BACKGROUND AND PURPOSE: Oxidative stress is a central pathogenic mechanism of Parkinson's disease (PD), and the heme oxygenase (HO) bilirubin pathway is one of the main mammalian antioxidative defences. Indeed, there is growing evidence of HO-bilirubin upregulation from early phases of PD. Our aim was to investigate bilirubin as a possible biomarker of PD diagnosis and progression. METHODS: A cross-sectional case-control study was performed to evaluate differences in bilirubin levels between newly diagnosed, drug-naïve PD subjects and controls. Afterwards, PD subjects were included in a 2-year longitudinal study to evaluate disease progression in relation to baseline bilirubin levels. RESULTS: Seventy-five de novo PD subjects were selected and matched with 75 controls by propensity score. Analysis of variance showed higher bilirubin levels in PD patients compared with controls (P < 0.001). Linear regression analysis failed to show a relationship between bilirubin and Unified Parkinson's Disease Rating Scale (UPDRS) part III (P = 0.283) at baseline evaluation. At 2-year follow-up, indirect relationships between bilirubin levels and UPDRS part III (P = 0.028) and between bilirubin levels and levodopa-equivalent daily dosage (P = 0.012) were found. CONCLUSIONS: Parkinson's disease subjects showed higher levels of bilirubin compared with controls. Bilirubin increase might be due to HO overexpression as a compensatory response to oxidative stress occurring from early stages of PD.
BACKGROUND AND PURPOSE: Oxidative stress is a central pathogenic mechanism of Parkinson's disease (PD), and the heme oxygenase (HO) bilirubin pathway is one of the main mammalian antioxidative defences. Indeed, there is growing evidence of HO-bilirubin upregulation from early phases of PD. Our aim was to investigate bilirubin as a possible biomarker of PD diagnosis and progression. METHODS: A cross-sectional case-control study was performed to evaluate differences in bilirubin levels between newly diagnosed, drug-naïve PD subjects and controls. Afterwards, PD subjects were included in a 2-year longitudinal study to evaluate disease progression in relation to baseline bilirubin levels. RESULTS: Seventy-five de novo PD subjects were selected and matched with 75 controls by propensity score. Analysis of variance showed higher bilirubin levels in PDpatients compared with controls (P < 0.001). Linear regression analysis failed to show a relationship between bilirubin and Unified Parkinson's Disease Rating Scale (UPDRS) part III (P = 0.283) at baseline evaluation. At 2-year follow-up, indirect relationships between bilirubin levels and UPDRS part III (P = 0.028) and between bilirubin levels and levodopa-equivalent daily dosage (P = 0.012) were found. CONCLUSIONS:Parkinson's disease subjects showed higher levels of bilirubin compared with controls. Bilirubin increase might be due to HO overexpression as a compensatory response to oxidative stress occurring from early stages of PD.
Authors: Chirag Vasavda; Ruchita Kothari; Adarsha P Malla; Robert Tokhunts; Anthony Lin; Ming Ji; Cristina Ricco; Risheng Xu; Harry G Saavedra; Juan I Sbodio; Adele M Snowman; Lauren Albacarys; Lynda Hester; Thomas W Sedlak; Bindu D Paul; Solomon H Snyder Journal: Cell Chem Biol Date: 2019-07-25 Impact factor: 8.116