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Lower Serum Bilirubin and Uric Acid Concentrations in Patients with Parkinson’s Disease in China

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Abstract

The objective of the study is to investigate the correlation between bilirubin and uric acid (UA) concentrations and symptoms of Parkinson’s disease (PD) in Chinese population. A total of 425 PD patients and 460 controls were included in the current study. Patients were diagnosed by a neurologist and assessed using the Hoehn & Yahr (H&Y) scale. Venous blood samples were collected, and bilirubin and UA concentrations were analyzed. Compared to controls, indirect bilirubin (IBIL) and UA concentrations were lower in PD patients (P IBIL = 0.015, P UA = 0.000). Serum IBIL in different age subgroups and H&Y stage subgroups were also lower compared to the control group (P IBIL = 0.000, P UA = 0.000) but were not significantly different among these subgroups. Females in the control group had significantly lower serum IBIL and UA concentrations than males (P IBIL = 0.000, P UA = 0.000) and the PD group (P IBIL = 0.027, P UA = 0.000). In early PD (patients with <2-year medical history and no treatment), serum IBIL and UA concentrations were also lower than the controls (P IBIL = 0.013, P UA = 0.000). Although IBIL concentration was positively correlated with UA concentration in controls (R IBIL = 0.229, P IBIL = 0.004), this positive association was not observed in the PD group (R IBIL = −0.032, P IBIL = 0.724). Decreased levels of serum IBIL and UA were observed in PD patients. It is possible that individuals with decreased serum bilirubin and UA concentrations lack the endogenous defense system to prevent peroxynitrite and other free radicals from damaging and destroying dopaminergic cells in the substantia nigra. Our results provide a basis for further investigation into the role of bilirubin in PD.

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References

  1. Jenner, P. (2003). Oxidative stress in Parkinson’s disease [J]. Annals of Neurology, 53(suppl 3), S26–S36.

    Article  CAS  PubMed  Google Scholar 

  2. Ames, B. N., Cathcart, R., Schwiers, E., et al. (1981). Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: A hypothesis. Proceedings of the National Academy of Sciences of the United States of America, 78(11), 6858–6862.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Stocker, R., Yamamoto, Y., McDonagh, A. F., et al. (1987). Bilirubin is an antioxidant of possible physiological importance [J]. Science, 235(4792), 1043–1046.

    Article  CAS  PubMed  Google Scholar 

  4. Sedlak, T. W., Saleh, M., Higginson, D. S., et al. (2009). Bilirubin and glutathione have complementary antioxidant and cytoprotective roles [J]. Proceedings of the National Academy of Sciences of the United States of America, 106(13), 5171–5176.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Wu, T. W., Fung, K. P., & Yang, C. C. (1994). Unconjugated bilirubin inhibits the oxidation of human low density lipoprotein better than Trolox. Life Sciences, 54(25), 477–481.

    Article  Google Scholar 

  6. Frei, B., Stocker, R., & Ames, B. N. (1988). Antioxidant defenses and lipid peroxidation in human blood plasma. Proceedings of the National Academy of Sciences of the United States of America, 85(24), 9748–9752.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. McGeary, R. P., Szyczew, A. J., & Toth, I. (2003). Biological properties and therapeutic potential of bilirubin[J]. Mini-Reviews in Medicinal Chemistry, 3(3), 253–256.

    Article  CAS  PubMed  Google Scholar 

  8. Gong, L., Zhang, Q. L., Zhang, N., et al. (2012). Neuroprotection by urate on 6-OHDA-lesioned rat model of Parkinson’s disease: Linking to Akt/GSK3βsignaling pathway [J]. Journal of Neurochemistry, 123(5), 876–885.

    Article  CAS  PubMed  Google Scholar 

  9. Logroscino, G., Gao, X., Chen, H., et al. (2008). Dietary Iron intake and risk of Parkinson’s disease [J]. American Journal of Epidemiology, 168(12), 1381–1388.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Weisskopf, M. G., O’Reily, E., Chen, H., et al. (2007). Plasma urate and risk of Parkinson’S disease [J]. American Journal of Epidemiology, 166(5), 561–567.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Gopinathan, V., Miller, N. J., Milner, A. D., & Rice-Evans, C. A. (1994). Bilirubin and ascorbate antioxidant activity in neonatal plasma. FEBS Letters, 349, 197–200.

    Article  CAS  PubMed  Google Scholar 

  12. Dore, S., Takahashi, M., Ferris, C. D., et al. (1999). Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury [J]. Proceedings of the National Academy of Sciences of the United States of America, 96(5), 2445–2450.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Dore, S., & Snyde, S. H. (1999). Neuroprotective action of bilirubin against oxidative stress in primary hippocampal cultures [J]. Annals of the New York Academy of Sciences, 890, 167–172.

    Article  CAS  PubMed  Google Scholar 

  14. Tomaro, M. L., & Batlle, A. M. (2002). Bilirubin: Its role in cytoprotection against oxidative stress[J]. International Journal of Biochemistry & Cell Biology, 34(3), 216–220.

