Evaluation of the possibility to use calcium channel blockers for prevention of intra-abdominal adhesions formation

Abstract

Aim. To study the possibility of the use of known medications used in cardiology - calcium channel blockers - derivatives of phenylalkilamine (verapamil), benzodiazepine (diltiazem), dihydropyridine (nifedipine) - for prevention of peritoneal adhesion formation. Methods. The study of the effect of different concentrations of medications on nuclear translocation of NF-κB, proliferative and collagen-synthetic activity of fibroblasts was conducted in the primary culture of rats peritoneal fibroblasts with hemoperitoneum. Aseptic injury of peritoneum was caused by modeling of autohemoperitoneum according to original method. Results. It was found that verapamil and diltiazem normalized nuclear translocation of NF-κB, processes of fibroblasts proliferation and their collagen synthesis by optimizing fibroblast functional activity during adhesion formation induction. Verapamil and diltiazem affected fibroblasts similarly but with different intensity. Verapamil in concentrations 0.05 and 0.1 mg/ml and diltiazem in concentration 0.1 mg/ml suppressed the excessive fibroblast activity by inhibiting their proliferative and collagen-synthetic activity, nuclear translocation of NF-κB. Verapamil demonstrated the most prominent pharmacological effect. Nifedepine did not reveal such effect. At the molecular level inhibiting effect of calcium channel blockers verapamil and diltiazem on the activation of apoptosis blocking nuclear transcription factor NF-κB was demonstrated. Conclusion. Verapamil and diltiazem can be recommended for further detailed experimental and clinical studies focused on widening of biological activity spectrum of known medications and area of their clinical use.