A novel adenosine precursor 2',3'-cyclic adenosine monophosphate inhibits formation of post-surgical adhesions.
BACKGROUND
Intraperitoneal adenosine reduces abdominal adhesions. However, because of the ultra-short half-life and low solubility of adenosine, optimal efficacy requires multiple dosing.


OBJECTIVE
Here, we compared the ability of potential adenosine prodrugs to inhibit post-surgical abdominal adhesions after a single intraperitoneal dose.


METHODS
Abdominal adhesions were induced in mice using an electric toothbrush to damage the cecum. Also, 20 μL of 95 % ethanol was applied to the cecum to cause chemically induced injury. After injury, mice received intraperitoneally either saline (n = 18) or near-solubility limit of adenosine (23 mmol/L; n = 12); 5'-adenosine monophosphate (75 mmol/L; n = 11); 3'-adenosine monophosphate (75 mmol/L; n = 12); 2'-adenosine monophosphate (75 mmol/L; n = 12); 3',5'-cyclic adenosine monophosphate (75 mmol/L; n = 19); or 2',3'-cyclic adenosine monophosphate (75 mmol/L; n = 20). After 2 weeks, adhesion formation was scored by an observer blinded to the treatments. In a second study, intraperitoneal adenosine levels were measured using tandem mass spectrometry for 3 h after instillation of 2',3'-cyclic adenosine monophosphate (75 mmol/L) into the abdomen.


RESULTS
The order of efficacy for attenuating adhesion formation was: 2',3'-cyclic adenosine monophosphate > 3',5'-cyclic adenosine monophosphate ≈ adenosine > 5'-adenosine monophosphate ≈ 3'-adenosine monophosphate ≈ 2'-adenosine monophosphate. The groups were compared using a one-factor analysis of variance, and the overall p value for differences between groups was p < 0.000001. Intraperitoneal administration of 2',3'-cAMP yielded pharmacologically relevant levels of adenosine in the abdominal cavity for >3 h.


CONCLUSIONS
Administration of 2',3'-cyclic adenosine monophosphate into the surgical field is a unique, convenient and effective method of preventing post-surgical adhesions by acting as an adenosine prodrug.
St. Joseph Translational Research Institute, St. Joseph Hospital of Atlanta, Atlanta, GA, USA, formanm@bellsouth.net.
Mervyn B
MB
Forman
Delbert G
DG
Gillespie
Dongmei
D
Cheng
Edwin K
EK
Jackson
D000227:Adenine Nucleotides / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000241:Adenosine / Q000493:pharmacokinetics / Q000627:therapeutic use; D000249:Adenosine Monophosphate / Q000493:pharmacokinetics / Q000627:therapeutic use; D000282:Administration, Intravaginal; D000818:Animals; D000242:Cyclic AMP / Q000493:pharmacokinetics / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D011183:Postoperative Complications / Q000517:prevention & control*; D013997:Time Factors; D000267:Tissue Adhesions / Q000517:prevention & control*
D000227:Adenine Nucleotides; D000249:Adenosine Monophosphate; C010565:2',3'-cyclic AMP; D000242:Cyclic AMP; D000241:Adenosine