Non-Classical Effects of the cAMP Accumulation Activators In Vivo.

Ostap Brek,Tatyana Nosalskaya,Tatyana Bomko,Boris Farber,Artur Martynov

doi:10.34172/apb.2020.059

Abstract

Purpose: Wound-healing dipyridamole- and papaverine-based aerosols (D1/D2) as activators of the accumulation of cyclic adenosine monophosphate are promising drugs that can accelerate wound healing in wound processes of various origins. Methods: 128 rats were used in the study, including 38 in a pharmacological experiment on a model of stencil wounds and 90 in an experiment that studied the effect of spray on the number of CD34 cells in the blood of rats with chemically induced immunodeficiency. Immunodeficiency was caused by the fivefold administration of cyclophosphamide and prednisone. The expression level of CD34 was determined using flow cytofluorimeter. Results: Dipyridamole- and papaverine-based aerosols of two compositions (with and without ascorbic acid) have pronounced reparative properties, significantly accelerating epithelialization and healing of stencil wounds in rats. In terms of this type of action, they are somewhat superior to dexpanthenol. Dipyridamole- and papaverine-based aerosols have the ability to produce beneficial effect on the entire body’s immune system by stimulating the division of pluripotent CD34 cells. The combined effect of papaverine and dipyridamole on tissues leads to selective stimulation of the division of pluripotent cells in the wound, and contributes to a six-fold acceleration of restoration of the animal’s immune system after induced immunodeficiency. Conclusion: Topical application of D1/D2 aerosol samples on the skin of rats contributed to a statistically significant acceleration of regeneration processes. In terms of the appearance of granulations and epithelialization of wounds, D1/D2 aerosols were superior to dexpanthenol ointment.

Highlights

One of the main problems in the effective treatment of severe complications of type 2 diabetes mellitus is diabetic foot syndrome
The combined effect of papaverine and dipyridamole on tissues leads to selective stimulation of the division of pluripotent cells in the wound, and contributes to a six-fold acceleration of restoration of the animal’s immune system after induced immunodeficiency
As an agent for the treatment of trophic ulcers, we have developed a pharmaceutical composition in the form of an aerosol based on a combination of dipyridamole, papaverine and ascorbic acid

Summary

Introduction

One of the main problems in the effective treatment of severe complications of type 2 diabetes mellitus is diabetic foot syndrome. The loss of sensitivity of the lower limbs at the late stages of diabetic neuropathy leads to a foot injury and the appearance of diabetic ulcers. These ulcers do not heal for a very long time; they become contaminated by bacteria, and in the end, would require surgical intervention.[1] As of today, there is no effective remedy that could heal such trophic wounds. Another study has demonstrated that an excessive amount of cAMP in a wound can stimulate the migration of stem cells to the wound area and their rapid differentiation.[3,4]

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