doctoralThesis
Efeito neuroprotetor do óleo essencial da Lippia alba sobre a neuropatia causada por constrição do nervo ciático de ratos
Fecha
2021-03-05Registro en:
SOUZA, Daniele Oliveira. Efeito neuroprotetor do óleo essencial da Lippia alba sobre a neuropatia causada por constrição do nervo ciático de ratos. 2021. 104f. Tese (Doutorado em Psicobiologia) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2021.
Autor
Souza, Daniele Oliveira
Resumen
Peripheral nerve injuries are a public health problem. Motor, sensory, autonomic deficits and the
development of Neuropathic Pain (NP), resulting from peripheral nerve injuries, can compromise
patients' quality of life. After nerve damage, oxidative stress occurs and the release of
inflammatory cytokines and allogeneic mediators that induce NP. The occurrence of these
problems instigates the search in nature for compounds for the manipulation of new drugs.
Lippia alba is a medicinal plant whose essential oil has biological activity in the Peripheral
Nervous System (SNP). The aim of this study is to evaluate the effect of treatment with Lippia
alba essential oil (OELa) on peripheral neuropathy caused by Chronic Sciatic Nerve Constriction
(CCNC) in rats. Thirty Rattus novergicus (Wistar) rats, of both sexes, with body mass varying
between 200-250 g were used. The animals were divided into the experimental groups: Control
treated vehicle (CON), control treated with OELa 100 mg / Kg, v.o. (CON + OELa), group
submitted to CCNC treated with vehicle solution (CCNC) and group submitted to CCNC treated
with OELa 100 mg / Kg (CCNC + OELa). Oral treatment was administered 30 minutes before
the CCNC was performed on the animal's right sciatic nerve and for 14 consecutive days. The
pain hypersensitivity test was performed, using the von Frey test and hot plate, 24 hours before
CCNC induction (day 0), and on days 5, 7, 9 and 14 after CCNC. On the 14th day after CCNC,
the animals were euthanized. Afterwards, dissection of the right and left sciatic nerve was
performed to analyze the extracellular recording of the Compound Action Potential (PAC). The
evaluated parameters of the PAC were: Pico-a-Pico Amplitude (APP), chronaxia, reobase,
positive amplitude, conduction speed and duration of the 1st and 2nd components of the PAC.
The phytochemical analysis of OELa identified a quantitative variation of substances, the major
compound of which was citral (geranial with 42.59% and neral with 28.21%). The evaluation of
the mechanical sensitivity presented in the CON an average of 20.87 g for the threshold of
reaction to the stimulus. In the CCNC group, there was an increase in applied force of 72.4%,
thus increasing the threshold for removing the paw on the 5th day after CCNC. However, on
days 7, 9 and 14, there was a significant increase in the reaction to the stimulus with less force
applied, decreasing by 54.65%, 59.34% and 58.8% on days 7, 9 and 14, respectively, in relation
to the CON group, characterizing mechanical hyperalgesia. The CCNC + OELa group increased
the threshold to the mechanical stimulus by 116.79%, 145.4%, 54.56% and 62% on the
evaluation days 5, 7, 9 and 14, respectively in relation to the CON. In the CON + OELa group it
also showed an increase of 141.2% from the 5th evaluation, showing greater response on the 7th
evaluation day, presenting an increase of 260%. There was no significant difference in the
sensitivity of the thermal stimulus in rats submitted to CCNC and CON group. However, in the
CON+OELa group there was an increase of 56.25% in the stimulus threshold on the 7th day of
evaluation, compared to the CON. In the other experimental groups, there was no significant
difference. CCNC caused electrophysiological changes in all evaluated parameters. The sciatic
nerve excitability in the CCNC group increased by 27.53%, by reducing the reobase, compared
to the CON. Meanwhile, the chronaxia value increased by 54.89% in the CCNC group in relation
to the CON. In the CCNC+OELa group, the rheobase increased by 39.5%, compared to the
CCNC group, the chronaxia in this group did not change. The reobase in the CON + OELa group
differed by 16.5% in relation to the CON. And APP decreased by 54.8% compared to CON. The
positive amplitude of the first component in the CCNC group decreased by 52.53% in relation to
the CON. In the CCNC + OELa group, it decreased 74.59%. The CON+OELa group also
showed a 57% reduction. The second component was not registered in the CCNC group.
However, this was preserved when CCNC was associated with treatment with OELa (CCNC +
OELa), presenting a decrease in amplitude of 88.14% in relation to the CON. The CON + OELa
group also decreased the amplitude of the second component by 34.78% in relation to the CON.
As for the speed of conduction of the PAC, the CCNC group showed a 44.73% reduction in the first component of the PAC, compared to the CON. Treatment with OELa (CCNC + OELa)
reversed this decrease by 102.96%, compared to the CCNC group. The other experimental
groups showed no statistical difference. In the second component of the PAC, the conduction
velocity was not altered in the CCNC+OELa and CON+OELa groups compared to the CON.
The duration of the first component of the CAP increased by 45.21% in the group submitted to
CCNC, compared to the CON. The other groups showed no significant difference compared to
the CON. As for the duration of the second component of the PAC, in the CCNC group it was
not possible to evaluate, due to an unregistered visa. In the other experimental groups, there was
no statistical difference in relation to the CON. The results showed that treatment with OELa in
animals submitted to CCNC, decreased the hypersensitivity of peripheral neuropathy and also
showed a potential neuroprotective effect when preserving fibers that constitute the action
potential of the compound. Evidence of the behavioral and electrophysiological data of the PAC,
suggesting an anesthetic effect of the OELa. Therefore, the neuroprotective action of OELa in
reducing neuronal damage caused by CCNC, contributes to the preservation of the structure and
function of the myelinated sheath and axons. The mechanisms by which OELa has a potential
neuroprotective effect against peripheral nerve damage have yet to be elucidated. However, our
results represent evidence that oral supplementation with OELa promotes a decrease in
hypersensitivity after neuronal injury that points to a combination of multiple targets, involving
neuronal and immunological components, which triggers effects on the modulation of
neuropathic sensitivity.