RESUMEN
Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder characterized by the accumulation of accumulated alpha-synuclein (α-Syn) in substantia nigra. Research has shown that selenium (Se) can protect neural cells through the actions of selenoproteins, including selenoprotein P (SelP) and selenoprotein S (SelS), which participate in endoplasmic reticulum-associated protein degradation (ERAD). In this study, we investigated the potential protective role of Se in a pre-clinical PD rat model.We aimed to evaluate the therapeutic effects of Se administration in the 6-hydroxydopamine (6-OHDA) induced unilateral rat PD model. Male Wistar rats were utilised for unilateral PD animal model which were subjected to stereotaxic surgery and injected with 20 µg 6-OHDA/5 µl 0.2% ascorbate saline. After confirming the model, the rats were intraperitoneally injected with 0.1, 0.2, and 0.3 mg/kg of sodium selenite for 7 days. We then performed behavioral tests, including apomorphine-induced rotation, hanging, and rotarod tests. Following sacrifice, we analysed the substantia nigra area of the brain and serum for protein quantification, element analysis, and gene expression analysis.Our results indicate that the administration of 0.3 mg/kg of Se improved the motor deficiency in hanging, rotarod, and apomorphine-induced rotational tests. While there was no significant improvement in the expression of α-Syn, Se increased the expression of selenoproteins. Additionally, levels of selenoproteins, Se, and α-Syn both brain and serum were re-established by the treatment, suggesting the role of Se on the α-Syn accumulation. Furthermore, Se improved PD-induced biochemical deficits by increasing the levels of SelS and SelP (p<0.005).In conclusion, our findings suggest that Se may have a protective role in PD. 0.3 mg/kg dosage of Se increased the expression of selenoproteins, reduced the accumulation of α-Syn in the brain, and improved PD-induced motor deficits. These results suggest that Se may be a potential therapeutic option for PD treatment.
Asunto(s)
Enfermedad de Parkinson , Selenio , Ratas , Masculino , Animales , Enfermedad de Parkinson/tratamiento farmacológico , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , alfa-Sinucleína/uso terapéutico , Porción Compacta de la Sustancia Negra/metabolismo , Selenio/metabolismo , Apomorfina/metabolismo , Apomorfina/uso terapéutico , Oxidopamina/farmacología , Oxidopamina/metabolismo , Oxidopamina/uso terapéutico , Ratas Wistar , Selenoproteínas/metabolismo , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: While Parkinson's disease (PD) etiology is not clear yet, accumulated alpha-synuclein is proposed to induce neurodegeneration. Selenium (Se) and its functional proteins play a key role in aggregation of misfolded proteins. However, their implications in neurodegenerative process are unclear. AIM: Diagnosing Se and selenoprotein P (SelP), selenoprotein S (SelS) proportions in serum of PD patients to compare with healthy controls, whether the changes in their concentration could be a biomarker for PD. METHODS: Se concentration was investigated in 30 PD patients and 30 controls using atomic absorption spectrometry. Also, alpha-Synuclein, SelP, and SelS levels were evaluated by ELISA. The parameters were compared in PD patients and controls. Also, the variations within the case group according to their age, disorder stage, and drug administration were evaluated. RESULTS: PD subjects had higher Se concentration. The mean SelP in PD patients was lower from controls, whilst SelS levels were higher. Also, the concentration of alpha-synuclein was higher in PD patients. However, age, stage (except UPDRS III), and disorder duration had no influence on the Se and selenoproteins level, whilst there was a direct association between alpha-synuclein levels and disorder stage. Also, alpha-synuclein proportions in subjects using levodopa was significantly higher. CONCLUSION: Our results suggest that serum levels of Se and SelP could be a biomarker or risk factor for PD. Although SelS interferes to reduce aggregated proteins, its pathway in PD is not clearly understood. Future studies could focus on how SelS can reduce on alpha-synuclein aggregation. Thus, other studies should be performed on this issue to induce the selenoproteins in PD.
