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 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<.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.
Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan.
Yu-Ting
YT
Cheng
Chi-Hao
CH
Wu
Cheng-Ying
CY
Ho
Gow-Chin
GC
Yen
D000818:Animals; D002392:Catechin / Q000494:pharmacology*; D002460:Cell Line; D051545:Cyclooxygenase 1 / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007660:Ketoprofen / Q000009:adverse effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D020011:Protective Agents; D017382:Reactive Oxygen Species; D002392:Catechin; D007660:Ketoprofen; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D051545:Cyclooxygenase 1; C496513:Ptgs1 protein, rat; D005978:Glutathione