Serum uric acid levels in patients with Parkinson's disease: Their relationship to treatment and disease duration

Abstract

There is evidence to support that oxidative stress is increased in Parkinson's disease (PD) and contributes to degeneration of dopaminergic neurons. Uric acid (UA), a natural antioxidant in blood and brain tissue, scavenging superoxide, peroxynitrite and hydroxyl radical, was found reduced in the serum of PD patients. In addition low plasma uric acid (UA) levels have been associated with an increased risk of PD.

Objectives

The aim of our study was to investigate serum UA levels in PD patients compared with age-matched healthy controls and their possible relationship with several clinical parameters of PD and pharmaceutical treatment.

Patients and methods

We measured serum UA levels in 43 PD patients and 47 healthy volunteers, age and sex-matched. UA levels were correlated with disease duration, severity and treatment.

Results

Low UA levels were observed in PD patients compared with controls (p = 0.009). Age, Body Mass Index (BMI) and UPDRS III score did not significantly affect serum UA concentrations, whereas gender was found to contribute significantly to UA level (p < 0.000). Strong and significant inverse correlations of UA with disease duration (R_s = −0.397, p = 0.009) and daily levodopa dosage (R_p = −0.498, p = 0.026) were observed. These associations were significant for men (R_s = −0.441, p = 0.04 and R_s = −0.717, p = 0.03 respectively), but not for women (R_s = −0.221, p = 0.337 and R_s = −0.17, p = 0.966 respectively).

Conclusion

Our results suggest that there may be increased consumption of UA as a scavenger in PD, possibly heightened by dopaminergic drug treatment. Given the antioxidant properties of UA, manipulation of its concentrations should be investigated for potential therapeutic strategies of the disease.

Introduction

Oxidative stress in the brain has been implicated as playing a role in the onset of Parkinson's disease (PD) and leads to an increase in oxidative damage in the substantia nigra, manifested as lipid peroxidation, protein oxidation and DNA oxidation [1]. Such damage is probably mediated through the toxic actions of nitrite oxide (NO) that is involved in the formation of oxidizing species such as peroxynitrite and is accumulated over time possibly contributing to nigral cell degeneration [1], [2], [3]. PD patients are found to have decreased antioxidant defences of cells that render them susceptible to damage from reactive oxygen (ROS) and nitrogen species (RNOS) and others formed during cell metabolism and oxidative stress [4], [5].

Uric acid (UA) is known to be an important natural antioxidant in blood and brain tissue, scavenging superoxide, peroxynitrite and hydroxyl radical [3]. It has been shown to inhibit free radical-initiated lipid peroxidation and DNA damage [6]. In addition, it forms strong complexes with iron, particularly Fe3+ [7] which may contribute to oxidative damage in PD by promoting the formation of the highly reactive hydroxyl free radical [8]. Moreover, uric acid has been shown to slow dopamine (DA) auto-oxidation rate in caudate and substantia nigra homogenates of parkinsonian patients [9]. Any loss of this purine metabolite could result in a diminished free antioxidant capacity. The decreased levels of UA observed in nigrostriatal human dopamine neurons [9] may contribute to an environment susceptible to oxidative stress, as suggested by the findings of suppression of oxidative stress and prevention of dopaminergic cell death in animal models of PD with the administration of UA [10]. Since DA oxidation and the consequent generation of reactive oxygen species (ROS) may contribute to the degeneration of dopaminergic neurons, UA may play an important protective role.

Higher serum uric acid levels have been associated with a significantly reduced risk of PD, with evidence for a dose–effect relationship, implying that reduced UA concentrations may have a causal role in PD [11], [12], [13], [14], [15], [16], [17]. Moreover lower plasma UA levels were found in treated PD patients compared to healthy controls [18]. In addition among untreated patients with early PD, higher plasma UA concentrations were associated with a slower rate of clinical progression [19]. Several of these studies include only men [11], [13], [15]. Conflicting results concerning the association of low serum UA levels with either the risk or the progression of PD have been reported in those studies comprising both males and females [12], [14], [16], [17], [18], [19]. Some report that this correlation is significant only for men [14], [17], [19], whereas others did not found any gender differences [12], [16], [18].

Thus, the aim of the present study was to investigate serum uric acid levels in PD patients compared with age matched healthy controls, their possible relationship with several clinical parameters of PD and the existence of any difference between sexes. Given that additional oxidative stress in PD may be induced by l-dopa treatment, we divided our patients into two subgroups (treated and untreated) to investigate the effect of dopaminergic treatment on serum UA concentration.