Lidocaine-Induced Cell Growth of Human Gingival Fibroblasts. Role of Na⁺-K⁺-ATPase and PKC Activities

Abstract

Background : Evidences have shown that local anaesthetics are clinically useful compounds that exert a pharmacological effect by blocking nerve impulse propagation and also it is able to provoke proliferation and cell growth. Aims : The aim of this study was to investigate the proliferation and cell growth capacity of lidocaine on human gingival fibroblast cells and the different signal pathways involved in its effect. Method : For this purpose in vitro cultures of human gingival fibroblasts were assayed and the effects of lidocaine on proliferation and cell DNA synthesis, Na + -K + -ATPase and PKC activities and K + efflux were also evaluated. Results : Lidocaine stimulated in a concentration-dependent manner proliferation and cell growth of human gingival cells and the mechanism involve an increment in Na + -K + -ATPase and PKC activities, which led to an increase in K + release. All of these effects were blocked by tetrodotoxin, ouabain and calphostin C. In addition, PMA (activator of PKC) increased per se the DNA synthesis of human gingival fibroblast cells. Conclusions : This work demonstrates that lidocaine increase human gingival fibroblasts DNA synthesis and proliferation through an activation of PKC pathway accompanied by the stimulation of Na + -K + -ATPase activity with an increase in K + efflux. These results contribute to showing another action of lidocaine different to its general use as a drug that relieves odontologic pain or acts as an anti-arrithmogenic agent.