Asunto(s)
Enfermedad de Parkinson , Selenio , Humanos , alfa-Sinucleína , Biomarcadores , Selenoproteína P , Selenoproteínas/metabolismoRESUMEN
AIM: Parkinson disease (PD) is a prevalent central nervous system degenerative condition that impacts elderly people. Recent clinical and experimental study findings have established oxidative stress as one of the main pathogeneses of PD. Selenium, a trace metals with antioxidant effects, might reverse the neurobehavioral impairments and oxidative stress in rats. Thus, the goal of this study was to ascertain if Selenium Nano Particles (SeNPs) are also effective to protect brain cells from oxidative stress or not. MAIN METHODS: SeNPs were synthesized utilizing Ascorbic acid and chitosan as a reducing and stabilizing agent. Next, eight groups (N: 6) of male Wistar rats were randomly assigned and injected by different dosage (0.1, 0,2, and 0.3 mg/kg) of Se and SeNP. Finally, to ascertain the protective benefits of SeNP on PD rats, behavioral evaluation, clinical symptoms, antioxidant activity, and oxidant levels were examined. KEY FINDINGS: According to the findings, PD rats' motor functions had developed by SeNP injection. Higher MDA levels and inhibited antioxidant activities (SOD, CAT, and GPX) in lesion group are highlighting the significant role of oxidative stress in dopaminergic neuron death and neurobehavioral abnormalities. SeNP also protect against oxidative stress as compared to the lesion group. The levels of MDA had greatly reduced while the activities of enzymes, TAC, and SeNP both had significantly increased. SIGNIFICANCE: By enhancing antioxidant activity, administration of SeNP can reduce the hazardous consequences of oxidative stress.
Asunto(s)
Nanopartículas , Enfermedad de Parkinson , Selenio , Ratas , Masculino , Animales , Selenio/farmacología , Selenio/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Ratas Wistar , Estrés Oxidativo , Encéfalo/metabolismoRESUMEN
Gastric cancer is one of the most prevalent cancers in northern Iran. The DNA repair genes X-ray repair cross-complementing (XRCC) group 5, XRCC6, which are important members of non-homologous end-joining repair system, play an important role in repairing the DNA double-strand breaks. Chronic exposure to heavy metals has long been recognized as being capable of augmenting gastric cancer incidence among exposed human populations. Since trace elements could directly or indirectly damage DNA, and polymorphism in DNA DSBs-repair genes can alter the capacity of system repair, we assumed that XRCC5 VNTR and XRCC6-61C >G polymorphism also impress the DSBs-repair system ability and contribute to gastric cancer. Therefore, the objective of this research was to evaluate the tissue accumulation of Selenium (Se), Cadmium (Cd) and Arsenic (As), and XRCC5 VNTR, XRCC6-61C >G polymorphisms in cancerous and non-cancerous tissues in Golestan province. The study population included 46 gastric cancer patients and 43 cancer-free controls. Two polymorphisms of XRCC5, XRCC6 were genotyped using polymerase chain reaction (PCR) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Further employed was atomic absorption spectroscopy so as to determine the levels of Se, Cd and As. Finally, the data were analyzed by SPSS (version 16) statistical software. The Se level was significantly higher in tumors as compared to non-tumor tissues, but there was no significant correlation between As and Cd in cancerous and noncancerous tissues. Allele frequencies of the selected genes were not statistically different between groups regarding XRCC6 (-61C>G). XRCC5 0R/0R, 0R/1R, 1R/1R, and 0R/2R genotypes were more common in cancerous group. High levels of Se in cancerous tissues vs. non-cancerous tissues may be one of the carcinogenic factors; in Golestan province, unlike other regions of Iran and the world, the level of Se is high, hence the higher risks of gastric cancer.
