Skip to main content
SpringerLink
Log in

Implications of metal exposure and liver function in Parkinsonian patients resident in the vicinities of ferroalloy plants

  • Movement Disorders - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Valcamonica is an Italian valley where ferro-manganese industries have been active for a century and where an increased prevalence of parkinsonism was observed. A group of 93 patients (65 from Valcamonica, 28 from the reference area of Brescia city) and 76 controls (52 from Valcamonica, 24 from Brescia) were screened for serum Cu, Zn, Fe, Mn in blood (MnB) and urine (MnU), transferrin, peroxides, alanine (ALT) and aspartate (AST) transaminases and direct bilirubin. Test results were compared among groups according to the residential area and related to the disease severity. Valcamonica patients had a serum-increase of Cu, as well as of AST/ALT ratio, and a serum-decrease of Zn and Fe compared with other subgroups of cases and controls. Cases and controls from Valcamonica had higher MnB and MnU levels compared to cases and controls from Brescia. After controlling for the duration of illness, the Unified Parkinson’s Disease Rating Scale III domain correlated with serum Cu and AST/ALT ratio. Our results suggest the possibility that, in this area, a lifetime exposure to neurotoxicants and to Mn in particular, when accompanied to a subclinical liver dysfunction, may pose an increased risk for neurodegenerative disorders via metal metabolism (Cu, Zn, Fe) abnormalities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Abe A, Yamashita S, Noma A (1989) Sensitive direct colorimetric assay for copper in serum. Clin Chem 35:552–554

    PubMed  CAS  Google Scholar 

  • Alberti A, Bolognini L, Macciantelli D, Carratelli M (2000) The radical cation of N, N-Diethyl-para-phenylendiamine: a possible indicator of oxidative stress in biological samples. Res Chem Intermed 26:253–267

    Article  CAS  Google Scholar 

  • Apostoli P, Minoia C, Porru S, Ronchi A (1992) Determination of manganese in biological fluids by Zeeman GFAAS. In: Minoia C, Caroli S (eds) Applications of Zeeman graphite furnace absorption spectrometry in the chemical laboratory and in toxicology. Pergamon Press, London, pp 409–443

    Google Scholar 

  • ATSDR (2008) Toxicological Profile for Manganese Draft for Public Comment US Department of Health and Human Services. Public Health Service. Agency for Toxic Substances and Disease Registry. http://www.atsdr.cdc.gov/toxprofiles/tp151.html#bookmark01. Accessed on 12 June 2009

  • Burkhard PR, Delavelle J, Du Pasquier R, Spahr L (2003) Chronic parkinsonism associated with cirrhosis: a distinct subset of acquired hepatocerebral degeneration. Arch Neurol 60:521–528

    Article  PubMed  Google Scholar 

  • Cersosimo MG, Koller WC (2006) The diagnosis of manganese-induced parkinsonism. Neurotoxicology 27(3):340–346

    Article  PubMed  CAS  Google Scholar 

  • Correia JP, Alves PS, Camilo EA (1981) SGOT–SGPT ratios. Dig Dis Sci 26:284

    Article  PubMed  CAS  Google Scholar 

  • Dick FD, De Palma G, Ahmadi A, Scott NW, Prescott GJ, Bennett J, Semple S, Dick S, Counsell C, Mozzoni P, Haites N, Wettinger SB, Mutti A, Otelea M, Seaton A, Söderkvist P, Felice A (2007) Geoparkinson study group. Environmental risk factors for Parkinson’s disease and parkinsonism: the Geoparkinson study. Occup Environ Med 64:666–672

    Article  PubMed  CAS  Google Scholar 

  • Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, Marshall FJ, Ravina BM, Schifitto G, Siderowf A, Tanner CM (2007) Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 68:384–386

    Article  PubMed  CAS  Google Scholar 

  • Elbaz A, Bower JH, Maraganore DM, McDonnell SK, Peterson BJ, Ahlskog JE, Schaid DJ, Rocca WA (2002) Risk tables for parkinsonism and Parkinson’s disease. J Clin Epidemiol 55:25–31

    Article  PubMed  Google Scholar 

  • Gilbert RO (1987) Statistical methods for environmental pollution monitoring. Van Nostrand Reinhold, New York

  • Guilarte TR, Chen MK, McGlothan JL, Verina T, Wong DF, Zhou Y, Alexander M, Rohde CA, Syversen T, Decamp E, Koser AJ, Fritz S, Gonczi H, Anderson DW, Schneider JS (2006) Nigrostriatal dopamine system dysfunction and subtle motor deficits in manganese-exposed non-human primates. Exp Neurol 202:381–390

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto M, Takeda A, Hsu LJ, Takenouchi T, Masliah E (1999) Role of cytochrome c as a stimulator of alpha-synuclein aggregation in Lewy body disease. J Biol Chem 274:28849–28852

