PMID- 29107672
OWN - NLM
STAT- MEDLINE
DCOM- 20180806
LR  - 20180806
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 818
DP  - 2018 Jan 5
TI  - Lovastatin inhibits visceral allodynia and increased colonic permeability induced 
      by lipopolysaccharide or repeated water avoidance stress in rats.
PG  - 228-234
LID - S0014-2999(17)30722-7 [pii]
LID - 10.1016/j.ejphar.2017.10.056 [doi]
AB  - Statins have been reported to block inflammatory somatic pain and have an 
      anti-cytokine property. Lipopolysaccharide (LPS) or repeated water avoidance 
      stress (WAS) induces visceral hypersensitivity and increases gut permeability in 
      rats, which are mediated through proinflammatory cytokine-dependent pathways. 
      Since visceral hypersensitivity with increased gut permeability plays a crucial 
      role in the pathophysiology of irritable bowel syndrome (IBS), these above animal 
      models are considered to simulate IBS. We hypothesized that lovastatin improves 
      symptoms in the patients with IBS by attenuating these visceral changes. The 
      threshold of visceromotor response (VMR) induced by colonic balloon distention 
      was measured for the assessment of visceral sensation in rats. Colonic 
      permeability was determined in vivo by quantifying the absorbed Evans blue in 
      colonic tissue for 15min using a spectrophotometer. Subcutaneously (s.c.) 
      injected LPS (1mg/kg) reduced the threshold of VMR after 3h. Pretreatment with 
      lovastatin (20mg/kg s.c. daily for 3 days) abolished this response by LPS. 
      Repeated WAS (1h daily for 3 days) induced visceral allodynia, which was also 
      blocked by repeated injection of lovastatin before each stress session. The 
      antinociceptive effect of lovastatin on the LPS-induced allodynia was reversed by 
      mevalonolactone, N(G)-nitro-L-arginine methyl ester or naloxone. Lovastatin also 
      blocked the LPS- or repeated WAS-induced increased gut permeability. These 
      results indicate the possibility that lovastatin can be useful for treating IBS.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Nozu, Tsukasa
AU  - Nozu T
AD  - Department of Regional Medicine and Education, Asahikawa Medical University, 
      2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan. Electronic 
      address: tnozu@sea.plala.or.jp.
FAU - Miyagishi, Saori
AU  - Miyagishi S
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 
      078-8510, Japan. Electronic address: miyagishi@asahikawa-med.ac.jp.
FAU - Kumei, Shima
AU  - Kumei S
AD  - Department of General Medicine, Asahikawa Medical University, 2-1-1-1 
      Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan. Electronic address: 
      kumei@asahikawa-med.ac.jp.
FAU - Nozu, Rintaro
AU  - Nozu R
AD  - Department of Regional Medicine and Education, Asahikawa Medical University, 
      2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan. Electronic 
      address: rintaro.1500@gmail.com.
FAU - Takakusaki, Kaoru
AU  - Takakusaki K
AD  - Research Center for Brain Function and Medical Engineering, Asahikawa Medical 
      University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan. 
      Electronic address: kusaki@asahikawa-med.ac.jp.
FAU - Okumura, Toshikatsu
AU  - Okumura T
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 
      078-8510, Japan; Department of General Medicine, Asahikawa Medical University, 
      2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan. Electronic 
      address: okumurat@asahikawa-med.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20171028
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Analgesics)
RN  - 0 (Lipopolysaccharides)
RN  - 059QF0KO0R (Water)
RN  - 9LHU78OQFD (Lovastatin)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Analgesics/pharmacology/therapeutic use
MH  - Animals
MH  - *Avoidance Learning
MH  - Colon/*drug effects/*metabolism
MH  - Hyperalgesia/*drug therapy/metabolism/psychology
MH  - Lipopolysaccharides/*pharmacology
MH  - Lovastatin/*pharmacology/therapeutic use
MH  - Male
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Permeability/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Stress, Psychological
MH  - Water
OTO - NOTNLM
OT  - Gut permeability
OT  - Irritable bowel syndrome
OT  - Lipopolysaccharide
OT  - Lovastatin
OT  - Visceral pain
OT  - Water avoidance stress
EDAT- 2017/11/07 06:00
MHDA- 2018/08/07 06:00
CRDT- 2017/11/07 06:00
PHST- 2017/09/26 00:00 [received]
PHST- 2017/10/26 00:00 [revised]
PHST- 2017/10/27 00:00 [accepted]
PHST- 2017/11/07 06:00 [pubmed]
PHST- 2018/08/07 06:00 [medline]
PHST- 2017/11/07 06:00 [entrez]
AID - S0014-2999(17)30722-7 [pii]
AID - 10.1016/j.ejphar.2017.10.056 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2018 Jan 5;818:228-234. doi: 10.1016/j.ejphar.2017.10.056. Epub 
      2017 Oct 28.