Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, Av. V. Carranza 2405, CP 78210 San Luis Potosí S.L.P, Mexico.
Toxicol Lett. 2012 Nov 30;215(2):110-8. doi: 10.1016/j.toxlet.2012.10.005. Epub 2012 Oct 17.
Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain.
砷毒性与其对一碳代谢的干扰有关，砷甲基化需要大量的 S-腺苷甲硫氨酸（SAM），而其再生的失败会影响甲基供体用于各种细胞功能。由于暴露于砷的动物表现出甲基化产物（如甲基精氨酸、髓鞘和轴突膜）的紊乱，本研究旨在探讨暴露于砷的大鼠脑中 SAM、胆碱和磷脂酰胆碱（PC）的改变是否与髓鞘改变和髓鞘碱性蛋白（MBP）免疫反应性有关。此外，还分析了这些代谢物、肝脏中甲基化改变的形态和生化标志物，肝脏是砷甲基化的主要部位。在通过饮水（3 ppm）长期暴露于砷的成年大鼠中，大脑中的 SAM、胆碱和 PC 浓度没有变化，但 SAM 和 PC 在肝脏中严重减少，同时胆碱显著增加。这些结果表明，胆碱在砷暴露中作为甲基供体发挥重要作用，这可能是砷暴露与其他环境因素共同作用时观察到肝脏损伤的基础。此外，重要的髓鞘和神经纤维改变，伴随着 MBP 免疫反应性下降 75%，与大脑中 SAM 缺乏无关。
