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6-Hydroxydopamine (6-OHDA) selectively enters dopaminergic neurons and undergoes auto-oxidation resulting in the generation of reactive oxygen species and dopamine quinones, subsequently leading to apoptosis. This mechanism mimics the pathogenesis of Parkinson's disease and has been used to induce experimental Parkinsonism in both in vitro and in vivo systems. In this study, we investigated the effects of curcumin I (diferuloylmethane) purified from Curcuma longa on quinoprotein production, phosphorylation of p38 MAPK (p-p38), and caspase-3 activation in 6-OHDA-treated SH-SY5Y dopaminergic cells. Pretreatment of SH-SY5Y with curcumin I at concentrations of 1, 5, 10, and 20 μM, significantly decreased the formation of quinoprotein and reduced the levels of p-p38 and cleaved caspase-3 in a dose-dependent manner. Moreover, the levels of the dopaminergic neuron marker, phospho-tyrosine hydroxylase (p-TH), were also dose-dependently increased upon treatment with curcumin I. Our results clearly demonstrated that curcumin I protects neurons against oxidative damage, as shown by attenuation of p-p38 expression, caspase-3-activation, and toxic quinoprotein formation, together with the restoration of p-TH levels. This study provides evidence for the therapeutic potential of curcumin I in the chemoprevention of oxidative stress-related neurodegeneration. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim: To compare levels of lipid peroxidation and antioxidants in synovial fluid from primary knee osteoarthritis (OA) patients with severe cartilage damage undergoing total knee replacement with those in the synovial fluid from injured knee joint patients with intact cartilage undergoing knee arthroscopy. Methods: Thirty-two OA patients and 10 injured knee joint patients were recruited. Lipid peroxidation (thiobarbituric acid reactive substances [TBARs]), iron and glutathione (GSH) were measured using a colorimetric method. Vitamin E was measured with high-performance liquid chromatography (HPLC). Activities of antioxidant enzymes (glutathione peroxidase [GPx], superoxide dismutase [SOD]) were analyzed with the use of a kinetic method. Results: TBARs, iron and GSH levels in synovial fluid were not significantly different between OA patients and injured knee joint patients. Antioxidant enzymes such as GPx and SOD activities also indicated no significant difference. Only vitamin E level was significantly lower in the synovial fluid of OA patients than in that of the injured knee joint patients. Conclusions: Oxidative stress may have a role in pathogenesis of knee osteoarthritis. Vitamin E supplementation may have a role in the management of patients. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • UGT1A6 has been proposed as the predominant isoform responsible for the glucuronidation of deferiprone. • UGT1A6* 2 allele has been associated with the altered enzyme activity. WHAT THIS STUDY ADDS • There is no statistically significant effect of UGT1A6 genotype on the single-dose pharmacokinetics of deferiprone in healthy volunteers. • Gender influences serum pharmacokinetics of deferiprone. • Body iron stores reflected by serum ferritin levels may have an influence on the extent of extravascular deferiprone distribution. AIMS To examine the effects of UGT1A6 polymorphisms on the pharmacokinetics of deferiprone in healthy volunteers. METHODS Twenty-two healthy volunteers were enrolled and grouped according to UGT1A6 genotype. After an overnight fast, the subjects received a single oral dose of 25 mg kg−1 deferiprone. Blood samples were collected at 0, 15, 30, 45, 60, 90, 120, 180, 240, 300 and 360 min after dosing. Urine output was collected at 0, 0–2, 2–4, 4–8, 8–12 and 12–24 h. Deferiprone (L1) and deferiprone-glucuronide (L1G) concentrations in serum and urine were determined using a validated high-performance liquid chromatography method. UGT1A6 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS No statistically significant differences in any pharmacokinetic parameters of either deferiprone or deferiprone-glucuronide among the genotype groups were noted. Likewise, there were no statistically significant differences in 24-h urinary deferiprone and deferiprone-glucuronide excretion among the genotype groups. Significant differences between men and women were found in AUC0–∞, Vd/ F, and CL/ F of deferiprone. Gender differences in 24-h urinary deferiprone and its metabolite excretion, however, failed to reach statistical significance. The Vd/ F of deferiprone was found to correlate significantly with serum ferritin ( rs = 0.665; P = 0.001). CONCLUSION The studied single nucleotide polymorphisms in UGT1A6 do not appear to exert statistically significant effects on the single-dose pharmacokinetics of deferiprone. Gender appears to influence the serum pharmacokinetics of deferiprone, but not urinary excretion of deferiprone and its metabolite. Body iron stores may have an influence on the extent of extravascular deferiprone distribution. [ABSTRACT FROM AUTHOR]

Background and objectives:  Cholelithiasis has been observed with high incidence in beta-thalassemia/hemoglobin E (β-thal/Hb E). Recent studies have shown that a variant TATA-box in the promoter region of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene is associated with the development of cholelithiasis. The coding region mutation (G71R) of the UGT1A1 gene was higher in Asians than those in Caucasians. The relationship between the variant UGT1A1 promoter and coding region gene and cholelithiasis in β-thal/Hb E subjects were investigated. Methods:  One hundred and seventeen β-thal/Hb E subjects entered this study. The TATA-box and G71R mutations were analyzed by fragment size analysis and restriction fragment length polymorphism methods, respectively. Results:  The incidence of cholelithiasis was higher in heterozygous (68.3%) and homozygous (100%) subjects compared with normal UGT1A1 haplotype (61.4%). Total bilirubin level (6.0 ± 2.03 mg/dL) in the homozygous group was significantly higher than that of wild type (3.31 ± 1.83 ng/dL). Prevalence of cholelithiasis increased with age (OR = 1.1, 95% CI = 1.03–1.12, P < 0.001). Female gender (OR = 3.7, 95% CI = 1.3–10.6, P < 0.01) and elevated liver enzyme (OR = 1.02, 95%CI = 1.0–1.04, P < 0.02) were two other risk factors for cholethiasis in β-thal/Hb E. Conclusion:  This study shows that the combined TATA-box variants and G71R mutations of the UGT1A1 is associated with cholelithiasis in β-thal/Hb E. [ABSTRACT FROM AUTHOR]