    Article  CAS  Google Scholar 

  15. Granato, A., Gores, G., Vilei, M. T., et al. (2003). Bilirubin inhibits bile acid induced apoptosis in rat hepatocytes[J]. Gut, 52(12), 1774–1778.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Dore, S., Sampei, K., Goto, S., et al. (1999). Heme oxygenase-2 is neuroprotective in cerebral ischemia. Molecular Medicine, 5, 656–663.

    CAS  PubMed  Google Scholar 

  17. Panahian, N., Huang, T., & Maines, M. D. (1999). Enhanced neuronal expression of the oxidoreductase-biliverdin reductase-after permanent focal cerebral ischemia. Brain Research, 850, 1–13.

    Article  CAS  PubMed  Google Scholar 

  18. De Vera, M., Rahman, M. M., RamKin, J., et al. (2008). Gout and the risk of Parkinson’s Disease: A cohort study[J]. Arthritis and Rheumatism, 59(11), 1549–1554.

    Article  PubMed  Google Scholar 

  19. Annanmaki, T., Muuronen, A., & Murros, K. (2007). Low plasma uric acid level in Parkinson’s disease [J]. Movement Disorders, 22(8), 1133–1137.

    Article  PubMed  Google Scholar 

  20. Gao, X., Chen, H., Choi, H. K., et al. (2008). Diet, urate, and Parkinson’s disease risk in men. American Journal of Epidemiology, 167(7), 831–838.

    Article  PubMed Central  PubMed  Google Scholar 

  21. De Lau, L. M., Koudstaal, P. J., Hofman, A., et al. (2005). Serum uric acid levels and the risk of Parkinson’s disease. Annals of Neurology, 58(5), 797–800.

    Article  PubMed  Google Scholar 

  22. Cipriani, S., Chen, X., & Schwarzschild, M. A. (2010). Urate: A novel biomarker of Parkinson’s disease risk, diagnosis and prognosis[J]. Biomarkers in Medicine, 4(5), 701–712.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Cipriani, S., Desjardins, C. A., Burdett, T. C., et al. (2012). Urate and its transgenic depletion modulate neuronal vulnerability in a cellular model of Parkinson’s disease [J]. PLoS One, 7(5), e37331.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Haberman, F., Tang, S. C., Arumugam, T. V., et al. (2007). Soluble neuroprotective antioxidant uric acid analogs ameliorate ischemic brain injury in mice [J]. Neuromolecular Medicine, 9(4), 315–323.

    Article  CAS  PubMed  Google Scholar 

  25. Schwarzschild, M. A., Schwid, S. R., Marek, K., et al. (2008). Serum urate as a predictor of clinical and radiographic progression in Parkinson’s disease J]. Archives of Neurology, 65(6), 716–723.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Schlesinger, I., & Schlesinger, N. (2008). Uric acid in Parkinson’s disease. Movement Disorders, 23, 1653–1657.

    Article  PubMed  Google Scholar 

  27. Jenner, P. (2007). Oxidative stress and Parkinson’s disease. Handbook of Clinical Neurology, 83, 507–520.

    PubMed  Google Scholar 

  28. Lotharius, J., Brundin, P. (2002). Pathogenesis of Parkinson’s disease: Dopamine, vesicles and alpha-synuclein. Nature Reviews Neuroscience, 3(12):932–42.

  29. Testa, C. M., Sherer, T. B., & Greenamyre, J. T. (2005). Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures[J]. Brain Research. Molecular Brain Research, 134(1), 109–118.

    Article  CAS  PubMed  Google Scholar 

  30. Tenhunen, R., Marver, H. S., & Schmid, R. (1968). The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proceedings of the National Academy of Sciences of the United States of America, 61, 748–755.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Schachter, D. (1957). Nature of the glucuronide in direct-reacting bilirubin. Science, 126, 507–508.

    Article  CAS  PubMed  Google Scholar 

  32. Nakagami, T., Toyomura, K., Kinoshita, T., et al. (1993). A beneficial role of bile pigments as an endougenous tissue protector: Anti-complement effects of biliverdin and conjugated bilirubin. Biophysica Acta, 1158, 189–193.

    Article  CAS  Google Scholar 

  33. Hunt, S. C., Kronenberg, F., Eckfeldt, J. H., et al. (2001). Association of plasma bilirubin with coronary heart disease and segregation of bilirubin as a major gene trait: The NHLBI family heart study [J]. Atherosclerosis, 154(3), 747–754.

    Article  CAS  PubMed  Google Scholar 

  34. Djousse, L., Levy, D., Cupples, L. A., et al. (2001). Total serum bilirubin and risk of cardiovascular disease in the Framingham offspring study[J]. American Journal of Cardiology, 87(10), 1196–1200.

    Article  CAS  PubMed  Google Scholar 

  35. Gourley, G. R. (1997). Bilirubin metabolism and kernicterus [J]. Advances in Pediatrics, 44, 173–229.

    CAS  PubMed  Google Scholar 

Download references

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Authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

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Qin, Xl., Zhang, Qs., Sun, L. et al. Lower Serum Bilirubin and Uric Acid Concentrations in Patients with Parkinson’s Disease in China. Cell Biochem Biophys 72, 49–56 (2015). https://doi.org/10.1007/s12013-014-0402-x

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