Levodopa on Decrease of Plasma Taurine Level in Parkinsons

Levodopa on Decrease of Plasma Taurine Level in ParkinsonsTitleLevodopa aggravates the decrease of blood blood blood germ plasm taurine take in Parkinson infirmityKey wordsParkinsons disease (PD) Oxidative direction Levodopa perniciousness TaurineHighlightsThis is the premier(prenominal) flying field to explore degenerative use of levodopa on the change of germ plasm taurine take.Plasma taurine take aims were importantly visit in both hardened and untreated PD than in hefty controls.Much lower plasma taurine level was establish in treated PD than the untreated.Plasma taurine level was negatively associated with acac cumulative dosage of levodopa in PD.AbbreviationsPD, Parkinsons disease MMSE, minimental land examination DA, dopamine ROS, reactive oxygen species MAO, monoamine oxidase central nervous system, central nervous ashes H2O2, peroxide SOD, superoxide dismutase CSF, cerebrospinal fluidAbstractIn new years, it has gained more than and more focus that ox idative stress is implicated in the pathophysiology of Parkinsons disease(PD) as well as the potentiality toxicity of levodopa to nigral cells. Also, an increase body of evidence suggests that taurine spiels an important mapping in anti-oxidant function. This say aimed to investigate the relationship mingled with plasma taurine level and clinical variables and the cumulative dosage of levodopa in PD patients. 44 treated patients with PD ( exclusively receive levodopa), 68 untreated patients with PD and 96 age-and sex-matched rubicund controls were recruited. clinical selective information such as age, gender, time, Hoehn and Yahr academic degree and medication memoir were collected. forecast cumulative dosage of levodopa was calculated to indicate the toxicity of chronic inhalation of levodopa. Plasma levels of taurine were measured by HPLC-RF. Plasma taurine levels were meaning(a)ly lower in both treated and untreated PD than ruddy controls. Much lower plasma taurine level was found in treated PD than the untreated. Furthermore, plasma taurine level was negatively associated with cumulative levodopa dosage in PD. Our preliminary study indicates that taurine whitethorn play an important region in pathophysiology of PD and toxicity of chronic levodopa interposition. launchPD is the second most common neurodegenerative disorder characterized by selectively loss of dopamine (DA)-containing neurons in the substantia nigra and a concomitant diminution of DA in the striatum. Levodopa, a natural precursor of DA, has been thegold measurement therapy for PD patients for decades 1. However, thepathophysiology of PD is up to now keep mum poorly understood. more and more focus comes to that oxidative stress is implicated in the pathophysiology of PD, manifested as protein oxidation, lipid peroxidation, DNA oxidation and so on 2. Moreover, in that location has been an increase concern that levodopa may be toxic to dopaminergic neurons 3-5, mainly beca use of its potential to autoxidize from a catechol to a quinine and to generate other forms of reactive oxygen species (ROS) 6.Taurine, an endogenous aminic group acid (2-aminoethanesulfonic acid), is abundant in excitable tissues such as brain, retina, cardiac muscle and skeletal muscle 7. Both in vitro and in vivo studies unneurotic demonstrate that the anti-oxidative activity of taurine is a vital avenue of cytoprotection 8-12. Additionally, our prior(prenominal) study has reported that plasma taurine level was decrease in patients with PD 13. Also, in that location argon lines of evidence that taurine may break cytoprotective effect by acting as a scavenger for libelous free radicals produced by DA or levodopa 14, 15.However, the precise anti-oxidative mechanism of taurine involved in both PD pathophysiology and putative toxicity of levodopa still remains uncertain. Furthermore, few studies turn out been done to address the relationship betwixt plasma taurine level and clinical variables as well as the toxic effects of chronic levodopa administration. Hence, in our study, we specifically explored the be impaction on plasma taurine level because of long-term levodopa intake in PD patients.2. Patients and methods2.1 patientsPatients with PD, diagnosed based on UK Parkinsons disease Brain pious platitude criteria by two movement disorders specialists (Kezhong Zhang and Lian Zhang), were included in this study 16. clinical data were collected by the same medical worker and the Hoehn and Yahr phase angle was used to evaluate the severity of disease 17. Since the anti-parkinsonian drugs may affect plasma taurine level, thorough medication histories were completely obtained through family and patient recall, in the flesh(predicate) medical