Elevated asymmetric dimethylarginine levels in manganese-exposed welders

Aims: Although manganese (Mn) toxicity has been reported to cause cardiovascular problems, the underlying mechanism has not been fully elucidated. Derivatives of methylated arginine inhibit nitric oxide synthesis leading to the formation of cardiovascular diseases. The aim of this study was to determine the relation between serum methylated arginine levels and Mn exposure. Materials and methods: Whole blood was collected from 59 nonexposed control subjects and 54 Mn-exposed welders. Whole blood Mn was analyzed by inductively coupled plasma - mass spectrometer on Agilent 7700 (Agilent Technologies). Serum aspartate transaminase (AST), alanine transaminase (ALT), urea, creatinine, and C-reactive protein (CRP) were analyzed by spectrophotometric methods on Roche E170 Modular System (Roche Diagnostics, Mannheim, Germany) and immunoturbidimetric method on Abbott C8000, respectively. Prolidase was analyzed by colorimetric method. Erythrocyte sedimentation rate (ESR) was calculated on Alifax sedimentation device (Padova, Italy). Serum methylated arginines were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (API 3200, ABSCIEX). Results: There was no statistically significant difference between serum prolidase activities for controls and Mn-exposed welders (1,010 +/- 137 and 1,018 +/- 154, respectively, p = 0.778). Serum asymmetric dimethylarginine (ADMA) levels (0.23 +/- 0.04 vs. 0.17 +/- 0.03 mu mol/L, p < 0.001), serum symmetric dimethylarginine (SDMA) levels (0.33 +/- 0.07 vs. 0.22 +/- 0.04 mu mol/L, p < 0.001) were found to be statistically higher in welders compared to controls, respectively. There was a significant decrease in serum arginine/ADMA ratio (412 +/- 300 vs. 744 +/- 376, p < 0.001) in welders compared to controls, respectively. There was a significantly positive correlation between whole blood Mn levels and serum ADMA (r = 0.570, p < 0.001) and SDMA (r = 0.451, p < 0.001) and a negative correlation for arginine/ADMA ratio (r = -0.214, p < 0.05). Serum methylated arginine levels might be related to cardiovascular effects of Mn exposure.