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

Qin, Xiaoling; Zhang, Qingshan; Sun, Li; Hao, Mengwei; Hu, Zhongyang

doi:10.1007/s12013-014-0402-x

Cited by 22 publications

(24 citation statements)

References 34 publications

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“…Case-control studies have consistently shown lower urate in subjects with PD compared to controls. Qin et al compared bilirubin and urate levels in 425 PD patients and 460 controls and found lower urate levels in PD compared to controls (p<0.0001) (186). Sakuta et al evaluated serum urate levels in 100 patients with PD, 42 patients with MSA, 30 patients with PSP, and 100 controls.…”

Section: Urate and Pd Riskmentioning

confidence: 99%

Targeting urate to reduce oxidative stress in Parkinson disease

Crotty

Ascherio

Schwarzschild

2017

Experimental Neurology

112

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Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and for improving study designs to test for disease modification by antioxidants. Urate, the main antioxidant found in plasma as well as the end product of purine metabolism in humans, has emerged as a promising potential neuroprotectant with advantages that distinguish it from previously tested antioxidant agents. Uniquely, higher urate levels in plasma or cerebrospinal fluid (CSF) have been linked to both a lower risk of developing PD and to a slower rate of its subsequent progression in numerous large prospective epidemiological and clinical cohorts. Laboratory evidence that urate confers neuroprotection in cellular and animal models of PD, possibly via the Nrf2 antioxidant response pathway, further strengthened its candidacy for rapid clinical translation. An early phase trial of the urate precursor inosine demonstrated its capacity to safely produce well tolerated, long-term elevation of plasma and CSF urate in early PD, supporting a phase 3 trial now underway to determine whether oral inosine dosed to elevate urate to concentrations predictive of favorable prognosis in PD slows clinical decline in people recently diagnosed, dopamine transporter-deficient PD.

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Section: Urate and Pd Riskmentioning

confidence: 99%

Targeting urate to reduce oxidative stress in Parkinson disease

Crotty

Ascherio

Schwarzschild

2017

Experimental Neurology

112

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“…Bilirubin is an important natural antioxidant in the human body and is a major contributor to the total antioxidant capacity of plasma [4]. Several previous studies have found that bilirubin is possibly a marker altering the risk of PD [5][6][7]. To our knowledge, no study has examined the association between bilirubin and motor subtypes of PD.…”

Section: Introductionmentioning

confidence: 98%

Association of Serum Indirect Bilirubin Concentrations with Motor Subtypes of Parkinson’s Disease

Zhao

Zhong

et al. 2019

Neurodegener Dis

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Introduction: We aimed to investigate the change of serum indirect bilirubin (IBIL) concentrations in patients with Parkinson's disease (PD) and whether IBIL concentrations were associated with the motor subtypes of PD. Methods: A casecontrol study was performed to evaluate differences in bilirubin concentrations between 78 PD subjects and 78 controls. Venous blood samples were collected, and total bilirubin (TBIL), direct bilirubin (DBIL), and IBIL concentrations were analyzed between PD subjects and controls. PD patients were classified into three motor subtypes: tremordominant (TD), intermediate (I), and postural instability and gait disorder (PIGD). It was evaluated whether there were differences in IBIL concentrations between the different motor subtypes and between motor subtypes and controls. Results: PD patients had lower IBIL concentrations compared to controls (6.51 ± 4.03 vs. 10.82 ± 4.61, p < 0.001). There was no significant difference in IBIL concentrations between PD males and PD females (6.66 ± 3.64 vs. 6.22 ± 4.79, p = 0.655).IBIL concentrations had negative relationships with levodopa-equivalent daily dose (LEDD) (R = -0.452, p < 0.001) and positive relationships with tremor score (R = 0.360, p = 0.001). IBIL concentrations were significantly lower for PIGD than for TD subtype (4.88 ± 4.03 vs. 9.00 ± 4.15, p < 0.001). The lower IBIL concentrations in PD compared to controls were mainly driven by the PIGD patients. Conclusions: PD subjects showed lower levels of IBIL compared to controls. Higher IBIL levels were associated with TD motor subtype in PD, which could be related to the antioxidative properties of IBIL.

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“…Recently, the association between serum urate levels and PD has gained intensive interests, but results of these studies have been inconsistent. Some studies have shown a clear trend of lower serum urate levels in PD and subgroups based on sex [9–17], while others showed no significant variation of lower serum urate levels in PD [18–23]. Our previous studies showed that the serum UA levels in PD patients were significantly lower than sex and age-matched healthy controls and the UA concentrations were decreased with the deterioration of the illness[24].…”

Section: Introductionmentioning

confidence: 99%

Serum uric acid levels in patients with Parkinson’s disease: A meta-analysis

et al. 2017

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BackgroundLower serum uric acid (UA) levels have been reported as a risk factor in Parkinson’s disease (PD). However, the results have been inconsistent so far.ObjectivesThe aim of the present study was to clarify the potential relationship of uric acid with PD.MethodsComprehensive electronic search in pubmed, web of science, and the Cochrane Library database to find original articles about the association between PD and serum uric acid levels published before Dec 2015. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using I2 and H2 statistics. Sensitivity analyses to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger’s regression test. Analyses were performed by using Review Manager 5.3 and Stata 11.0.ResultsThirteen studies with a total of 4646 participants (2379 PD patients and 2267 controls) were included in this meta-analysis. The current results showed that the serum UA levels in PD patients were significantly lower compared to sex and age-matched healthy controls (SMD: -0.49, 95% CI: [-0.67, -0.30], Z = 5.20, P < 0.001) and these results showed no geographic regional (Asia: SMD = −0.65, 95% CI [−0.84, −0.46], Z = 6.75, p <0.001; Non-Asia: SMD = −0.25, 95% CI [−0.43, −0.07], Z = 2.70, p = 0.007) and sex differences (women: SMD = −0.53, 95% CI [−0.70, −0.35], z = 5.98, p <0.001; men: SMD = −0.66, 95% CI [−0.87, −0.44], z = 6.03, p <0.001). Serum UA levels in middle-late stage PD patients with higher H&Y scales were significantly lower than early stage PD patients with lower H&Y scales (SMD = 0.63, 95% CI [0.36,0.89], z = 4.64, p <0.001).ConclusionsOur study showed that the serum UA levels are significantly lower in PD and the level is further decreased as the disease progresses. Thus it might be a potential biomarker to indicate the risk and progression of PD.

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

Cited by 22 publications

References 34 publications

Targeting urate to reduce oxidative stress in Parkinson disease

Targeting urate to reduce oxidative stress in Parkinson disease

Association of Serum Indirect Bilirubin Concentrations with Motor Subtypes of Parkinson’s Disease

Serum uric acid levels in patients with Parkinson’s disease: A meta-analysis

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