PMID- 17202747
OWN - NLM
STAT- MEDLINE
DCOM- 20070312
LR  - 20190911
IS  - 1347-8613 (Print)
IS  - 1347-8613 (Linking)
VI  - 103
IP  - 1
DP  - 2007 Jan
TI  - Tacrolimus (FK506), an immunosuppressive agent, prevents indomethacin-induced 
      small intestinal ulceration in the rat: inhibition of inducible nitric oxide 
      synthase expression.
PG  - 40-7
AB  - We examined the effect of tacrolimus (FK506), an immunosuppressive drug, on 
      indomethacin-induced small intestinal ulceration in rats. Animals were given 
      indomethacin (10 mg/kg, s.c.), killed 24 h later, and myeloperoxidase (MPO) 
      activity and thiobarbituric acid reactants (TBARS) were evaluated in intestinal 
      lesions. Tacrolimus (0.3 - 3 mg/kg) was administered p.o. twice 0.5 h before and 
      6 h after indomethacin injection. The expression of inducible nitric oxide 
      synthase (iNOS) mRNA was determined by a TaqMan real-time RT-PCR, while the 
      activity of nuclear factor (NF)-kappaB DNA-binding was analyzed by 
      electrophoresis mobility shift assays (EMSA) 6 h after indomethacin treatment. 
      Indomethacin provoked severe hemorrhagic lesions in the small intestine, mainly 
      in the jejunum and ileum, accompanied with increases in MPO activity and TBARS. 
      Oral administration of tacrolimus reduced the severity of indomethacin-induced 
      intestinal lesions in a dose-dependent manner. The increases in MPO activity and 
      TBARS were also significantly attenuated by tacrolimus. The expression of iNOS 
      mRNA was markedly enhanced when examined 6 h after indomethacin administration, 
      and this response was counteracted by tacrolimus. Indomethacin also activated 
      NF-kappaB in a tacrolimus-preventable manner. These results suggest that 
      tacrolimus prevents indomethacin-induced small intestinal ulceration in the rat. 
      This effect may be due to inhibition of iNOS induction through suppression of 
      NF-kappaB activation.
FAU - Kato, Shinichi
AU  - Kato S
AD  - Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical 
      University, Misasagi, Yamashina, Kyoto 607-8414, Japan. skato@mb.kyoto-phu.ac.jp
FAU - Nishio, Hikaru
AU  - Nishio H
FAU - Ogura, Michitaka
AU  - Ogura M
FAU - Takeuchi, Koji
AU  - Takeuchi K
LA  - eng
PT  - Journal Article
DEP - 20070101
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - WM0HAQ4WNM (Tacrolimus)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Animals
MH  - Immunosuppressive Agents/*pharmacology
MH  - Indomethacin/*antagonists & inhibitors
MH  - Intestinal Diseases/chemically induced/*prevention & control
MH  - Lipid Peroxidation/drug effects
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide Synthase Type II/*antagonists & inhibitors/genetics
MH  - Peroxidase/metabolism
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tacrolimus/*pharmacology
MH  - Tumor Necrosis Factor-alpha/genetics
MH  - Ulcer/chemically induced/*prevention & control
EDAT- 2007/01/05 09:00
MHDA- 2007/03/14 09:00
CRDT- 2007/01/05 09:00
PHST- 2007/01/05 09:00 [pubmed]
PHST- 2007/03/14 09:00 [medline]
PHST- 2007/01/05 09:00 [entrez]
AID - JST.JSTAGE/jphs/FP0061181 [pii]
AID - 10.1254/jphs.fp0061181 [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2007 Jan;103(1):40-7. doi: 10.1254/jphs.fp0061181. Epub 2007 Jan 
      1.