Zinc L-carnosine protects colonic mucosal injury through induction of heat shock protein 72 and suppression of NF-kappaB activation.
In this study, we investigated the effects of zinc L-carnosine, an anti-ulcer drug, on acetic acid-induced colonic mucosal injury and the correlation of these effects with expression of 72-kDa heat shock proteins (HSP72) and nuclear factor kappa B (NF-kappaB) activation in rat colonic mucosa in vivo. After intrarectal administration of zinc L-carnosine, the rats received intrarectal infusion of 5% acetic acid (1 ml). The colonic mucosal damage was evaluated by macroscopic assessments 24 h after the intrarectal infusion of acetic acid. Expression of HSP72 in rat colonic mucosa was evaluated by Western blot analysis before and after zinc L-carnosine administration. NF-kappaB activation was evaluated by electrophoretic mobility shift assays (EMSA). Zinc L-carnosine inhibited visible damage in rat colonic mucosa by acetic acid. Expression of HSP72 was significantly increased at 6 h after zinc L-carnosine administration. Furthermore, NF-kappaB activation in colonic mucosa was suppressed 6 h after zinc L-carnosine treatment. These results suggested that zinc L-carnosine protects the colonic mucosa against acetic acid by induction of HSP72 and suppression of NF-kappaB activation and zinc L-carnosine may be a novel therapeutic agent for the therapy of inflammatory bowel disease.
Odashima
Masaru
M
Department of Gastroenterology, Akita University School of Medicine, 1-1-1, Hondo, Akita City, Akita 010-8543, Japan. odashima@doc.med.akita-u.ac.jp
Otaka
Michiro
M
Jin
Mario
M
Wada
Isao
I
Horikawa
Youhei
Y
Matsuhashi
Tamotsu
T
Ohba
Reina
R
Hatakeyama
Natsumi
N
Oyake
Jinko
J
Watanabe
Sumio
S
D019342:Acetic Acid; D000285:Administration, Rectal; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D050884:HSP72 Heat-Shock Proteins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D050884:HSP72 Heat-Shock Proteins; D016328:NF-kappa B; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D002336:Carnosine; D015032:Zinc; D019342:Acetic Acid