Michalak Slawomir, Rybacka-Mossakowska Joanna, Ambrosius Wojciech, Gazdulska Joanna, Gołda-Gocka Iwona, Kozubski Wojciech, Ramlau Rodryg
Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, Poznan, Przybyszewskiego str. 49, 60-355 Poznan, Poland.
Department of Neurology, Poznan University of Medical Sciences, Przybyszewskiego Str. 49, 60-355 Poznan, Poland.
Dis Markers. 2016;2016:2895972. doi: 10.1155/2016/2895972. Epub 2016 Dec 4.
. To evaluate the involvement of glutamate metabolism in peripheral blood mononuclear cells (PBMC) in the development of neurological complications in lung cancer and during chemotherapy. . The prospective study included 221 lung cancer patients treated with chemotherapeutics. Neurological status and cognitive functions were evaluated at baseline and after 6-month follow-up. Glutamate level, the activities of glutaminase- (GLS-) glutamate synthetizing enzyme, glutamate dehydrogenase (GDH), and glutamate decarboxylase catalyzing glutamate degradation were analyzed in PBMC and in sera of lung cancer patients by means of spectrophotometric and colorimetric methods. . Chemotherapy of lung neoplasms induced increase of glutamate content in PBMC and its concentration in serum increased the activity of GDH in PBMC and decreased activity of glutaminase in PBMC. The changes in glutamate metabolism markers were associated with initial manifestation of neurological deficit in lung cancer patients and with new symptoms, which appear as a complication of chemotherapy. Moreover, the analyzed parameters of glutamate control correlated with a spectrum of cognitive functions measures in lung cancer patients. . We have demonstrated dysregulation in glutamate and glutamate metabolism controlling enzymes as promising indicators of risk for chemotherapy-induced neurological complications in lung cancer patients with particular emphasis on cognitive impairment.
评估谷氨酸代谢在外周血单个核细胞(PBMC)中与肺癌及化疗期间神经并发症发生发展的关系。前瞻性研究纳入了221例接受化疗的肺癌患者。在基线期及6个月随访后评估神经状态和认知功能。采用分光光度法和比色法分析肺癌患者PBMC及血清中的谷氨酸水平、谷氨酰胺酶-(GLS-)谷氨酸合成酶、谷氨酸脱氢酶(GDH)的活性以及催化谷氨酸降解的谷氨酸脱羧酶的活性。肺癌化疗导致PBMC中谷氨酸含量增加,血清中谷氨酸浓度升高,PBMC中GDH活性增加,谷氨酰胺酶活性降低。谷氨酸代谢标志物的变化与肺癌患者神经功能缺损的初始表现以及化疗并发症出现的新症状相关。此外,所分析的谷氨酸调控参数与肺癌患者的一系列认知功能指标相关。我们已证明谷氨酸及谷氨酸代谢调控酶的失调是肺癌患者化疗诱导神经并发症风险的有前景的指标,尤其强调认知障碍。