Occupational exposure to manganese (Mn) causes a Parkinson-type disorder called Manganism, a neurodegenerative disease currently without reliable biomarkers for body burden estimation and for pre-symptomatic toxicity assessment. Data in literature suggest that Mn deposited in bone accounts for 43% of total body Mn. The objective of this study was to determine if bone Mn levels were parallel to Mn concentrations in brain regions known to be the targets of Mn toxicity. Groups of rats (6-7 each) received daily dose of 50 mg Mn/kg as MnCl2 PO for 0, 2, 4, 6, 8 or 10 weeks before tissue dissection. The metal concentrations of Mn, zinc (Zn), iron (Fe), and copper (Cu) in bone tissues, body fluids, brain tissues, as well as other organs were analyzed by atomic absorption spectrophotometry. Following Mn exposure, bone tissues including femur, tibia, humerus and skull bones showed a dose-time-dependent increase in Mn concentrations, with 1.0-1.6 microg/g of bone mass at week 10, which were about 2.3-3.6 fold higher than those in controls (~0.4 microg/g) at day 0 (p<0.01). A statistically significant relationship exists between bone Mn concentrations and Mn levels in brain tissues such as striatum (r=0.755, p<0.001), hippocampus (r=0.782, p<0.001) and choroid plexus (0.652, p<0.001), and in brain fluid such as cerebrospinal fluid (r=0.720, p<0.001). Interestingly, in vivo exposure to Mn also led to significantly increased Fe (152-372%) and Zn (194-230%) concentrations in bone tissues except the skull bones, with no statistically significant effect on bone Cu (58-95%). These results suggest that bone is a significant storage site for body Mn; the good correlation between bone Mn and brain Mn alludes to bone Mn being an internal source of Mn long-term exposure. Further experimentation for noninvasive quantitation of Mn in bone is well warranted for Mn neurotoxicological research.
Toxicology; Laboratory-animals; Exposure-levels; Dose-response; Manganese-compounds; Neurological-system; Neurophysiological-effects; Neurotoxic-effects; Neurotoxicology; Body-burden; Body-regions; Bone-structure; Brain-matter; Tissue-culture; Metal-compounds; Body-fluids; In-vivo-study; Pharmacodynamics;
Author Keywords: Manganese; Manganism; Biomarker; Bone; Correlation; Pharmacokinetics
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, San Antonio, Texas, March 10-14, 2013