chart, as well as computerized patient in make-up organisation in our hospital. Exclusion criteria were atypical or secondary Parkinsonism, impaired cognitive status (assessed by the minimental state examination (MMSE) 18), previous neurosurgical treatment for PD, significant laboratory, medical, or psychiatric abnormalities, or any circumstance that might affect plasma taurine level. Age -and gender-matched controls were also recruited, poverty-stricken of neurological disease, poor nutritional status, dementia or a family history of PD. The research project was approved by the ethics committee of the first affiliated hospital of Nanjing medical university and all the participants were given a total explanation and consented to the study in writing.2.2 Calculation of the cumulative levodopa gistIn order to assess the underlying toxicity of levodopa , an approximation of the cumulative levodopa amount was calculated based on the following equation (modified according to that ofNagatsuet al. 19) cumulative levodopa amount g =daily amount of levodopamg * duration of levodopa intake month *30 d/month*0.001g/mg.2.3 measuring stick of taurine levels from plasmaPlasma taurine levels were me asured as previously described 13.2.4 Statistical analysisAll statistical analyses were performed in SPSSV.20.0 (SPSS, Chicago, IL, USA). The newton of the distribution of all continuous variables was examined by ShapiroWilk statistic. Homogeneity of variance was assessed by Levenes test. Group similaritys were made using chi-square test for categorical variables, and one-way ANOVA as well as the Kruskal-Wallis test which was followed by the Mann-Whitney U test with Bonferroni correction for multiple comparisons (controls vs untreated patients, controls vstreated patients, untreated patients vs treated patients), as appropriate, for continuous variables. The correlation significance was evaluated by Spearman rank correlation coefficient.The statistical significance was set at P 3. Results3.1. Demographic data, clinical variables and treatment status of PD Patients and ControlsThe demographic and clinical data of all subjects are summarized in Table 1. Gender and age did non diff er among triad groups, while the duration was longer (2.901.50vs. 1.451.14y, pHoehn and Yahr stage was higher (1.970.71vs. 1.670.72, pdetailed information on the treatment status see Table 2).3.2. Plasma taurine level in PD patients and controlsNotably, both treated PD (41.1622.72mol/L) and untreated PD (57.3831.05mol/L) were found to have significantly decreased plasma taurine levels compared to healthy controls (133.8345.91mol/L, P for both comparisons for the two PD groups were considered as a whole, the mean taurine level was also significantly lower than that in the control group (P3.3. Association between plasma taurine level and clinical variables and treatment status.Plasma taurine levels showed, however, no statistically significant association with age, duration, as well as Hoehn and Yahr stage in treated PD, untreated PD or all patients (Data not show). Interestingly, significant correlation was found between taurine level and cumulative levodopa dosage (shown in Fig.2, rs =-0.351, PDiscussionAccording to our knowledge, this is the first study to explore chronic use of levodopa on the change of plasma taurine level. The major endings of this study are summarized as follows 1) Treated and untreated PD were found to have significantly decreased plasma taurine levels compared to healthy controls. 2) Plasma taurine level was lower in treated PD than the untreated, and inversely correlated with cumulative dosage of levodopa.Taurine, the most abundant amino acid in mammals, is widely distributed in central nervous establishment (CNS) 20 and its biosynthesis mainly takes place in the liver 21. In the CNS, the tightness of taurine is dependent on food and a complex run system at the blood brain barrier 20. Hence, plasma taurine may partially reflect the pathological change in CNS of PD patients.Firstly, decreased plasma taurine level of patients with PD discovered in this study is in line with our previous work 13. Similarly, there have been some stud ies reporting CSF (cerebrospinal fluid) taurine level was significantly decreased in PD when compared to healthy controls 19, 22. Previous studies provide evidence that taurine has a remarkable anti-oxidative function. Furthermore, in a study of PC12 cells, taurine exhibited a protective single-valued function against oxidative stress generate by peroxide (H2O2) through the alleviation of endoplasmic reticulum stress 12. Also, Castro-Caldas et al. 10 reported that pretreatment of TUDCA (an analogue of taurine) abrogated the level of ROS in MPTP-mice, thus come