Efeito do tacrolimus (FK506) aplicado em minibombas de infusão osmótica na regeneração do nervo ciático de ratos wistar

Abstract

Introduction : Injuries in peripheral nerves are common in clinical practice being responsible for serious problems and often permanent as loss of motor, sensitive functions, acute and chronic pain. Although surgical, physiotherapy and diagnostic techniques have evolved in recent decades, the clinical outcomes of nerve recovery still unsatisfactory, which encourages many researchers to seek drugs and devices that may help regeneration (NOBLE et al, 1998; OLIVEIRA et al, 2004). Various trophic factors, also known as growth factors (GF) are used and tested in vitro and in vivo in an attempt to assist the regeneration of peripheral nerves. These proteins act directly on the proliferation and differentiation of various cell types, being able to promote tissue repair and functional recovery (BOYD AND GORDON, 2003). Among them, we highlight the FK506 (Tacrolimus), a ligand for immunophilins with strong immunosuppressive effect that has potential neurotrophic and neuroprotective actions. Studies have shown that FK506 increases the rate of axonal regeneration and also the level of necessary reinnervation after peripheral nerve injury, besides enhancing recovery from nerve damage. Objective : Evaluating in vivo the availability and effect of FK 506 on the repair of injury of rat sciatic nerve. Material and Methods : Thirty-six male adult Wistar rats were randomized into three groups (I - control, II - Systemic FK506 III - FK506 site;). To evaluate the effect of different treatments, the sciatic nerve of animals was transected, creating a defect of 10 mm and then tubulized with the silicone chamber. In the control group, no additional treatment was performed. In systemic group, FK506 (dose 0.1 mg/kg/day) was administered systemically via osmotic minipump ALZET while in the local group the administration also occurred through the ALZET osmotic minipump, but adapted to release into the silicone chamber the same dose. The performed treatment lasted 90 days. Results : Data from the present study suggest that the immunosuppressive drug FK506 has a positive effect on the nervous functional improvement and the use of osmotic minipumps is effective in continuous dispensing of the drug. The most important finding of this research is that the degree of functional recovery, measured by the rate of sciatic function after injury with loss of substance and repair through tubing, it is better when FK506 is administered locally whether compared to systemic administration in animal models. No other studies have used local application of the drug with constant release rate for comparison were found.