Departamento de Neurociencias, UNAM FES Iztacala, Tlalnepantla, México.
Departamento de Biología Celular y Tisular, Facultad de Medicina, UNAM, México City, México.
Int J Exp Pathol. 2018 Aug;99(4):180-188. doi: 10.1111/iep.12285. Epub 2018 Sep 9.
Carnosine (β-alanyl-L-histidine) is synthesized in the olfactory system, has antioxidant activity as a scavenger of free radicals and has been reported to have neuroprotective action in diseases which have been attributed to oxidative damage. In neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, impairment of olfactory function has been described. Vanadium derivatives are environmental pollutants, and its toxicity has been associated with oxidative stress. Vanadium toxicity on the olfactory bulb was reported previously. This study investigates the neuroprotective effect of carnosine on the olfactory bulb in a mice model of vanadium inhalation. Male mice were divided into four groups: vanadium pentoxide (V O ) [0.02 mol/L] inhalation for one hour twice a week; V O inhalation plus 1 mg/kg of carnosine administered daily; carnosine only, and the control group that inhaled saline. The olfactory function was evaluated using the odorant test. Animals were sacrificed four weeks after exposure. The olfactory bulbs were dissected and processed using the rapid Golgi method; cytological and ultrastructural analysis was performed and malondialdehyde (MDA) concentrations were measured. The results showed evidence of olfactory dysfunction caused by vanadium exposure and also an increase in MDA levels, loss of dendritic spines and necrotic neuronal death in the granule cells. But, in contrast, vanadium-exposed mice treated with carnosine showed an increase in dendritic spines and a decrease in neuronal death and in MDA levels when compared with the group exposed to vanadium without carnosine. These results suggest that dendritic spine loss and ultrastructural alterations in the granule cells induced by vanadium are mediated by oxidative stress and that carnosine may modulate the neurotoxic vanadium action, improving the olfactory function.
肌肽（β-丙氨酰-L-组氨酸）在嗅觉系统中合成，具有抗氧化活性，可作为自由基清除剂，并且已被报道在归因于氧化损伤的疾病中具有神经保护作用。在神经退行性疾病中，如帕金森氏病和阿尔茨海默氏病，已经描述了嗅觉功能的损害。钒衍生物是环境污染物，其毒性与氧化应激有关。先前已经报道了钒对嗅球的毒性。本研究调查了肌肽对吸入钒的小鼠模型中嗅球的神经保护作用。雄性小鼠分为四组：五氧化二钒（V O ）[0.02 mol/L]每周两次吸入一小时；V O 吸入加 1 mg/kg 肌肽每天给药；仅肌肽和吸入生理盐水的对照组。使用气味测试评估嗅觉功能。暴露后四周处死动物。嗅球被解剖并使用快速高尔基体方法处理；进行细胞学和超微结构分析，并测量丙二醛（MDA）浓度。结果表明，嗅球暴露导致嗅觉功能障碍，并增加 MDA 水平，颗粒细胞中树突棘丢失和坏死性神经元死亡。但是，相反，与未用肌肽暴露于钒的组相比，用肌肽处理的暴露于钒的小鼠显示出树突棘增加，神经元死亡减少和 MDA 水平降低。这些结果表明，钒诱导的颗粒细胞中树突棘丢失和超微结构改变是由氧化应激介导的，并且肌肽可能调节神经毒性钒的作用，从而改善嗅觉功能。