Asunto(s)
Arsénico/análisis , Cadmio/análisis , Reparación del ADN/genética , Autoantígeno Ku/genética , Polimorfismo de Nucleótido Simple/genética , Selenio/análisis , Neoplasias Gástricas/genética , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , Femenino , Perfilación de la Expresión Génica , Genotipo , Humanos , Irán , Masculino , Persona de Mediana EdadRESUMEN
Fetuin-A, a hepatic glycoprotein present in the circulation, is a potential inhibitor for systemic calcification. The main aim of this study was to evaluate the association between fetuin-A and other biochemical parameters as facilitator factors for developing atherosclerosis in hemodialysis (HD) patients. This case-control study was conducted on 44 HD patients undergoing treatment in 2012. Parathormone (i-PTH) and fetuin levels were performed by the enzyme-linked immunosorbent assay method, high-sensitivity C-reactive protein (hs-CRP) by chemiluminescence, low-density lipoprotein by direct enzymatic, calcium and albumin by colorimetric and phosphorous by ultraviolet (UV) methods. Chi-square was used for evaluating the association between variables and t-test was used for comparing the mean of the quantitative variables for the two groups. SPSS-16 software was used for data analysis and P-value less than 5% was considered as significant. Mean of serum fetuin level was 23.25 ± 4.90 ng/mL in HD patients and 32.92 ± 5.21 in the control group. Median of hs-CRP was 2.45 mg/dL in the patients and 1.00 mg/dL in the control group and i-PTH was 74.3 pg/mL in the patients and 7.30 pg/mL in the control group. The calcium-phosphorous product was 46.77 ± 14.22 mg/dL in the patient and 31.73 ± 6.48 mg/dL in the control group. A reverse significant association was found between fetuin-A and hs-CRP in this study. In this study, serum fetuin-A level in HD patients was lower than controls. Therefore, a low level of fetuin-A seems to be associated with atherosclerosis, inflammation and malnutrition.
Asunto(s)
Aterosclerosis/sangre , Aterosclerosis/etiología , Diálisis Renal/efectos adversos , alfa-2-Glicoproteína-HS/análisis , Adulto , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Calcio/sangre , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Colorimetría , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inflamación/sangre , Inflamación/etiología , Modelos Logísticos , Masculino , Desnutrición/sangre , Desnutrición/etiología , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Fósforo/sangre , Medición de Riesgo , Factores de Riesgo , Albúmina Sérica/análisis , Albúmina Sérica Humana , Espectrofotometría Ultravioleta , Resultado del TratamientoRESUMEN
Chronic renal disorders have a progressive course in most cases, and finally result in end-stage renal disease (ESRD). Hemodialysis (HD) is one of the mainstays in the treatment of these patients. Disturbance in calcium (Ca) and phosphorus (P) metabolism and alteration of serum levels of parathormone (PTH) are observed in these patients. One of the most common cutaneous manifestations in patients on HD is pruritus. The aim of this study is to evaluate the association between pruritus and serum concentrations of Ca, P and PTH in patients with chronic renal disease. This analytic, descriptive, cross-sectional study was performed on 120 patients on HD at the Fifth-Azar Hospital in Gorgan, Iran, in 2010. Information related to the patients, including age, gender, pruritus, time of pruritus and duration on dialysis, was extracted from questionnaires. Serum concentrations of intact PTH, Ca and P were measured. Data were analyzed by the chi-square test and SPSS-16 software. A P-value less than 0.05 was considered statistically significant. Among the 120 study patients, 50% were male and the mean age (±SD) was 49 ± 12.3 years. Sixty percent of the patients had pruritus, of whom 33.3% had PTH levels above the normal range. Among the 40% of the patients who did not have pruritus, 39.6% had PTH levels higher than the normal levels. The mean serum Ca and P levels were 8.44 ± 1.65 mg/dL and 5.48 ± 1.81 mg/dL, respectively. The mean (±SD) Ca-P product was 55.46 ± 47.16 and the mean PTH concentration was 274.34 ± 286.53 pg/mL. No significant association was found between pruritus and age, sex, serum PTH and P levels as well as Ca-P product. However, the association between serum Ca levels and pruritus was significant (P = 0.03). Our study showed that most patients with pruritus had serum Ca levels in the abnormal range (lower or higher), and there was no significant correlation between serum iPTH level and pruritis. Thus, good control of serum Ca levels is important to reduce pruritus in these patients.