Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8529866 | European Journal of Pharmacology | 2018 | 7 Pages |
Abstract
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 15Â min using a spectrophotometer. Subcutaneously (s.c.) injected LPS (1Â mg/kg) reduced the threshold of VMR after 3Â h. Pretreatment with lovastatin (20Â mg/kg s.c. daily for 3 days) abolished this response by LPS. Repeated WAS (1Â h 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, NG-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.
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Authors
Tsukasa Nozu, Saori Miyagishi, Shima Kumei, Rintaro Nozu, Kaoru Takakusaki, Toshikatsu Okumura,