    Article  PubMed  CAS  Google Scholar 

  • Hegde ML, Shanmugavelu P, Vengamma B, Rao TS, Menon RB, Rao RV, Rao KS (2004) Serum trace element levels and the complexity of inter-element relations in patients with Parkinson’s disease. J Trace Elem Med Biol 18:163–171

    Article  PubMed  CAS  Google Scholar 

  • Higgins T (1981) Novel chromogen for serum iron determinations. Clin Chem 27:1619–1620

    PubMed  CAS  Google Scholar 

  • Hoogenraad T (2001) Wilson’s disease. Intermed Medical Publishers, Amsterdam/Rotterdam

    Google Scholar 

  • Huber PJ (1981) Robust statistics. Wiley, New York

  • Jankovic J (2005) Searching for a relationship between manganese and welding and Parkinson’s disease. Neurology 2864:2021–2028

    Article  Google Scholar 

  • Kang JH, Kim KS (2003) Enhanced oligomerization of the alpha-synuclein mutant by the Cu, Zn-superoxide dismutase and hydrogen peroxide system. Mol Cells 15:87–93

    PubMed  CAS  Google Scholar 

  • Kikuchi A, Takeda A, Onodera H, Kimpara T, Hisanaga K, Sato N, Nunomura A, Castellani RJ, Perry G, Smith MA, Itoyama Y (2002) Systemic increase of oxidative nucleic acid damage in Parkinson’s disease and multiple system atrophy. Neurobiol Dis 9:244–248

    Article  PubMed  CAS  Google Scholar 

  • Klos KJ, Ahlskog JE, Kumar N, Cambern S, Butz J, Burritt M, Fealey RD, Cowl CT, Parisi JE, Josephs KA (2006) Brain metal concentrations in chronic liver failure patients with pallidal T1 MRI hyperintensity. Neurology 67:1984–1989

    Article  PubMed  CAS  Google Scholar 

  • Lubin JH, Colt JS, Camann D, Davis S, Cerhan JR, Severson RK, Bernstein L, Hartge P (2004) Epidemiologic evaluation of measurement data in the presence of detection limits. Environ Health Perspect 112:1691–1696

    PubMed  CAS  Google Scholar 

  • Lucchini RG, Albini E, Benedetti L, Borghesi S, Coccaglio R, Malara EC, Parrinello G, Garattini S, Resola S, Alessio L (2007a) High prevalence of Parkinsonian disorders associated to manganese exposure in the vicinities of ferroalloy industries. Am J Ind Med 50:788–800

    Article  PubMed  CAS  Google Scholar 

  • Lucchini R, Albini E, Benedetti L, Zoni S, Caruso A, Nan E, Pasqualetti P, Rossini PM, Binetti G, Benussi L, Parrinello G, Gasparotti R, Padovani A, Draicchio F, Alessio L (2007b) Neurological and neuropsychological features in parkinsonian patients exposed to neurotoxic metals. G Ital Med Lav Ergon 29:280–281

    PubMed  CAS  Google Scholar 

  • Lucchini R, Squitti R, Albini E, Benedetti L, Borghesi S, Nan E, Draicchio F, Coccaglio R, Alessio L (2008) Manganese exposure as a determinant of Parkinsonian damage. Cell Biol Toxicol 24:445–448

    Google Scholar 

  • McGreevy KM, Lipsitz SR, Linder JA, Rimm E, Hoel DG (2009) Using median regression to obtain adjusted estimates of central tendency for skewed laboratory and epidemiologic data. Clin Chem 55:165–169

    Article  PubMed  CAS  Google Scholar 

  • Miatto O, Casaril M, Gabrielli GB, Nicoli N, Bellisola G, Corrocher R (1985) Diagnostic and prognostic value of serum copper and plasma fibrinogen in hepatic carcinoma. Cancer 55:774–778

    Article  PubMed  CAS  Google Scholar 

  • Oestreicher P, Cousins RJ (1985) Copper and zinc absorption in the rat: mechanism of mutual antagonism. J Nutr 1985(115):159–166

    Google Scholar 

  • Paik SR, Shin HJ, Lee JH, Chang CS, Kim J (1999) Copper (II)-induced self oligomerization of alpha-synuclein. Biochem J 340:821–828

    Article  PubMed  CAS  Google Scholar 

  • Poo JL, Romero RR, Robles JA, Montemayor AC, Isoard F, Estanes A, Uribe M (1997) Diagnostic value of the copper/zinc ratio in digestive cancer: a case control study. Arch Med Res 28:259–263

    PubMed  CAS  Google Scholar 

  • Pramoolsinsap C, Promvanit N, Komindr S, Lerdverasirikul P, Srianujata S (1994) Serum trace metals in chronic viral hepatitis and hepatocellular carcinoma in Thailand. J Gastroenterol 29:610–615

