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A neurokinin‐1 receptor antagonist (NK‐1RA) that reduces postoperative adhesions inhibits leukocyte recruitment and increases antioxidant capacity in the peritoneal cavity
Author(s) -
Reed Karen L,
Heydrick Stanley J,
Prushik Scott G,
Gower Adam C,
Stucchi Arthur F,
Leeman Susan E,
Becker James M
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a817-b
Subject(s) - myeloperoxidase , oxidative stress , reactive oxygen species , pharmacology , respiratory burst , peritoneal fluid , chemistry , adhesion , peritoneal cavity , antioxidant , nadph oxidase , immunology , medicine , inflammation , surgery , biochemistry , organic chemistry
Substance P (SP), a NK‐1R ligand, facilitates leukocyte recruitment and reactive oxygen species (ROS) generation. We have shown in rats that intraperitoneal administration of a NK‐1RA within 6 hrs of surgery reduces adhesion formation at 7 days and decreases peritoneal ROS at 24 hrs. To gain a better understanding of the actions of SP and the NK‐1R immediately after surgery we determined the effects of NK‐1RA administration on peritoneal leukocyte recruitment and oxidative stress within 6 hrs of surgery. Methods: Adhesions were surgically induced in rats receiving NK‐1RA (CJ‐12,255, Pfizer) or vehicle. Peritoneal tissue and fluid were collected at 2, 4, and 6 hrs and analyzed for myeloperoxidase (MPO), a neutrophil marker, and for NADPH oxidase (NOX) and 8‐isoprostanes (8‐IP), indicators of oxidative stress. The antioxidant capacity of peritoneal fluid was determined. Levels were compared to those in non‐operated animals. Results: Adhesion formation was associated with increased NOX, 8‐IP and MPO levels at 6 hrs compared to non‐op (P<0.05). The NK‐1RA blocked the increase in MPO, reduced 8‐IP and did not affect NOX. The antioxidant capacity of peritoneal fluid was elevated (P<0.05) in NK‐1RA administered animals at all time points. Conclusion: SP activation of the NK‐1R directly after surgery may promote adhesion formation, in part, by increasing neutrophil recruitment and oxidative stress in the peritoneum.