Departamento 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.
Departament of Agrarian and Environmental Sciences, State University of Santa Cruz, Ilhéus, Bahia State, Brazil.
J Venom Anim Toxins Incl Trop Dis. 2014 Apr 16;20:15. doi: 10.1186/1678-9199-20-15. eCollection 2014.
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.
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.
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.
钙通道阻滞剂,如芋螺毒素,已显示出在减少脑和脊髓损伤方面的巨大潜力。在体外脑和脊髓缺血模型中分析的 MVIIC 神经保护作用表明,这种毒素在预防脊髓创伤后损伤方面可能具有潜在作用。然而,以前的 MVIIC 临床研究表明,临床副作用可能限制该药物的有效性,并且尚未研究其全身作用。因此,本研究旨在研究 MVIIC 对器官的潜在毒性作用,并评估接受脊髓损伤治疗的大鼠的临床和血液特征以及用这种海洋毒素治疗的大鼠。大鼠在脊髓损伤后接受 MVIIC(15、30、60 或 120 pmol)皮内治疗。毒素给药 7 天后,对肾脏、大脑、肺、心脏、肝脏、肾上腺、肌肉、胰腺、脾脏、胃和肠进行组织病理学检查。此外,从大鼠采集的血液样本用于测试任何血液学或生化变化。
临床、血液学和生化评估显示所有组均无明显异常,即使在高剂量组也是如此。除了 120 pmol 剂量的肾脏退行性变化外,器官没有明显改变。
这些发现表明,MVIIC 在 15、30 和 60 pmol 时在脊髓损伤后皮内给药是安全的,并且可以进一步研究其神经保护作用。然而,120 pmol 剂量的 MVIIC 可能会对肾脏组织产生不利影响。