Mechanism Data

Mechanistic Studies of EvitarTM 

Presented at Society of Reproductive Investigations, San Diego, March 9th, 2018

Evitar™ Regulates Key Signaling Molecules in the Pathogenesis of Postoperative Tissue Fibrosis...click here

Lynne M. Robertson1, M.S., PhD, Nicole M. Fletcher, PhD2, Michael P. Diamond, MD3, Ghassan M. Saed, PhD4

1 Temple Therapeutics B.V., Geleen, The Netherlands, 2 & 4 Wayne State University, Detroit, MI, USA, 3 Endicronologist and Fertility Obstetrician & Gynecologist, Augusta, GA, USA

Background

Hypoxia and the resultant oxidative stress play an important role in the development, incidence and severity of post-operative adhesions.

The inflammatory response to injury, such as hypoxia sustained during surgical procedures, involves a complex cascade of events orchestrated, at least in part, by hypoxia inducible factor (HIF)-1α.  

Among the key events in the cascade are induction of transforming growth factor-b1 (TGF-β1) cellular and vascular endothelial growth factor (VEGF), and development of the adhesion phenotype in peritoneal fibroblasts, all of which promote the profibrotic inflammatory response.  Fibrin and collagen deposition at the wound site, as part of the healing process, helps to establish a foundation for peritoneal wound healing.  When such processes proceed unchecked, as in the fibrotic state, peritoneal adhesion formation results.

L-Alanyl-L-Glutamine (Ala-Gln) is a dipeptide comprised of two amino acids, alanine and conditionally essential glutamine. Glutamine’s known biological effects suggest a potential role for Ala-Gln in preventing postsurgical adhesions by modulating early events in wound healing and the cellular response to hypoxia.

 

Objectives

To determine the effect of EvitarTM (L-Alanyl-L-Glutamine) on HIF-1α and type I collagen levels in normal human peritoneal fibroblasts under conditions of continuous or episodic hypoxia, compared to prehypoxic or untreated controls.

 

Conclusions

EvitarTM significantly and persistently suppressed hypoxia-induced levels of key adhesion phenotype markers, HIF1α and type 1 collagen, under conditions of continuous as well as episodic hypoxia in normal peritoneal fibroblasts, in vitro

EvitarTM suppression of hypoxic induction of HIF-1α, a known trigger of the inflammatory response that culminates in fibrosis, suggests potential therapeutic value for the dipeptide in the prevention of postoperative adhesions. 

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