13-Systemic effects induced by intralesional injection of ω-conotoxin MVIIC after spinal cord injury in rats

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.

²Departament of Agrarian and Environmental Sciences, State University of Santa Cruz, Ilhéus, Bahia State, Brazil.

³National Institute of Sciences and Technology on Molecular Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais State, Brazil.

ABSTRACT

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.

Key words: Conus magus; Cone snail; Histopathology; Hematology; Biochemistry

Correspondence: kamoliveira@yahoo.com.br departamento de Clínica e Cirurgia Veterinária, Escola de Veterinária, Universidade Federalde Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG CEP 30123-970, Brasil Full list of author information is available at the end of the article

Competing interests

The authors declare that there are no competing interests.

Authors' contributions

KMO was the main responsible, participated in all stages of the experiment that was part of her master's project. CMOS contributed to the all surgeries and care for animals. MSLL participated in the study design, contributed to the surgeries and helped to draft the manuscript. IRR contributed to some surgeries and care of animals. FBF participated in the study design, contributed to the surgeries and helped to draft the manuscript. ALVFA took care of the animals, assisting with medications, bladder massage and clinica evaluation. SMNN assisted with the microscopic evaluation of tissue. GRM took care of the animals, assisting with medications, bladder massage and clinical evaluation. FFG helped with hematological examinations. MVG participated in the study design and coordination of the project. MMM participated in the study design and helped to draft the manuscript. EGM and MVG participated in the study design, coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

Ethics committee approval

All procedures of the current research were performed in accordance with ethical principles of animal experimentation adopted by the Ethics Committee on Animal Experimentation of the Federal University of Minas Gerais (CETEA/UFMG), which approved the present study under protocol n. 075/10.