Dr. Ron’s Research Review – May 9, 2018

©

This week’s research review focuses on prolactin as a peripheral marker of manganese neurotoxicity.

Urinary and Blood Manganese

Manganese in total blood (MnB) and urinary manganese (MnU) can discriminate groups of occupationally exposed workers from groups of nonexposed subjects. MnB is also related to the intensity of external exposure on a linear relationship, but given a high variability, it is not suitable for individual biological monitoring. Therefore, further research should focus on more accurate biomarkers of Mn exposure. (Apostoli et al., 2000)

Prolactin and Metals

A study assessed the relationship between metal concentrations in blood and serum prolactin (PRL) and thyrotropin (TSH) levels, markers of dopaminergic, and thyroid function, respectively, among men participating in a study of environmental influences on male reproductive health. PRL was inversely associated with arsenic, cadmium, copper, lead, manganese, molybdenum, and zinc, but positively associated with chromium. Lead and copper were associated with non-monotonic decrease in TSH, while arsenic was associated with a dose-dependent increase in TSH. (Meeker et al., 2009)

Prolactin and Manganese

Excessive exposure to Mn induces neurotoxicity, referred to as manganism. Exposure assessment relies on Mn blood and urine analyses, both of which show poor correlation to exposure. Accordingly, there is a critical need for better surrogate biomarkers of Mn exposure. This study demonstrates that peripheral blood level is a poor indicator of Mn brain accumulation and exposure. Mn reduces GSH brain levels, likely reflecting oxidative stress. Mn increases blood prolactin levels, indicating changes in the integrity of the dopaminergic system. Taken together these results suggest that peripheral prolactin levels may serve as reliable predictive biomarkers of Mn neurotoxicity. (Marreilha Dos Santos et al., 2011)

 

Dr. Ron


 

Articles

Are current biomarkers suitable for the assessment of manganese exposure in individual workers
            (Apostoli et al., 2000) Download
BACKGROUND:  Whole blood and urinary manganese have been measured in occupational and environmental studies for the assessment of exposure. The aim of this study was to assess the relationship between the airborne concentrations of manganese and these biological indicators. METHODS:  Environmental and biological monitoring was performed in a group of 94 employees in a ferroalloy production, who were exposed to manganese (Mn) oxides (MnO(2) and Mn(3)O(4)). The results were compared with those from a control group of 87 subjects not exposed to Mn. RESULTS:  Mn exposure levels ranged between 5 and 740 micrograms/m(3), with arithmetic and geometric mean and median values being 202.6, 97.6, and 150 micrograms/m(3), respectively. Arithmetic and geometric means for Mn in total blood (MnB) were, respectively, 10.3+/-3.8 and 9.7 micrograms/L in the exposed and 5.9+/-1.7 and 5.7 micrograms/L in the controls. For urinary Mn (MnU), arithmetic and geometric means were, respectively, 4.9+/-3.6 and 3. 8 micrograms/L in the exposed and 1.2+/-1.4 and 0.7 micrograms/L in the controls. On a group comparison, a significant relationship was found between high and low exposed subgroups, identified according to Mn atmospheric concentrations (MnA), for both MnB (F value=38.0, P > 0.0001) and MnU (F value=36.1, P > 0.0001). On a linear relationship, a correlation was observed between MnA and MnB (r=0. 34; r(2)=0.112; P=0.001), whereas no association was found between MnA and MnU. A significant relationship emerged also between MnB and MnU (r=0.48, r(2)=0.23, P < 0.0001). No association was observed between an index of cumulative exposure and the biological indicators of exposure. CONCLUSIONS:  These results confirm that MnB and MnU can discriminate groups of occupationally exposed workers from groups of nonexposed subjects. MnB is also related to the intensity of external exposure on a linear relationship, but given a high variability, it is not suitable for individual biological monitoring. Therefore, further research should focus on more accurate biomarkers of Mn exposure.

Prolactin is a peripheral marker of manganese neurotoxicity.
            (Marreilha Dos Santos et al., 2011) Download
UNLABELLED:  Excessive exposure to Mn induces neurotoxicity, referred to as manganism. Exposure assessment relies on Mn blood and urine analyses, both of which show poor correlation to exposure. Accordingly, there is a critical need for better surrogate biomarkers of Mn exposure. The aim of this study was to examine the relationship between Mn exposure and early indicators of neurotoxicity, with particular emphasis on peripheral biomarkers. Male Wistar rats (180-200g) were injected intraperitoneally with 4 or 8 doses of Mn (10mg/kg). Mn exposure was evaluated by analysis of Mn levels in brain and blood along with biochemical end-points (see below). RESULTS:  Brain Mn levels were significantly increased both after 4 and 8 doses of Mn compared with controls (p<0.001). Blood levels failed to reflect a dose-dependent increase in brain Mn, with only the 8-dose-treated group showing significant differences (p<0.001). Brain glutathione (GSH) levels were significantly decreased in the 8-dose-treated animals (p<0.001). A significant and dose-dependent increase in prolactin levels was found for both treated groups (p<0.001) compared to controls. In addition, a decrease in motor activity was observed in the 8-dose-treated group compared to controls. CONCLUSIONS:  (1) The present study demonstrates that peripheral blood level is a poor indicator of Mn brain accumulation and exposure; (2) Mn reduces GSH brain levels, likely reflecting oxidative stress; (3) Mn increases blood prolactin levels, indicating changes in the integrity of the dopaminergic system. Taken together these results suggest that peripheral prolactin levels may serve as reliable predictive biomarkers of Mn neurotoxicity.

Multiple metals predict prolactin and thyrotropin (TSH) levels in men.
            (Meeker et al., 2009) Download
Exposure to a number of metals can affect neuroendocrine and thyroid signaling, which can result in adverse effects on development, behavior, metabolism, reproduction, and other functions. The present study assessed the relationship between metal concentrations in blood and serum prolactin (PRL) and thyrotropin (TSH) levels, markers of dopaminergic, and thyroid function, respectively, among men participating in a study of environmental influences on male reproductive health. Blood samples from 219 men were analyzed for concentrations of 11 metals and serum levels of PRL and TSH. In multiple linear regression models adjusted for age, BMI and smoking, PRL was inversely associated with arsenic, cadmium, copper, lead, manganese, molybdenum, and zinc, but positively associated with chromium. Several of these associations (Cd, Pb, Mo) are consistent with limited studies in humans or animals, and a number of the relationships (Cr, Cu, Pb, Mo) remained when additionally considering multiple metals in the model. Lead and copper were associated with non-monotonic decrease in TSH, while arsenic was associated with a dose-dependent increase in TSH. For arsenic these findings were consistent with recent experimental studies where arsenic inhibited enzymes involved in thyroid hormone synthesis and signaling. More research is needed for a better understanding of the role of metals in neuroendocrine and thyroid function and related health implications.

 

References

 

Apostoli, P, R Lucchini, and L Alessio (2000), ‘Are current biomarkers suitable for the assessment of manganese exposure in individual workers’, Am J Ind Med, 37 (3), 283-90. PubMed: 10642418
Marreilha Dos Santos, AP, et al. (2011), ‘Prolactin is a peripheral marker of manganese neurotoxicity.’, Brain Res, 1382 282-90. PubMed: 21262206
Meeker, JD, et al. (2009), ‘Multiple metals predict prolactin and thyrotropin (TSH) levels in men.’, Environ Res, 109 (7), 869-73. PubMed: 19595304