Novel approach to reduce postsurgical adhesions to a minimum: administration of losartan plus atorvastatin intraperitoneally

J Surg Res. 2013 May 1;181(1):91-8. doi: 10.1016/j.jss.2012.05.035. Epub 2012 May 31.

Abstract

Background: Intraperitoneal adhesions are the most important cause of intestinal obstruction, pelvic pain, and female infertility.

Materials and methods: Losartan (1, 5, and 10 mg/kg), atorvastatin (1, 20, and 30 mg/kg), losartan (10 mg/kg) plus atorvastatin (20 mg/kg), and sodium hyaluronate/carboxymethylcellulose (HA/CMC) were administered intraperitoneally in 90 male NMRI mice. After 7 d, the grade of adhesions was scored by two scaling methods and the concentrations of TGF-β1, tPA, and PAI-1 were also evaluated.

Results: Simultaneous intraperitoneal administration of losartan and atorvastatin led to a much higher reduction of adhesions compared with that in the HA/CMC group (P < 0.05). When losartan plus atorvastatin was administered, significant changes in the serum concentration and mRNA expression, including the increase of tPA and the decrease of TGF-β1 and PAI-1, were observed compared with those in other groups.

Conclusions: Our findings suggest that the simultaneous application of losartan and atorvastatin leads to an enhanced reduction in adhesion bands more than that of HA/CMC treatment, compared with the control group, possibly through balancing the expression of TGF-β1, tPA, and PAI-1.

MeSH terms

  • Angiotensin Receptor Antagonists / administration & dosage*
  • Animals
  • Atorvastatin
  • Heptanoic Acids / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Injections, Intraperitoneal
  • Losartan / administration & dosage*
  • Male
  • Mice
  • Plasminogen Activator Inhibitor 1 / blood
  • Plasminogen Activator Inhibitor 1 / genetics
  • Postoperative Complications / prevention & control*
  • Pyrroles / administration & dosage*
  • RNA, Messenger / analysis
  • Tissue Adhesions / prevention & control*
  • Tissue Plasminogen Activator / blood
  • Transforming Growth Factor beta1 / blood
  • Transforming Growth Factor beta1 / genetics

Substances

  • Angiotensin Receptor Antagonists
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Plasminogen Activator Inhibitor 1
  • Pyrroles
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Atorvastatin
  • Tissue Plasminogen Activator
  • Losartan