title: Procyanidin B2 and a cocoa polyphenolic extract inhibit acrylamide-induced apoptosis in human Caco-2 cells by preventing oxidative stress and activation of JNK pathway.
abstract: Humans are exposed to dietary acrylamide (AA) during their lifetime; it is therefore necessary to investigate the mechanisms associated with AA induced toxic effects. Accumulating evidence indicates that oxidative stress may contribute to AA cytotoxicity, but the link between oxidative stress and AA cytotoxicity in the gastrointestinal tract, the primary organ in contact with dietary AA, has not been described. In this study, we evaluate the alterations of the redox balance induced by AA in Caco-2 intestinal cells as well as the potential protective role of natural antioxidants such as a well-standardized cocoa polyphenolic extract (CPE) and its main polyphenol components epicatechin (EC) and procyanidin B2 (PB2). We found that AA-induced oxidative stress in Caco-2 cells is evidenced by glutathione (GSH) depletion and reactive oxygen species (ROS) overproduction. AA also activated the extracellular-regulated kinases and the c-Jun N-amino terminal kinases (JNKs) leading to an increase in caspase-3 activity and cell death. Studies with appropriate inhibitors confirmed the implication of oxidative stress and JNKs activation in AA-induced apoptosis. Additionally, AA cytotoxicity was counteracted by CPE or PB2 by inhibiting GSH consumption and ROS generation, increasing the levels of gamma-glutamyl cysteine synthase and glutathione-S-transferase and blocking the apoptotic pathways activated by AA. Therefore, AA-induced cytotoxicity and apoptosis are closely related to oxidative stress in Caco-2 cells. Interestingly, natural dietary antioxidant such as PB2 and CPE were able to suppress AA toxicity by improving the redox status of Caco-2 cells and by blocking the apoptotic pathway activated by AA.
authors.affiliation: Department of Metabolism and Nutrition, Instituto del Frío-ICTAN, Consejo Superior de Investigaciones Científicas, José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain.
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Rodríguez-Ramiro
authors.forename: Sonia
authors.initials: S
authors.lastname: Ramos
authors.forename: Laura
authors.initials: L
authors.lastname: Bravo
authors.forename: Luis
authors.initials: L
authors.lastname: Goya
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Martín
mesh_terms: D020106:Acrylamide / Q000009:adverse effects*; D017209:Apoptosis; D044946:Biflavonoids / Q000494:pharmacology*; D002099:Cacao / Q000737:chemistry*; D018938:Caco-2 Cells; D002392:Catechin / Q000494:pharmacology*; D016923:Cell Death; D005419:Flavonoids / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D044946:Biflavonoids; D005419:Flavonoids; D010936:Plant Extracts; D059808:Polyphenols; D044945:Proanthocyanidins; D020106:Acrylamide; C479580:procyanidin B2; D002392:Catechin; D048031:JNK Mitogen-Activated Protein Kinases; D005978:Glutathione