title: Peripheral biomarkers and exposure to manganese.
abstract: Biochemical mechanisms underlying manganese (Mn) toxicity include dopamine (DA) auto-oxidation and free radical generation with subsequent neuronal damage. A neuroendocrine approach based on the measurement of serum prolactin (PRL) has been proposed to assess the tonic inhibition of pituitary lactotrope cells by the tubero-infundibular DA system. Low level exposure to Mn oxides in industrial settings is associated with a shift in the distribution of serum PRL towards higher levels as compared to matched controls. The follow-up of a small cohort of workers from a ferro-manganese plant showed that the increased prevalence of abnormally high PRL values is stable over time. Although the mechanistic basis for their application is less straightforward, other biochemical markers such as dopamine beta hydroxylase and monoamine oxidase Type B, have also been assessed. Contrary to PRL levels, these markers cannot be recommended to monitor early biochemical effects of manganese exposure at the workplace. Early biochemical events can be modified by genetically determined individual differences. Owing to the possible role of a reduced capacity of glutathione conjugation as a risk factor increasing the susceptibility to the action of free radicals generated in the presence of Mn, the class mu glutathione S transferase (GSTM1) genotype has also been assessed in workers occupationally exposed. However, the GSTM1 null genotype does not appear to play an important role in the susceptibility to biochemical effects of Mn. A logistic model of the dose-response relationship based on urinary Mn as marker of exposure indicates that the benchmark dose corresponds to Mn levels as low as 0.4 microgram/l. This would imply that environmental exposure to Mn may contribute to abnormally high serum PRL in the general population.
authors.affiliation: Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma Medical School, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Smargiassi
authors.forename: A
authors.initials: A
authors.lastname: Mutti
mesh_terms: D015415:Biomarkers / Q000032:analysis* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008345:Manganese / Q000652:urine; D020149:Manganese Poisoning; D016273:Occupational Exposure / Q000009:adverse effects*; D011388:Prolactin / Q000097:blood*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D008345:Manganese; D011388:Prolactin; D005982:Glutathione Transferase