Experimental Medicine and Toxicology Division, CSIR-Central Drug Research Institute, Lucknow-226031, UP, India.
Experimental Medicine and Toxicology Division, CSIR-Central Drug Research Institute, Lucknow-226031, UP, India.
Neurotoxicology. 2018 Mar;65:9-21. doi: 10.1016/j.neuro.2018.01.006. Epub 2018 Jan 31.
The study was conducted to evaluate the effect of minocycline against pesticide rotenone induced adverse effects in different rat brain regions. Assessment of oxidative stress, nitrite levels, degenerating neurons and level of cleaved caspase-3 was done in frontal cortex, mid brain, hippocampus and striatum regions of rat brain. In addition the expression profile of neuronal (MAP2), astrocytes (GFAP) and microglia (cd11b) markers was done after treatments. Rotenone induced DNA fragmentation was also assessed in all studied rat brain regions by utilizing comet assay. Rotenone administration caused significantly decreased level of glutathione along with increased level of nitrite and lipid peroxidation. Significant oxidative and nitrosative stress was also observed after rotenone administration which was considerably inhibited in minocycline treated rats in time dependent manner. Fluorojade staining and levels of cleaved caspase 3 showed the degeneration of neurons and apoptosis respectively in studied rat brain regions which were further inhibited with minocycline treatment. Rotenone administration caused significantly increased reactivity of astrocytes, microglia and altered neuronal morphology in rat brain regions which was also partially restored with minocycline treatment. In conclusion, present study showed that minocycline treatment attenuated the rotenone induced oxidative stress, nitrite level, degeneration of neurons, augmented glial reactivity and apoptosis.
该研究旨在评估米诺环素对不同大鼠脑区农药鱼藤酮诱导的不良影响的作用。评估氧化应激、亚硝酸盐水平、变性神经元和 cleaved caspase-3 水平在大鼠大脑的额皮质、中脑、海马和纹状体区域进行。此外,还在治疗后对神经元(MAP2)、星形胶质细胞(GFAP)和小胶质细胞(cd11b)标志物的表达谱进行了评估。还利用彗星试验评估了所有研究的大鼠脑区的鱼藤酮诱导的 DNA 片段化。鱼藤酮处理导致谷胱甘肽水平显著降低,同时亚硝酸盐和脂质过氧化水平升高。鱼藤酮处理后还观察到明显的氧化和硝化应激,米诺环素治疗以时间依赖性方式显著抑制了这种应激。氟乌杰德染色和 cleaved caspase 3 的水平分别显示了研究的大鼠脑区神经元的变性和细胞凋亡,米诺环素治疗进一步抑制了这种变性和凋亡。鱼藤酮处理导致星形胶质细胞、小胶质细胞的反应性显著增加,改变了大鼠脑区的神经元形态,米诺环素治疗部分恢复了这种形态。总之,本研究表明,米诺环素治疗减轻了鱼藤酮诱导的氧化应激、亚硝酸盐水平、神经元变性、神经胶质反应性增加和细胞凋亡。