    Article  PubMed  CAS  Google Scholar 

  • Schmucker DL (2005) Age-related changes in liver structure and function: implications for disease? Exp Gerontol 40(8–9):650–659

    Article  PubMed  CAS  Google Scholar 

  • Sharp P (2004) The molecular basis of copper and iron interactions. Proc Nutr Soc 63:563–569

    Article  PubMed  CAS  Google Scholar 

  • Shults CW, Haas RH, Passov D, Beal MF (1997) Coenzyme Q10 levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects. Ann Neurol 42:261–264

    Article  PubMed  CAS  Google Scholar 

  • Skikne BS, Flowers CH, Cole JD (1990) Serum transferrin receptor, a quantitative measure of tissue iron deficiency. Blood 75:1870–1876

    PubMed  CAS  Google Scholar 

  • Slot C (1965) The significance of the systemic arteriovenous difference in creatinine clearance determinations. Scand J Clin Lab Invest 17:201–208

    Article  PubMed  CAS  Google Scholar 

  • Squitti R, Ventriglia M, Barbati G, Cassetta E, Ferreri F, Dal Forno G, Ramires S, Zappasodi F, Rossini PM (2007) ‘Free’ copper in serum of Alzheimer’s disease patients correlates with markers of liver function. J Neural Transm 114:1589–1594

    Article  PubMed  CAS  Google Scholar 

  • Szasz G (1974) New substrates for measuring gamma-glutamyl transpeptidase activity. Z Klin Chem Klin Biochem 12:228

    PubMed  CAS  Google Scholar 

  • Tobin J (1958) Estimation of relationship for limited dependent variables. Econometrica 26:24–36

    Article  Google Scholar 

  • Wedler FC, Ley BW (1990) Cu(II) and Zn(II) ions alter the dynamics and distribution of Mn(II) in cultured chick glial cells. Neurochem Res 15:1221–1228

    Article  PubMed  CAS  Google Scholar 

  • Wermuth L, Bech S, Petersen MS, Joensen P, Weihe P, Grandjean P (2008) Prevalence and incidence of Parkinson’s disease in The Faroe Islands. Acta Neurol Scand 118:126–131

    Article  PubMed  CAS  Google Scholar 

  • Winikates J, Jankovic J (1999) Clinical correlates of vascular parkinsonism. Arch Neurol 56:98–102

    Article  PubMed  CAS  Google Scholar 

  • Zacco A, Resola S, Lucchini R, Albini E, Zimmerman N, Guazzetti S, Bontempi E (2009) Analysis of settled dust with X-ray fluorescence for exposure assessment of metals in the province of Brescia, Italy. J Env Monit. doi:10.1039/B906430C

Download references

Acknowledgments

This study was supported by the National Institute for Occupational Safety and Prevention of Italy (ISPESL), with the grant PFA/DML/UO4/2002 “Markers biochimici del Morbo di Parkinson di possible origine occupazionale” and by a grant from the AFaR Foundation-Hosp. Fatebenefratelli Rome, Italy. It was also partially supported by the EU through its Sixth Framework Programme for RTD (contract no FOOD-CT-2006-016253), which reflects only the author’s views. The European Community is not liable for any use that may be made of the information contained therein.

Author information

Authors and Affiliations

  1. AFaR Department of Neuroscience, AFaR-Fatebenefratelli Hospital, Isola Tiberina, 00186, Rome, Italy

    Rosanna Squitti & P. M. Rossini

  2. Neurology, Università Campus Biomedico, Rome, Italy

    Rosanna Squitti, G. Gorgone, S. Bucossi, J. M. Melgari & P. M. Rossini

  3. Medical Statistics and Information Technology, AFaR–FBF Hospital, Isola Tiberina, Rome, Italy

    V. Panetta

  4. Section of Occupational Health and Industrial Hygiene, University of Brescia, Brescia, Italy

    R. Lucchini, E. Albini, L. Alessio & A. Alberici

  5. IRCCS “Center S. Giovanni di Dio-FBF”, Brescia, Italy

    L. Benussi & G. Binetti

  6. Casa di Cura San Raffaele, Cassino & IRCCS San Raffaele Pisana, Rome, Italy

    P. M. Rossini

  7. National Institute for Work Prevention and Safety ISPESL, Rome, Italy

    F. Draicchio

Authors
  1. Rosanna Squitti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Gorgone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Panetta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Lucchini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Bucossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. Albini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. Alessio
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. Alberici
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J. M. Melgari
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. L. Benussi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. G. Binetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. P. M. Rossini
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. F. Draicchio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rosanna Squitti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Squitti, R., Gorgone, G., Panetta, V. et al. Implications of metal exposure and liver function in Parkinsonian patients resident in the vicinities of ferroalloy plants. J Neural Transm 116, 1281–1287 (2009). https://doi.org/10.1007/s00702-009-0283-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-009-0283-0

Keywords

Search

Navigation