Oral concentrated grape juice suppresses expression of NF-kappa B, TNF-α and iNOS in experimentally induced colorectal carcinogenesis in Wistar rats.
The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane (AOM) and expression of NF-kB, iNOS and TNF- α.


METHODS
Forty male Wistar rats were divided into 7 groups: G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks before AOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juice without AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NF- kB, TNF- and iNOS was evaluated by qPCR.


RESULTS
The number of ACF was higher in G2, and G4 presented a smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4 compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lower in G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed between TNF- α and NF-kB gene expression (p=0.002). In conclusion, the administration of 2% grape juice before AOM reduced the crypt multiplicity, attenuating carcinogenesis. Lower expression of NF-kB was observed in animals exposed to grape juice for a longer period of time, regardless of concentration.
Oncology Group from Gastroenterology Division, Universidade Federal de Sao Paulo, Sao Paulo, Brazil E-mail : nmforones@unifesp.br.
Vanessa Maria de Lima Pazine
VM
Campanholo
Roseane Mendes
RM
Silva
Tiago Donizetti
TD
Silva
Ricardo Artigiani
RA
Neto
Ana Paula Ribeiro
AP
Paiotti
Daniel Araki
DA
Ribeiro
Nora Manoukian
NM
Forones
D058739:Aberrant Crypt Foci / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000235:genetics*; D008517:Phytotherapy; D010936:Plant Extracts; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D027843:Vitis / Q000737:chemistry*
D002273:Carcinogens; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D001397:Azoxymethane