Essential Oil of Croton zehntneri Prevents Conduction Alterations Produced by Diabetes Mellitus on Vagus Nerve

Abstract

Autonomic diabetic neuropathy (ADN) is a complication of diabetes mellitus (DM), to which there is no specific treatment. In this study, the efficacy of the essential oil of Croton zehntneri (EOCz) in preventing ADN was evaluated in the rat vagus nerve. For the two fastest conducting myelinated types of axons of the vagus nerve, the conduction velocities and rheobase decreased, whilst the duration of the components of the compound action potential of these fibers increased. EOCz completely prevented these DM-induced alterations of the vagus nerve. Unmyelinated fibers were not affected. In conclusion, this investigation demonstrated that EOCz is a potential therapeutic agent for the treatment of ADN.

Keywords: Croton zehntneri; autonomic diabetic neuropathy; compound action potential; essential oil; vagus nerve.

Figure 1

Characterization of the experimental model of diabetes mellitus induced by streptozotocin in adult rats. Panel (A) shows post-prandial blood glucose concentration; panel (B) shows body mass; panel (C) shows water intake; and panel (D) shows food consumption. Same legend for all panels. CT, control; DB, diabetic; and DB + EOCz, diabetic treated with EOCz groups. The data are expressed as mean ± E.PM and * p < 0.05 compared to all isochronous respective values of the CT group, one-way ANOVA followed by the Dunn’s or Holm–Sidak method. There were no statistical differences between groups DB and DB + EOCz.

Figure 2

Characterization of extracellular recording of the compound action potential (CAP). Representative traces of the CAP of myelinated (A,B) and unmyelinated fibers (C,D). The upper traces illustrate the effect of removing Na⁺ from the extracellular solution, while the lower traces illustrate the effect of lidocaine (1 mM) on the CAP of vagal fibers. The 1st, 2nd, and 3rd indicate the CAP components for both registers.

Figure 3

Representative traces of the compound action potential (CAP) of the vagus nerve. The left and right columns show the CAP traces of the myelinated or unmyelinated fibers, respectively, for control (CT, panel A or D), diabetic (DB, panel B or E), and diabetic animals treated with EOCz (DB + EOCz, panel C or F). The asterisks indicate the stimulus artifacts.

Figure 4

Preventive effect of EOCz treatment on the alterations produced by DM on the conductibility of myelinated and unmyelinated fibers of the vagus nerve. Panels (A–C) represent peak-to-peak amplitude, conduction velocity and half width duration, respectively, of CAP myelinated fibers, whilst panels (D–F) represent, respectively, the same above parameters for unmyelinated fibers. The 1st, 2nd, and 3rd indicated at the bottom of each graph refer to the components (waves) viewed on the myelinated and unmyelinated CAP. Same legend for all panels: CT, control; DB, diabetic; DB + EOCz, diabetic treated with EOCz. Data are presented as mean ± E.P.M and *, p < 0.05, when compared to control and to DB + EOCz groups (one-way ANOVA, followed by Dunn’s method).

Figure 5

Effect of EOCz treatment on DM-induced alterations of excitability of myelinated and unmyelinated vagal fibers. Rheobase and chronaxie are shown on panels (A,B), respectively, for myelinated, and on panels (C,D) for unmyelinated fibers. CT, control; DB, diabetic; DB + EOCz, diabetic treated with EOCz. Data are presented as mean ± E.P.M and * p < 0.05, when compared to control (one-way ANOVA, followed by the Holm–Sidak method).