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.
Similar content being viewed by others
References
Jenner, P. (2003). Oxidative stress in Parkinson’s disease [J]. Annals of Neurology, 53(suppl 3), S26–S36.
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.
Stocker, R., Yamamoto, Y., McDonagh, A. F., et al. (1987). Bilirubin is an antioxidant of possible physiological importance [J]. Science, 235(4792), 1043–1046.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dore, S., Sampei, K., Goto, S., et al. (1999). Heme oxygenase-2 is neuroprotective in cerebral ischemia. Molecular Medicine, 5, 656–663.
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.
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.
Annanmaki, T., Muuronen, A., & Murros, K. (2007). Low plasma uric acid level in Parkinson’s disease [J]. Movement Disorders, 22(8), 1133–1137.
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.
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.
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.
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.
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.
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.
Schlesinger, I., & Schlesinger, N. (2008). Uric acid in Parkinson’s disease. Movement Disorders, 23, 1653–1657.
Jenner, P. (2007). Oxidative stress and Parkinson’s disease. Handbook of Clinical Neurology, 83, 507–520.
Lotharius, J., Brundin, P. (2002). Pathogenesis of Parkinson’s disease: Dopamine, vesicles and alpha-synuclein. Nature Reviews Neuroscience, 3(12):932–42.
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.
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.
Schachter, D. (1957). Nature of the glucuronide in direct-reacting bilirubin. Science, 126, 507–508.
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.
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.
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.
Gourley, G. R. (1997). Bilirubin metabolism and kernicterus [J]. Advances in Pediatrics, 44, 173–229.
Conflict of interest
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12013-014-0402-x