A Novel Adenosine Precursor 2 ',3 '-Cyclic Adenosine Monophosphate Inhibits Formation of Post-surgical Adhesions

作者：Forman Mervyn B; Gillespie Delbert G; Cheng Dongmei; Jackson Edwin K^*

来源：Digestive Diseases and Sciences, 2014, 59(9): 2118-2125.

DOI：10.1007/s10620-014-3139-x

• Post-surgical adhesions
• Adenosine
• Adenosine prodrug
• 2 ',3 '-Cyclic adenosine monophosphate

Intraperitoneal adenosine reduces abdominal adhesions. However, because of the ultra-short half-life and low solubility of adenosine, optimal efficacy requires multiple dosing.
Here, we compared the ability of potential adenosine prodrugs to inhibit post-surgical abdominal adhesions after a single intraperitoneal dose.
Abdominal adhesions were induced in mice using an electric toothbrush to damage the cecum. Also, 20 mu L 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.
The order of efficacy for attenuating adhesion formation was: 2',3'-cyclic adenosine monophosphate > 3',5'-cyclic adenosine monophosphate a parts per thousand adenosine > 5'-adenosine monophosphate a parts per thousand 3'-adenosine monophosphate a parts per thousand 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.
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.

• 出版日期2014-9