Gas chromatography-mass spectrometry based metabolomics profile of hippocampus and cerebellum in mice after chronic arsenic exposure.

Intake of arsenic (As) via drinking water has been a serious threat to global public health. Though there are numerous reports of As neurotoxicity, its pathogenesis mechanisms remain vague especially its chronic effects on metabolic network. Hippocampus is a renowned area in relation to learning and memory, whilst recently, cerebellum is argued to be involved with process of cognition. Therefore, the study aimed to explore metabolomics alternations in these two areas after chronic As exposure, with the purpose of further illustrating details of As neurotoxicity. Twelve 3-week-old male C57BL/6J mice were divided into two groups, receiving deionized drinking water (control group) or 50 mg/L of sodium arsenite (via drinking water) for 24 weeks. Learning and memory abilities were tested by Morris water maze (MWM) test. Pathological and morphological changes of hippocampus and cerebellum were captured via transmission electron microscopy (TEM). Metabolic alterations were analyzed by gas chromatography-mass spectrometry (GC-MS). MWM test confirmed impairments of learning and memory abilities of mice after chronic As exposure. Metabolomics identifications indicated that tyrosine increased and aspartic acid (Asp) decreased simultaneously in both hippocampus and cerebellum. Intermediates (succinic acid) and indirect involved components of tricarboxylic acid cycle (proline, cysteine, and alanine) were found declined in cerebellum, indicating disordered energy metabolism. Our findings suggest that these metabolite alterations are related to As-induced disorders of amino acids and energy metabolism, which might therefore, play an important part in mechanisms of As neurotoxicity.

Aortic Artery and Cardiac Valve Calcification are Associated with Mortality in Chinese Hemodialysis Patients: A 3.5 Years Follow-up.

BACKGROUND: This study was to investigate the relationship among aortic artery calcification (AAC), cardiac valve calcification (CVC), and mortality in maintenance hemodialysis (MHD) patients. METHODS: All MHD patients in Shanghai Ruijin Hospital in July 2011 were included. To follow up for 42 months, clinical data, predialysis blood tests, echocardiography, and lateral lumbar X-ray plain radiography results were collected. Plasma FGF23 level was measured using a C-terminal assay. RESULTS: Totally, 110 MHD patients were involved in this study. Of which, 64 (58.2%) patients were male, the mean age was 55.2 ± 1.4 years old, and the median dialysis duration was 29.85 (3.0-225.5) months. About 25.5% of the 110 MHD patients had CVC from echocardiography while 61.8% of the patients had visible calcification of aorta from lateral lumbar X-ray plain radiography. After 42 months follow-up, 25 (22.7%) patients died. Kaplan-Meier analysis showed that patients with AAC or CVC had a significant greater number of all-cause and cardiovascular deaths than those without. In multivariate analyses, the presence of AAC was a significant factor associated with all-cause mortality (hazard ratio [HR]: 3.149, P = 0.025) in addition to lower albumin level and lower 25-hydroxy Vitamin D (25(OH)D) level. The presence of CVC was a significant factor associated with cardiovascular mortality (HR: 3.800, P = 0.029) in addition to lower albumin level and lower 25(OH)D level. CONCLUSION: Lateral lumbar X-ray plain radiography and echocardiography are simple methods to detect AAC and CVC in dialysis patients. The presence of AAC and CVC was independently associated with mortality in MHD patients. Regular follow-up by X-ray and echocardiography could be a useful method to stratify mortality risk in MHD patients.