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1.
J Environ Sci (China) ; 51: 181-190, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28115129

RESUMO

To evaluate the protective effects of Glycyrrhiza polysaccharide (GPS) against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hepatotoxicity in Jian carp, the fish were fed diets containing GPS at doses of 0.1, 0.5 and 1.0g/kg for 60days before an intraperitoneal injection of 0.6µg/kg TCDD at a volume of 0.05mL/10g body weight. At 72hr post-injection, blood and liver samples were taken for biochemical analysis and the fish liver samples were used for the preparation of pathological slices. The results showed that increases in alanine aminotransferase (GPT), aspartate aminotransferase (GOT), lactate dehydrogenase (LDH), and alkaline phosphatase (AKP) in serum induced by TCDD were significantly inhibited by pre-treatment with 1.0g/kg GPS. Following the 1.0g/kg GPS pre-treatment, total protein (TP), albumin (Alb), catalase (CAT), glutathione peroxidase (GPx), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activities in liver tissue increased significantly, malondialdehyde (MDA) formation (P<0.05 or P<0.01) was significantly inhibited, and the expression of cytochrome P4501A (CYP1A), aryl hydrocarbon receptor 2 (AHR2) and aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) mRNA (P<0.05) was significantly enhanced. Histological observations on fish liver were obtained by preparing paraffin tissue sections via HE staining, and the results showed that histological changes were obviously reduced by 0.5 and 1.0g/kg GPS. GPS significantly reduced liver tissue damage caused by TCDD. Overall, these results proved the hepatoprotective effect of GPS in protecting against fish liver injury induced by TCDD, and supported the use of GPS (1.0g/kg) as a hepatoprotective and antioxidant agent in fish.


Assuntos
Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Glycyrrhiza/química , Dibenzodioxinas Policloradas/toxicidade , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Receptores de Hidrocarboneto Arílico/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Carpas , Catalase/metabolismo , Citocromo P-450 CYP1A1/genética , Glutationa Peroxidase/metabolismo , Fígado/metabolismo , Malondialdeído/metabolismo , Oxirredução , RNA Mensageiro , Receptores de Hidrocarboneto Arílico/genética , Superóxido Dismutase/metabolismo
2.
Mol Autism ; 6: 9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25745553

RESUMO

BACKGROUND: Autism Spectrum Conditions (ASC) are neurodevelopmental conditions characterized by difficulties in communication and social interaction, alongside unusually repetitive behaviours and narrow interests. Asperger Syndrome (AS) is one subgroup of ASC and differs from classic autism in that in AS there is no language or general cognitive delay. Genetic, epigenetic and environmental factors are implicated in ASC and genes involved in neural connectivity and neurodevelopment are good candidates for studying the susceptibility to ASC. The aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) gene encodes a transcription factor involved in neurodevelopmental processes, neuronal connectivity and cellular responses to hypoxia. A mutation in this gene has been identified in individuals with ASC and single nucleotide polymorphisms (SNPs) have been nominally associated with AS and autistic traits in previous studies. METHODS: In this study, we tested 34 SNPs in ARNT2 for association with AS in 118 cases and 412 controls of Caucasian origin. P values were adjusted for multiple comparisons, and linkage disequilibrium (LD) among the SNPs analysed was calculated in our sample. Finally, SNP annotation allowed functional and structural analyses of the genetic variants in ARNT2. We tested the replicability of our result using the genome-wide association studies (GWAS) database of the Psychiatric Genomics Consortium (PGC). RESULTS: We report statistically significant association of rs17225178 with AS. This SNP modifies transcription factor binding sites and regions that regulate the chromatin state in neural cell lines. It is also included in a LD block in our sample, alongside other genetic variants that alter chromatin regulatory regions in neural cells. CONCLUSIONS: These findings demonstrate that rs17225178 in the ARNT2 gene is associated with AS and support previous studies that pointed out an involvement of this gene in the predisposition to ASC.

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