Conotoxin MVIIA improves cell viability and antioxidant system after spinal cord injury in rats.
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2018
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Abstract
This study evaluates whether intrathecal MVIIA injection after spinal cord injury (SCI) elicits
neuroprotective effects. The test rats were randomly distributed into six groups— sham, placebo, MVIIA 2.5 μM, MVIIA 5 μM, MVIIA 10 μM, and MVIIA 20 μM—and were administered
the treatment four hours after SCI. After the optimal MVIIA dose (MVIIA 10 μM) was defined,
the best time for application, one or four hours, was analyzed. Locomotor hind limb function
and side effects were assessed. Forty-eight hours after the injury and immediately after
euthanasia, spinal cord segments were removed from the test rats. Cell viability, reactive
oxygen species, lipid peroxidation, and glutamate release were investigated. To examine
the MVIIA mechanism of action, the gene expressions of pro-apoptotic (Bax, nNOS, and
caspase-3, -8, -9, -12) and anti-apoptotic (Bcl-xl) factors in the spinal cord tissue samples
were determined by real-time PCR, and the activities of antioxidant enzymes were also
investigated. Application of intrathecal MVIIA 10 μM four hours after SCI prompted a neuroprotective effect: neuronal death decreased (22.46%), oxidative stress diminished, pro-apoptotic factors (Bax, nNOS, and caspase-3, -8) were expressed to a lesser extent, and
mitochondrial viability as well as anti-apoptotic factor (Bcl-xl) expression increased. These
results suggested that MVIIA provided neuroprotection through antioxidant effects. Indeed,
superoxide dismutase (188.41%), and glutathione peroxidase (199.96%), reductase
(193.86%), and transferase (175.93%) expressions increased. Therefore, intrathecal
MVIIA (MVIIA 10 μM, 4 h) application has neuroprotective potential, and the possible mechanisms are related to antioxidant agent modulation and to intrinsic and extrinsic apoptotic
pathways.
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OLIVEIRA, K. M. de et al. Conotoxin MVIIA improves cell viability and antioxidant system after spinal cord injury in rats. PLoS One, v. 13, n. 10, p. 1-26, out. 2018. Disponível em: <https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204948>. Acesso em: 25 fev. 2019.