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Published on: December 17, 2014
Systemic effects induced by intralesional injection of ω-conotoxin MVIIC after spinal cord injury in rats
Karen M Oliveira1, Carla Maria O Silva1, Mário Sérgio L Lavor2
1Departamento de Clínica e Cirurgia Veterinária, Escola de Veterinária, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG CEP 30123-970, Brasil.
Background:
Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes.
Results:
The clinical, hematologic and biochemical evaluation revealed no significant abnormalities in all groups, even in high doses. There was no significant alteration in organs, except for degenerative changes in kidneys at a dose of 120 pmol.
Conclusions:
These findings suggest that MVIIC at 15, 30 and 60 pmol are safe for intralesional administration after spinal cord injury and could be further investigated in relation to its neuroprotective effects. However, 120 pmol doses of MVIIC may provoke adverse effects on kidney tissue.
Insights
Marine conotoxin MVIIC shows promise for spinal cord injury treatment. Doses of 15-60 pmol were safe in rats, but 120 pmol caused kidney damage, indicating potential toxicity.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Calcium channel blockers, including conotoxins, show potential in reducing brain and spinal cord injury.
- Marine conotoxin MVIIC (α-conotoxin MVIIC) has demonstrated neuroprotective effects in in vitro models of ischemia.
- Previous studies indicated potential clinical side effects of MVIIC, necessitating investigation into its systemic effects and organ toxicity.
Purpose of the Study:
- To investigate the potential toxic effects of MVIIC on various organs.
- To evaluate the clinical and blood profiles of rats following spinal cord injury and MVIIC treatment.
Main Methods:
- Rats with spinal cord injury were treated intralesionally with placebo or MVIIC at doses of 15, 30, 60, or 120 pmol.
- Histopathological examination of kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine was performed seven days post-administration.
- Blood samples were analyzed for hematologic and biochemical changes.
Main Results:
- No significant clinical, hematologic, or biochemical abnormalities were observed across all MVIIC dose groups.
- Histopathological analysis revealed no significant organ alterations, except for degenerative changes in the kidneys at the highest dose (120 pmol).
Conclusions:
- MVIIC doses of 15, 30, and 60 pmol are considered safe for intralesional administration post-spinal cord injury.
- These lower doses warrant further investigation for their neuroprotective potential.
- A dose of 120 pmol of MVIIC may induce adverse effects on kidney tissue, suggesting a potential toxicity threshold.
