Letters in Drug Design & Discovery

Author(s): Atena Soleimani, Fereshteh Asgharzadeh, Nikoo Saeedi, Amir Avan, Mikhail Ryzhikov, Majid Khazaei and Seyed Mahdi Hasanian Mehr*

DOI: 10.2174/0115701808323064241210055454

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Role of a Dual Inhibitor of RAS/PI3K/AKT and RAS/RAF/MEK on Post-surgical Adhesion Band Formation
  • * (Excluding Mailing and Handling)

Abstract

Introduction: This study evaluated the effects of Rigosertib (RGS) on the prevention of intra-abdominal adhesions in a mouse model.

Methods: Eighteen mice were divided into three groups: Sham (no abrasion or adhesion), Positive Control (surgical abrasion and adhesion), and Rigosertib Treatment (200 mg/kg/day intraperitoneally for 7 days). Adhesions were induced through cecal abrasion and assessed using Nair and Leach adhesion scoring systems. Histological evaluations were performed using Haematoxylin & Eosin (H & E) and Masson's trichrome stains in order to analyze inflammatory cell infiltration and collagen deposition.

Results: Results showed that RGS administration did not have a significant impact on the formation or rigidity of adhesion bands compared to the positive control group. Both Nair and Leach scoring systems confirmed the lack of significant differences. Histological analysis revealed no reduction in inflammatory responses or collagen deposition in RGS-treated mice. H & E staining showed similar inflammatory cell infiltration across all groups, while Masson's trichrome staining indicated no differences in fibrosis levels between treated and untreated mice. In conclusion, Rigosertib did not demonstrate efficacy in down-regulating peritoneal adhesions or associated inflammatory responses and fibrosis in this mouse model.

Conclusion: These findings suggest that Rigosertib may not be suitable for preventing intraabdominal adhesions, warranting further investigation into alternative therapeutic strategies.

Keywords: Rigosertib, RAS signaling, post-surgical adhesion band formation, Inflammation, Fibrosis, Intra-abdominal adhesions.