Colín-Barenque L, Martínez-Hernández M G, Baiza-Gutman L A, Avila-Costa M R, Ordóñez-Librado J L, Bizarro-Nevares P, Rodriguez-Lara V, Piñón-Zarate G, Rojas-Lemus M, Mussali-Galante P, Fortoul T I
Departamento de Neurociencias, UNAM Iztacala, Av. De los Barrios # 1, Los Reyes Iztacala, Tlalnepantla, CP 54090 Edo. México, Mexico.
J Appl Toxicol. 2008 Aug;28(6):718-23. doi: 10.1002/jat.1326.
Vanadium (V) derivatives are well-known environmental pollutants and its toxicity has been related with oxidative stress. Toxicity after vanadium inhalation on the substantia nigra, corpus striatum, hippocampus and ependymal epithelium was reported previously. The purpose of this study was to analyse the role of matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) in the changes observed in brain tissue after chronic V inhalation. Mice were exposed to vaporized, vanadium pentoxide 0.02 m in deionized water for 1 h twice a week, and killed at 1 h, 1, 2 and 4 weeks after exposure. The brain was removed and the olfactory bulb, prefrontal cortex, striatum and hippocampus were dissected and the MMP content was obtained by zymography. The results showed that MMP-9 increased in all the structures at the end of the exposure, although in the hippocampus this increment was evident after 1 week of exposure. When MMP-2 was analysed in the olfactory bulb and prefrontal cortex it remained unchanged throughout the whole exposure, while in the hippocampus it increased at week 4, while in the striatum MMP-2 increased from the second week only, through the whole experiment. These results demonstrate that V increased MMPs in different structures of the CNS and this change might be associated with the previously reported modifications, such as dendritic spine loss and neuronal cell death. The modifications in MMPs could be related with blood-brain barrier (BBB) disruption which was reported previously. Oxidative stress might also be involved in the activation of these gelatinases as part of the different mechanisms which take place in V toxicity in the CNS.
钒（V）衍生物是众所周知的环境污染物，其毒性与氧化应激有关。此前已有关于吸入钒后对黑质、纹状体、海马体和室管膜上皮毒性的报道。本研究的目的是分析基质金属蛋白酶2（MMP - 2）和9（MMP - 9）在慢性吸入钒后脑组织中观察到的变化中的作用。将小鼠暴露于在去离子水中汽化的五氧化二钒0.02 m，每周两次，每次1小时，并在暴露后1小时、1周、2周和4周处死。取出大脑，解剖嗅球、前额叶皮质、纹状体和海马体，通过酶谱法测定MMP含量。结果表明，暴露结束时所有结构中的MMP - 9均增加，尽管在海马体中这种增加在暴露1周后才明显。当在嗅球和前额叶皮质中分析MMP - 2时，在整个暴露过程中其保持不变，而在海马体中它在第4周增加，而在纹状体中MMP - 2仅从第2周开始增加，贯穿整个实验。这些结果表明，钒增加了中枢神经系统不同结构中的MMPs，这种变化可能与先前报道的改变有关，如树突棘丢失和神经元细胞死亡。MMPs的改变可能与先前报道的血脑屏障（BBB）破坏有关。氧化应激也可能作为中枢神经系统中钒毒性发生的不同机制的一部分参与这些明胶酶的激活。