along highlighting the anti-oxidative role in vivo and suggesting that TUDCA may modulate the intracellular oxidative environment via interfering with the cellular oxidation-reduction threshold. Moreover, it has been observed that significant increases in glutathione content and superoxide dismutase (SOD) activity were founded in the livers of the taurine-supplemented 6-OHDAinduced PD rats, which indicated that taurine may increase the defenses against oxidative spite 11. Collectively, we assume that the decrease of plasma taurine level may result from chronic assumption of oxidants. Therefore, taurine may play an important neuroprotective role in the pathophysiology of PD via its potent anti-oxidative activity.By contrast, both normal 23 and increase 24-26 CSF taurine levels were found in several previous studies. Moreover, no significant decreased plasma taurine was observed in Molina et al.s study 22. However, studies conductedby Lakke et al. 25, 26, Tohgi et al. 23 and Araki et al. 24 all had some limitations. For example, the controls were not well matched regarding gender and age. Additionally, different sample sizes and measurements may also partially explain the discrepancy of the results. Compared with those previous studies, we recruited relatively more patients in this study. Also, statistical analysis was well performed and measurement used in our study is more stable and sensitive.Neve rtheless, we fail to observe correlation between plasma taurine level and age, duration and Hoehn and Yahr in treated PD, untreated PD or all PD. This may result from that only patients with relatively short duration (within 5 years) and low Hoehn and Yahr (within stage 3) were enrolled in our study, and the plasma taurine was probably not sensitive enough to examine the underlying correlation in early to medium stage PD patients. Therefore, further research including more stages of patients would bring more invaluable information on this point.Secondly, treated PD patients exhibited lower plasma taurine level than the untreated. Although the duration was longer and the Hoehn and Yahr stage was higher in treated PD than untreated PD, neither of the two clinical variables was correlated with plasma taurine level in each group. More importantly, plasma taurine level significantly negatively correlated with cumulative dosage of levodopa. These data suggest that chronic treatment of lev odopa may affect plasma taurine concentration.Previous studies have shown that levodopa has the capacity to form ROS by autoxidation from catechols to quinines 4. Interestingly, Biasetti et al. 27 found that taurine attenuated iron-catalyzed quinine formation from levodopa. Also, some studies suggest that taurine may bind these toxic quinones 27, 28. Furthermore, there have been studies 29 showing that chronic systemic administration of levodopa to rodents depleted taurine pools, suggesting that taurine might play an important role in scavenging oxidants derived from levodopa metabolism in vivo. Therefore, we suppose that chronic consumption of taurine due to oxidants induced by levodopa may partially explain lower plasma taurine level in levodopa-treated PD than the untreated.However, there were different results observed in some other studies. Molina et al. 22 reported that no significant difference of CSF taurine level was found between levodopa-treated PD (n=21) and non-levedop a-treated PD (including untreated PD, n=8). The relatively small sample size may limit its interpretation. Moreover, Diederich et al. 30 found no significant decrease of plasma taurine after intense administration of levodopa. However, the acute levodopa administration may not fully refect the toxicity of cumulative levodopa intake.Nevertheless, our study has some limitations. Firstly, the population in this study is relatively small and the results must be interpreted cautiously. Secondly, as this is only a retrospective study, future longitudinal study combining with biomarkers of oxidative stress will provide more important information on the role of levodopa in affecting the plasma taurine level as a neurotixic agent and of taurine as a anti-oxidative agent.In conclusion, our results showed that decreased plasma taurine level was found in patients with PD in comparison to healthy controls. Moreover, plasma taurine level was found lowed in treated PD than the untreated, and inve rsely correlated with cumulative levodopa dosage. Combining with previous studies, these data suggest taurine may play an important protective role in pathophysiology of PD and chronic administration of levodopa may have potential neurotoxicity by depleting taurine. Also, our pilot study could, at least, provide new insights into curative strategies.