title: Concentrated grape juice (G8000™) reduces immunoexpression of iNOS, TNF-alpha, COX-2 and DNA damage on 2,4,6-trinitrobenzene sulfonic acid-induced-colitis.
abstract: Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. Flavonoids exert several biological activities, which are mainly related to their ability to inhibit inflammatory process and/or to their antioxidant properties, and are able to regulate the immune response. The aim of this study was to evaluate whether phenolic compounds present in grape juice could reduce the inflammatory effects induced by experimental colitis. A total of 41 male Wistar rats were randomized into seven groups, as follows: G1--Sham group: sham induced-colitis rats; G2--(2,4,6-rinitrobenzenesulfonic acid) TNBS group: nontreated induced-colitis; G3--2% grape juice control group; G4--1% grape juice 24h after TNBS colitis induction; G5--1% grape juice on day 7 after colitis induction; G6--2% grape juice 24h after colitis induction; G7--2% grape juice on day 7 after colitis induction. Genotoxicity was evaluated by comet assay. Immunohistochemistry was determined using the streptavidin-biotin-peroxidase method being analyzed in control (normal tissue) and "hot spot" areas i.e., presenting inflammatory process being graded as 1 (weak), 2 (moderate), or 3 (strong). Both parameters were evaluated in the cytoplasm of epithelial or inflammatory cells. TNF-immunoexpression and iNOS were reduced after drinking grape juice 24 h or after 7 days for all doses tested. COX-2 was reduced in the groups exposed to 1% grape juice 24 h or 7 days of exposure. The grape juice at 1% dose in the last 7 days of treatment as well as grape juice at 2% dose decreased the peripheral blood genotoxicity. Taken together, the grape juice mainly at 1% dose exerts anti-inflammatory effects in chronic colitis caused by TNBS as a result of down regulation in the expression of pro-inflammatory cytokines and reduction of genotoxicity in peripheral blood cells.
authors.affiliation: Department of Pathology, Universidade Federal de São Paulo - Escola Paulista de Medicina, UNIFESP, SP, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Marchi
authors.affiliation: Department of Pathology, Universidade Federal de São Paulo - Escola Paulista de Medicina, UNIFESP, SP, Brazil.
authors.forename: Ana Paula Ribeiro
authors.initials: AP
authors.lastname: Paiotti
authors.affiliation: Department of Pathology, Universidade Federal de São Paulo - Escola Paulista de Medicina, UNIFESP, SP, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Artigiani Neto
authors.affiliation: Department of Pathology, Universidade Federal de São Paulo - Escola Paulista de Medicina, UNIFESP, SP, Brazil.
authors.forename: Celina Tizuko Fujiyama
authors.initials: CT
authors.lastname: Oshima
authors.affiliation: Department of Pathology, Universidade Federal de São Paulo - Escola Paulista de Medicina, UNIFESP, SP, Brazil; Department of Biosciences, Universidade Federal de São Paulo, UNIFESP, Santos, SP, Brazil. Electronic address: daribeiro@unifesp.br.
authors.forename: Daniel Araki
authors.initials: DA
authors.lastname: Ribeiro
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001628:Beverages; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D020552:Comet Assay; D051546:Cyclooxygenase 2 / Q000276:immunology; D004249:DNA Damage / Q000187:drug effects; D005638:Fruit; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D027843:Vitis
chemical_list: D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat
keywords: Grape juice; Inflammatory bowel disease; TNBS-colitis