r51oR8L5KKmkC0cDnqGuGRFWc8E5bIbKipW1KaYcwKvjilMOt0rStRZerVXF-nVWXpFaA1S615cRixmAve36o_WFXi5Al5HpccUsrr9Wjvw6ktdiNJ_EkwweSberARUsU4Bkso2wFy9Camap1wM__nmbyyXrAo</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Cheng, Yu-Ting</creator><creator>Wu, Chi-Hao</creator><creator>Ho, Cheng-Ying</creator><creator>Yen, Gow-Chin</creator><general>Elsevier Inc</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130201</creationdate><title>Catechin protects against ketoprofen-induced oxidative damage of the gastric mucosa by up-regulating Nrf2 in vitro and in vivo</title><author>Cheng, Yu-Ting ; Wu, Chi-Hao ; Ho, Cheng-Ying ; Yen, Gow-Chin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-2f0fbb3e53b9adf7435bdfbf56190c724f3e255b1977cb41e9e15a28cd655a523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>antioxidant activity</topic><topic>Antioxidant enzymes</topic><topic>antioxidants</topic><topic>apigenin</topic><topic>Catechin</topic><topic>Catechin - pharmacology</topic><topic>Cell Line</topic><topic>Cyclooxygenase 1 - genetics</topic><topic>digestive system diseases</topic><topic>DNA Damage - drug effects</topic><topic>gastric mucosa</topic><topic>Gastric Mucosa - drug effects</topic><topic>Gastric Mucosa - metabolism</topic><topic>Gastric Mucosa - pathology</topic><topic>Gastric ulcer</topic><topic>Glutathione - metabolism</topic><topic>glutathione peroxidase</topic><topic>Glutathione Peroxidase - metabolism</topic><topic>glutathione-disulfide reductase</topic><topic>heme oxygenase (decyclizing)</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>HO-1</topic><topic>Humans</topic><topic>intestinal mucosa</topic><topic>Intestinal Mucosa - drug effects</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestinal Mucosa - pathology</topic><topic>Ketoprofen</topic><topic>Ketoprofen - adverse effects</topic><topic>L-Lactate Dehydrogenase - metabolism</topic><topic>lipid peroxidation</topic><topic>Lipid Peroxidation - drug effects</topic><topic>Male</topic><topic>malvidin</topic><topic>medicine</topic><topic>Membrane Proteins - genetics</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Nrf2</topic><topic>NSAID</topic><topic>Oxidative Stress - drug effects</topic><topic>phytochemicals</topic><topic>Protective Agents - pharmacology</topic><topic>protective effect</topic><topic>protein synthesis</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>sulfhydryl groups</topic><topic>Up-Regulation</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Yu-Ting</creatorcontrib><creatorcontrib>Wu, Chi-Hao</creatorcontrib><creatorcontrib>Ho, Cheng-Ying</creatorcontrib><creatorcontrib>Yen, Gow-Chin</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of nutritional biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Yu-Ting</au><au>Wu, Chi-Hao</au><au>Ho, Cheng-Ying</au><au>Yen, Gow-Chin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Catechin protects against ketoprofen-induced oxidative damage of the gastric mucosa by up-regulating Nrf2 in vitro and in vivo</atitle><jtitle>The Journal of nutritional biochemistry</jtitle><addtitle>J Nutr Biochem</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>24</volume><issue>2</issue><spage>475</spage><epage>483</epage><pages>475-483</pages><issn>0955-2863</issn><eissn>1873-4847</eissn><abstract>Nonsteroidal anti-inflammatory drugs (NSAIDs), including ketoprofen, are widely used in clinical medicine. 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The results indicated that catechin significantly (P&lt;.05) decreased the levels of lipid peroxidation (40.5%) and reactive oxygen species (30.0%), and increased the activity of intracellular antioxidant enzymes glutathione peroxidase, glutathione reductase and total sulfhydryl groups. More importantly, the treatment of Sprague–Dawley rats with catechin (35 mg/kg/day) prior to the administration of ketoprofen (50 mg/kg/day) successfully inhibited oxidative damage and reversed the impairment of the antioxidant system in the intestinal mucosa. Western blot analysis revealed that catechin stimulated a time-dependent increase in both the nuclear factor erythroid 2-related factor 2 and total heme oxygenase-1 protein expression in Int-407 cells. These results suggest that catechin may have a protective effect on gastrointestinal ulcers.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22704780</pmid><doi>10.1016/j.jnutbio.2012.01.010</doi><tpages>9</tpages></addata></record>
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subjects Animals
antioxidant activity
Antioxidant enzymes
antioxidants
apigenin
Catechin
Catechin - pharmacology
Cell Line
Cyclooxygenase 1 - genetics
digestive system diseases
DNA Damage - drug effects
gastric mucosa
Gastric Mucosa - drug effects
Gastric Mucosa - metabolism
Gastric Mucosa - pathology
Gastric ulcer
Glutathione - metabolism
glutathione peroxidase
Glutathione Peroxidase - metabolism
glutathione-disulfide reductase
heme oxygenase (decyclizing)
Heme Oxygenase-1 - metabolism
HO-1
Humans
intestinal mucosa
Intestinal Mucosa - drug effects
Intestinal Mucosa - metabolism
Intestinal Mucosa - pathology
Ketoprofen
Ketoprofen - adverse effects
L-Lactate Dehydrogenase - metabolism
lipid peroxidation
Lipid Peroxidation - drug effects
Male
malvidin
medicine
Membrane Proteins - genetics
NF-E2-Related Factor 2 - metabolism
Nrf2
NSAID
Oxidative Stress - drug effects
phytochemicals
Protective Agents - pharmacology
protective effect
protein synthesis
Rats
Rats, Sprague-Dawley
reactive oxygen species
Reactive Oxygen Species - metabolism
sulfhydryl groups
Up-Regulation
Western blotting
title Catechin protects against ketoprofen-induced oxidative damage of the gastric mucosa by up-regulating Nrf2 in vitro and in vivo
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